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PMC7710430_01 | Male | 41 | A previously healthy 41-year-old male, with no known cardiovascular risk factors, attended the emergency department with painless horizontal binocular diplopia which had started 12 hours earlier. Three days prior to the onset of symptoms, the patient had been started on ciprofloxacin for a complicated urinary tract infection. The neuroophthalmologic examination was remarkable for the presence of horizontal binocular diplopia on leftward gaze. Visual acuity was 20/16 oculus uterque (OU) without correction. Intraocular tension was 12 mmHg OU. Slit lamp examination and fundoscopy were within normal limits OU. On the Hess-Weiss testing, we identified diminished function of the left lateral rectus muscle and an associated increased compensatory function of the right medial rectus muscle, confirming a paresis of the left lateral rectus muscle (Figure 1). The rest of the physical examination was unremarkable.
Blood tests revealed a slightly increased CRP without leukocytosis. TSH was normal. Cerebral imaging (MRI and CT-angiography) and orbital MRI results were within normal limits. Analysis of cerebrospinal fluid was normal. Serology tests (HIV, syphilis, Lyme disease, and TBE) were negative. Taken together, we concluded on a probable fluoroquinolone-induced unilateral tendinopathy of the left abducens muscle. Ciprofloxacin was stopped and replaced by coamoxicillin. The patient reported progressive regression of diplopia after withdrawal of ciprofloxacin. At a follow-up consultation one week after ciprofloxacin withdrawal, the patient's symptoms had fully resolved. Three months later, the Hess-Weiss testing showed a complete recovery (Figure 2). | null | Not supported with pagination yet | null |
PMC3168040_01 | Male | 20 | A 20-year-old male, truck driver, presented with a primary complaint of genital swelling developed over the last six months. He also had concomitant bizarre and protean skin lesions over lower abdomen, face, neck and thighs along with discharging lesion over right axilla. He gave a history of lesions over face appearing first and other lesions presenting slowly over two years, all with centrifugal expansion. The genital swelling was associated with recent onset pain and itching. The patient had a history of multiple sexual exposures. There was no history of discharge per urethra, genital ulcer or trauma. He also had history of antituberculous and antifilarial treatment with no alleviation of symptoms.
Examination revealed pallor and generalized lymphadenpathy. The patient had grotesque swelling over scrotum and penis [Figure 1a]. There were multiple, well defined large plaques with warty surface over lower abdomen, encircling the upper medial and posterior thighs, superimposed with crusting and discharge [Figure 1a]. Similar warty papules were seen over forehead and neck with satellite lesions peripherally and a discharging sinus over left axillary region [Figure 2a].
The differential diagnosis of cutaneous tuberculosis, bacterial STI with complications, filariasis and immunosuppression associated symptoms were kept. Hematological investigations, FNAC, chest X-ray, and USG abdomen were done- all of which were normal. Serum HIV, VDRL with titre were non reactive. The case was reanalyzed and subjected to surgical biopsy to evaluate for less considered diagnosis of chromoblastomycosis in case of genital elephantiasis. Biopsy was suggestive of foreign body granuloma showing muriform body; pseudo epitheliomatous hyperplasias of the epidermis and on staining, fungal hyphae were seen favoring the diagnosis of chromoblastomycosis. Fungal culture was not feasible.
The patient was then put on oral fluconazole 200mg twice a day and cycles of injection amikacin 750mg/day with three weeks on and two weeks off dosing pattern for three months along with cryotherapy, to which he responded well and the lesions healed with mild scarring over a period of one month [Figures 1b, 2b]. The scrotal swelling did not resolve much. He was then advised surgery for reduction of secondary lymphedema induced genital elephantiasis. | genital elephantiasis, biopsy, chromoblastomycosis | Not supported with pagination yet | null |
PMC7560383_01 | Male | 57 | A 57-year-old male patient was admitted to our unit of General Surgery with a recent diagnosis of ulcerated gastric angulus adenocarcinoma. In anamnesis he reported a history of emphysematous chronic obstructive pulmonary disease (COPD), previous appendectomy and laparoscopic suture repair of perforated gastric ulcer.
The patient reported a weight loss of about 15 kg in the last 12 months associated with abdominal discomfort, heartburn and repeated vomiting episodes. A gastroscopy was performed and a 25 mm ulcerated lesion with irregular edges was revealed at the gastric angulus towards the antrum. Biopsy confirmed a high grade dysplasia associated to adenocarcinoma. No metastatic disease was detected at the staging chest-abdomen CT scan and no clear imaging compatible with parasite bowel infection was detected. The physical examination revealed a state of under-nutrition and tender abdomen; laboratory values were normal. To complete the pre-operative phase, a pharyngeal swab for testing SARS-CoV-2-PCR was performed and a negative result was obtained. After multidisciplinary discussion and preoperative evaluation, the patient was operated from a skilled surgeon on full robotic subtotal gastrectomy with double loop Roux-en-Y reconstruction with standard D2 lymphadenectomy (according to JGCA 2011 gastric cancer classification, 2017 NCCN gastric cancer guidelines) with the application of the da Vinci Si system (Intuitive Surgical Inc, Sunyvale, CA, USA). No intraoperative complications were registered and blood loss were minimal; two abdominal drains were placed and nasogastric tube was removed before awakening. In the immediate post-operative time, about 10 h from the end of surgical intervention, the patient presented with vomiting and siero-ematic material with a single, 5 m-long, yellowish-white colored, elastic, motile tenia and one knot were observed (Fig. 1). At the parassitological analysis it resulted in Taenia Saginata; a strobilus with a high number of proglottids and eggs were identified and no scolex was clearly detected. After consultation with infectious disease team, as soon as the oral intake restarted in fourth postoperative day (POD), a 3 days-therapy with single oral dose albendazol (400 mg) therapy was achieved and a progressive disappearance of eggs in the stools was registered till negative parasitological stools research was obtained. After a new medical interview the patient reported occasional episode of evacuation of filamentous stools and he assumed that he usually did not eat uncooked meat even if he couldn't be sure that it was never happened.
During the postoperative hospital stay, in fourth POD, a water-soluble-contrast upper gastrointestinal X-ray imaging was performed and gastrointestinal outflow resulted regular in absence of anastomotic leakage.
In sixth POD the patient presented with fever and blood exams revealed an increase in C reactive-protein rate (28 mg/dl) with normal white blood cells count. To exclude Covid-related pneumonia, second pharyngeal swab for testing SARS-CoV-2-PCR was repeated, resulted negative; a chest-abdomen CT scan was performed and posterior basal bilateral segments pneumonia without abdominal abnormalities was described. An intravenous broad spectrum empiric antibiotic therapy was added leading to clinical improvements; a high caloric fractionated diet was optimizated and the patient was than discharged in 13th POD.
The histological examination of the tumor revealed a poorly differentiated both intestinal and signet ring cell carcinoma, 57 lymphnodes were harvested and none metastasis were found (pT1b; pN0; pMx; pR0 according to AJCC 8th edition). | case report, parasitic infection, robotic subtotal gastrectomy, taenia saginata | Not supported with pagination yet | null |
PMC4281386_01 | Female | 18 | Armed with patient genetic information, clinicians can more quickly identify effective therapies, thus limiting the prolonged suffering and economic burden placed upon many patients with chronic illnesses. Several examples are available which demonstrate the utility and effectiveness of testing in practice for a variety of clinical diagnoses. This is demonstrated in the following published patient cases. One case describes an 18-year-old male diagnosed with intermittent explosive disorder, suffering from uncontrolled anger outbursts and several failed medication trials, who elected to utilize genetic testing. The results guided his clinician to initiate lithium, which markedly reduced his symptoms, with no adverse medication effects, and allowed him to improve his school work, social, and family life. Lithium was chosen as an intervention for this patient as he had variations in the SLC6A4, DRD2, and 5HT2C, increasing his risk for failure and intolerance with SSRIs and antipsychotic agents. Thus, a treatment strategy which did not target the serotonin transporter or dopamine receptor pathway would likely be better tolerated in this patient. In another patient case, a clinician treating a 31-year-old female suffering from severe depressive symptoms was able to utilize genetic testing, and the resulting therapeutic choices led to complete remission of the patient's symptoms. In this example, lamotrigine was chosen in response to clinical presentation, as well as a variation in the ANK3 gene. ANK3 is a protein related to sodium channels and is involved in neuronal excitability. Lamotrigine was utilized to stabilize the patient's mood and for its potential as a modulator of sodium channel activity. | null | Not supported with pagination yet | null |
PMC9467293_01 | Male | 57 | A 57-year-old man was referred to our hospital with complaints of multiple dark red nodules on the scalp for five years. Five years ago, a soy-sized nodule appeared on the scalp without any discomfort and gradually increased in number and size. The patient was sent to the local hospital seven months ago because of blood in the sputum. The biopsy of the lymph nodes behind the left ear showed that it was in line with Castleman disease, plasma cell type (IgG4>50/HPF, IgG4/IgG>40%). Computed tomography (CT) revealed multiple lymphadenopathies, including the right heart-phrenic angle, retroperitoneum, bilateral iliac area, and groin. Bone marrow biopsy was normal. He was diagnosed with Castleman disease (multicentric plasma cell type). Physical examination revealed multiple irregular-shaped, dark-red, soft to fluctuant, well-demarcated plaques on the scalp ranging from 1 to 8 cm in diameter (Figure 1).
Laboratory tests showed a decreased hemoglobin (Hb, 89 g/L; reference range [RR], 115-150 g/L), elevated erythrocyte sedimentation rate (ESR, 111 mm/h; RR, <20 mm/h), increased C-reactive protein (CRP, 70.4 mg/L; RR, 0-8 mg/L) and positive rheumatoid factor (RF, 21.2IU/mL; RR, 0-15 IU/mL). Serum IgG and IgA levels were high (respectively 62.6 g/L; RR, 7.2-16.8 g/L, 8.90 g/L; RR, 0.82-4.53 g/L), whereas IgM level was normal (1.68 g/L; RR, 0.46-3.04 g/L). Protein immunofixation of serum and urine were negative for M-protein. The serum total protein level was increased (99.9g/L; RR, 60-80 g/L), while the albumin decreased (24.2 g/L; RR, 34-48 g/L), and the albumin-globulin ratio was 0.82 (RR, 1-2). Serum levels of IgG4 (943.0mg/dl; RR, 3-201 mg/dl) were also increased. Serum levels of kappa (49.3g/L g/L; RR, 1.7-3.7 g/L) and lambda (23.4g/L; RR, 0.9-2.10g/L) light chain and urine levels of kappa (34.90mg/dL; RR, 1.7-3.7 g/L) and lambda (12.10mg/dL; RR, 0.9-2.10g/L) light chain was all significantly increased. Serum levels of VEGF (264.21pg/mL; RR, 0-142pg/mL) and interleukin-6 (IL-6, 50.23pg/mL; RR<5.9pg/mL) were all markedly increased. Serologic tests for hepatitis virus types B and C, HHV-8, CMV, EBV, ADV, tuberculosis, syphilis, and HIV antibody were all negative. The biopsy of the lymph nodes behind the left ear showed that small lymphocytes of the mantle zones are arranged in concentric rings around the atrophied germinal center, and amounts of plasma cells in the interfollicular region. The immunohistochemistry results are as followed: CD3 (partial +), CD20 (partial +), Ki67 (+), CD38 (+), CD138 (+), Kappa (+), Lambda (+), BCL-2 (perifollicular +), CD21 (dendritic cell+), CD34 (vascular+), IgG (+), IgG4 (+) (Figure 2). The skin biopsy taken from the right ear revealed variable-sized lymphoid follicles, infiltrated neutrophils, and many plasma cells in the dermis. A broad immunohistochemical panel of CD3, CD20, CD38, CD138, IgG, IgG4, CD34, Kappa, Lambda, BCL-2, and Ki-67 was performed (Figure 3). Based on the clinical, laboratory, and pathological findings, the patient was diagnosed with the plasmacytic variant of idiopathic multicentric CD (pMCD). The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, and the cutaneous lesions disappeared after two months. | castleman disease, plasma cell variant, skin | Not supported with pagination yet | null |
PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Contrast-enhanced chest computed tomography, soft tissue window. (a-d) Demonstrates ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Contrast-enhanced chest computed tomography, soft tissue window. (a-d) Demonstrates ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Contrast-enhanced chest computed tomography, soft tissue window. (a-d) Demonstrates ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Contrast-enhanced chest computed tomography, soft tissue window. (a-d) Demonstrates ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Noncontrast enhanced computed tomography chest, soft tissue window, from 3-years prior. (a-d) Demonstrating ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Noncontrast enhanced computed tomography chest, soft tissue window, from 3-years prior. (a-d) Demonstrating ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Noncontrast enhanced computed tomography chest, soft tissue window, from 3-years prior. (a-d) Demonstrating ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5007905_01 | Male | 71 | A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and TB status posttreatment in 1985, presented for evaluation of chronic, progressive dyspnea. The patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous COPD exacerbations. He had been treated with bronchodilators, corticosteroids, and occasional antibiotics without improvement. He had no history of tobacco use, significant alcohol consumption, or any illicit drug use.
On examination, the patient was in no significant distress and was able to speak in full sentences. His vital signs were normal except for a respiratory rate of 20 breaths/min and oxygen saturation of 90% on room air at rest. Cardiovascular examination was notable for jugular venous distension to the angle of the mandible. A parasternal heave, an accentuated P2, and an S3 were appreciated. Lung auscultation was notable for decreased breath sounds. The remainder of the examination was unremarkable.
Transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmHg. Pulmonary function testing (PFT) demonstrated severe obstructive ventilatory defect with diffusion impairment.
Chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring, pleural thickening and volume loss [Figure 1]. Contrast-enhanced chest CT revealed ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications, enlargement of the main and right pulmonary artery, and irregular narrowing of the right mainstem and upper lobe bronchi [Figure 2]. Positron emission tomography (PET) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions, right more prominent than left. Of note, the patient had undergone a non contrast-enhanced thoracic CT three years prior, which documented relative stability all the abnormal findings, including the bronchial narrowing and pulmonary artery dilation [Figure 3].
The patient had previously undergone a bronchoscopy with bronchoalveolar lavage, brushings, and biopsies which were negative for fungal organisms and acid-fast bacilli.
The patient's known history of TB and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates. Although the PET scan showed mild uptake in the perihilar regions consistent with an active inflammatory process, the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy. The patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography. He also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry. The patient's respiratory symptoms stabilized on supportive medications, and no further interventions were required. | fibrosing mediastinitis, histoplasmosis, mediastinal fibrosis, sclerosing mediastinitis, tuberculosis | A 71-year-old man with a history of chronic obstructive pulmonary disease, pulmonary hypertension, and prior pulmonary tuberculosis infection presenting with progressive dyspnea, diagnosed with tuberculosis-associated fibrosing mediastinitis. Noncontrast enhanced computed tomography chest, soft tissue window, from 3-years prior. (a-d) Demonstrating ill-defined, infiltrative bilateral hilar soft tissue densities with calcifications (white arrows); enlargement of the main and right pulmonary artery (black arrow heads); and irregular narrowing of the right mainstem and upper lobe bronchi (black arrow). |
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PMC5578524_01 | Male | 25 | The patients, 25 years old man, normotensive, non-diabetic, from middle class socioeconomic background presented with abdominal pain, abdominal distention and fever for 1 month. He had no history of joint pain, hematemesis and/or melena, cough or breathlessness, chest pain or palpitation, facial puffiness and urinary complains. He never experienced jaundice and his bowel habit was normal. On clinical examination, the patient was ill looking, anemic, icteric, well oriented and cooperative with average built and nutrition. He had no bony tenderness, lymphadenopathy and any organomegaly. He had ascites and sluggish of bowel sound but liver dullness was not obliterated. He had no edema, flapping tremor and stigmata of chronic liver disease. Others systemic examination revealed no abnormality. Finally, the patient was admitted to a tertiary care hospital for proper evaluation.
Hematological investigations revealed hemoglobin 8.6 gm/dl, ESR-40 mm/lst hour, platelets 890 x 109/l, and total count of WBC 41,100/mm3. Peripheral blood film showed microcytic hypochromic anemia and neutrophilic leukocytosis with thrombocytosis. He tested negative for HBsAg, anti-HCV, anti-HEV Ig M, and anti-HAV Ig M. His bilirubin level was 5.8 mg/dl, serum ALT 24 U/L, serum AST 44 U/L, serum alkaline phosphatase 75 IU/L, LDH 259 U/L and serum albumin 3.3 gm/l. He had normal prothrombin time and D-dimer level. His random blood sugar was 5.6 mmol/l, serum creatinine 0.8 mg/dl and uric acid level 6 mg/dl. He also tested negative for ANA, ASMA, RK39 and malarial parasite. He had CEA 1.97 ng/ml.
Ultrasonography and computed tomography (CT) scan of whole abdomen revealed hepatosplenomegaly and moderate ascites. Endoscopy, colonoscopy and chest X-ray revealed normal findings. A tuberculin skin test was negative and sputum were negative for AFB in three occasions. Ascitic fluid was taped and studied. Ascitic fluid showed lymphocytes 95%, negative for AFB, gram stain and malignant cell. His ascitic fluid protein 38 gm/l, sugar 6 mmol/l and ADA 22.6 U/l. Bone marrow examination was also done. It demonstrated panmyelosis. He had normal Hb electrophoresis study.
In spite of all investigations, definitive diagnosis could not be made. He was identified as a tuberculosis (TB) suspect and was started on treatment with anti-TB drug (CAT-1) and patient gradually felt better. He was subsequently discharge home to directly observed therapy (DOT). His fever improved over the initial weeks of therapy, ascites resolved and engaged himself with his normal daily activities. Two months later, repeat scans and laboratory tests are to be in normal range. | abdominal tuberculosis, diagnosis, tuberculosis | Not supported with pagination yet | null |
PMC9989416_01 | Male | 68 | A 68-year-old Japanese male patient was previously referred to a hospital in November 2012 for further investigation of bilateral hilar lymphadenopathy detected on a chest radiograph, which had been brought to notice at every annual medical checkup for the past 10 years but had not been examined further. The patient had no health complaints or particular medical history. He had worked in sales and had a 15 pack-year smoking history. Chest radiography revealed bilateral hilar lymphadenopathy and reticular shadows in the lower lung fields (Figure 1(a)). CT of the chest showed bilateral hilar and mediastinal lymphadenopathy (Figure 1(b)), and ground-glass opacities and reticular shadows distributed predominantly in both lower lobes (Figure 1(c)).
The vital signs were as follows: body temperature, 36.3 C; blood pressure, 142/72 mmHg; pulse, regular at 72 beats/min; oxygen saturation, 97% (ambient air). Physical examination revealed no abnormalities except for fine crackles in the bilateral lower lung fields. An ophthalmic examination showed no findings of granulomatous uveitis.
Laboratory investigations showed that the C-reactive protein (CRP) level was 0.09 mg/dL (normal < 0.3 mg/dL). Increased levels of lactate dehydrogenase (LDH) (233 U/L, normal < 211 U/L) and Krebs von den Lungen-6 (KL-6) (1121 U/mL, normal < 500 U/mL) were observed. Serological tests showed an anti-cyclic citrullinated peptide (CCP) antibody level of <1.2 U/mL (normal < 4.5 U/mL) and rheumatoid factor (RF) of <1.0 IU/mL (normal < 10.0 IU/mL). The patient's serum angiotensin-converting enzyme (ACE) level was 24.6 U/L (normal < 25.0 U/L).
Pulmonary function test (PFT) revealed mild reduction in FVC, 2.96 L (87.3% predicted), forced expiratory volume in 1 s (FEV1.0), 2.38 L (91.9% predicted), and diffusion capacity of the lung for carbon monoxide (DLCO), 14.03 mL/min/mmHg (83.4% predicted). Although electrocardiography showed complete right bundle branch block, the transthoracic echocardiogram revealed no abnormality.
Bronchoscopy revealed no macroscopic abnormalities. Bronchoalveolar lavage fluid (BALF) analysis showed a cell count of 2.43 x 105/mL, with a cell differentiation of 39.0% macrophages, 61.0% lymphocytes, and a CD4/CD8 ratio of 1.9. Histopathological examination of the transbronchial lung biopsy (TBLB) specimens (right B3b, right B8a) revealed noncaseating epithelioid granulomas in the perivascular connective tissue with lymphocyte infiltration, which was consistent with sarcoidosis (Figure 2(a) and (b)). Alcian blue-positive intraluminal fibrosis with mural incorporation was also observed (Figure 2(c)). No microorganisms, including Mycobacterium spp. and Propionibacterium acnes, were detected in BALF, tissue smears, or lung specimen cultures.
In May 2016, the patient was referred to our hospital. Due to a progressive decline in FVC (>200 mL/year) accompanied by a deterioration of the radiological findings, 25 mg/day oral prednisolone (PSL) was initiated in November 2017 followed by gradual tapering (Figure 3). In March 2020, when PSL was reduced to 12 mg/day, the patient noticed arthralgia and swelling in the right wrist followed by the right third PIP and the left wrist, but not in ankle joints. No skin lesions were found. Although a giant cell tumor of the tendon sheath was tentatively suspected, histopathological examination of the joint lesion showed proliferative synovial tissues with massive infiltration of mononuclear cells, but not granuloma formation or giant cell tumor. Mgnetic resonance imagine (MRI) revealed bone marrow edema in the carpal bones and synovitis in the right wrist. In addition to these findings, a high anti-CCP antibody titer (>500 U/mL) led to the diagnosis of RA in August 2020, though the clinical joint findings were not necessarily typical. Salazosulfapyridine was initiated for the joint lesions.
Gradual progression of dyspnea had been accompanied by a total of 900 mL reduction in FVC during the 4 years until August 2020 (Figure 3). Concordantly, honeycomb changes gradually developed on a series of CT scans over 5 years (Figure 4). Nintedanib was initiated for PF-ILD in January 2021, resulting in a slowing of the FVC decline without the incidence of adverse events such as diarrhea or liver injury. Although home oxygen therapy was introduced in May 2021, FVC was maintained in follow-up pulmonary function tests with successful tapering of PSL to 10 mg/day (Figure 3). As of August 2021, the patient had stable symptoms and chest CT findings and was on regular monthly follow-up. | nintedanib, progressive fibrosing interstitial lung disease (pf-ild), rheumatoid arthritis, sarcoidosis | Not supported with pagination yet | null |
PMC5645168_01 | Male | 17 | A 17-year-old man, living in a metropolis in the south of the country, with no medical history, was admitted to the emergency ward with complaints of a chronic headache evolving for 9 months with some episodes of vomiting and intermittent fever. There had no visual deficit or limb weakness or balance impairment. He received empiric antibiotic in fever episodes without real improvement. On examination, the patient was conscious, febrile (39 C) with stiff neck without limb deficit but some brisk reflexes on the lower limbs. Fundus examination was normal. Cerebrospinal fluid (CSF) was at high pressure and showed 90 cells (neutrophils 56%, lymphocytes 44%), proteins 4,11 g/l, glucose 3.06 mg/dl (blood glucose: 108.1 mg/dl).
Gram stain was normal. Soluble antigens screen using Wellcozyme Oxoid eliminated other pathogens of meningitis. CSF GeneXpert investigation was negative excluding mycobacterium tuberculosis complex.
CSF culture in blood medium grew brucella melitensis while blood culture (BACTEC 960 BC system, Becton-Dickinson) remained negative after 3 weeks of incubation.
Blood formula showed haemoglobin of 10 g/dl with normal WBC and platelets, sedimentation rate, electrolytes, kidney and liver testing. CRP was mildly positive at 13.1 mg/l
Rose Bengal test (Brucellosis slide BioMerieux France) was positive in the serum and CSF. CSF Wright test (brucella wright biorad , France) was positive with a titer of 640. Other serological tests for syphilis, human immunodeficiency virus (HIV), hepatitis B and C virus and Borrelia were negative.
Magnetic resonance imaging (MRI) showed evocative signs of a leptomeningitis with meninges thickening especially in posterior cerebral fossa and spinal cone.
Thoraco-abdominal computed tomography (CT-Scan) showed lymph nodes in the stomachic coronary chains and the coeco-colo-appendicular regions, and discrete anterior vertebral collapse of the D11 without instability signs.
Electroencephalography showed slow spikes in the left temporal lobe. Ophthalmological examination was normal.
We concluded to neurobrucellosis diagnosis. The patient was given rifampicin 900 mg/d, doxycycline 200 mg/d for 3months. Clinical and biological outcome was favourable. | brucellosis, meningitis, neurobrucellosis | Not supported with pagination yet | null |
PMC6313995_01 | Male | 47 | A 47-year-old male patient noticed a change in his voice (hoarseness) 4 months previously. During the anamnesis, he did not report any addictions or habits, but systemic hypertension had been diagnosed and controlled. During intraoral physical examination, a pediculated exophytic lesion with a rough surface and coloration similar to adjacent mucosa was observed in the right tonsil. Examination by laryngoscopy revealed an exophytic lesion in the right paralyzed vocal fold, occupying its anterior two-thirds, in which the mucosa was covered by fibrinopurulent exudate. An incisional biopsy was performed on the vocal cord and excisional on the palatine tonsil. Microscopically, the vocal cord biopsy revealed a squamous epithelium exhibiting architectural disorganization, covered by a fibrinopurulent membrane. This epithelium exhibited projections towards the connective tissue and was infiltrated into the connective tissue, forming islands and strands of malignant epithelial cells (Figure 1).
The squamous layer showed clear epithelial cells with a vacuolized nuclei, and some cells similar to koilocytes were present in the upper layers of the epithelium. The epithelium was found with digitiform projections and fibrovascular connective tissue centers containing mononuclear inflammatory infiltrate (Figure 1(a)). A transitional zone was found in this biopsy, where the atypical epithelium protrudes exophytically with a digitiform aspect (Figure 1(b)). The malignant component showed atypical cells, with nuclear pleomorphism, sometimes binucleated cells, with a hyperchromatic nucleus and individual keratinization. Atypical mitoses and areas of necrosis were also found (Figure 1(c)). The result of the incisional biopsy was of a well-differentiated squamous cell carcinoma (SCC) present in the right vocal cord. Histological examination suggested that the SCC originated from a papillomatous lesion, and chromogenic in situ hybridization (CISH) was performed. Both lesions showed a positive result in CISH for high-risk HPV types 16 and 18 (Figures 1(d) and 1(e)) and negative for low-risk HPV types 6 and 11.
On the other hand, the histological sections of the right palatine tonsil region revealed a squamous papilloma demonstrated by proliferation of the stratified squamous epithelium, predominantly nonkeratinized, presenting exocytosis and basal layer hyperplasia with typical mitoses.
The following procedures were carried out from the biopsy block: dewaxing, peroxidase blockade, and enzymatic digestion, followed by a pretreatment with a 95% EDTA bath for 15 min, followed by several rinses with distilled water and dehydration. After drying, the probe was added onto the material, the slices were covered by a coverslip, and sealing was performed. The material was denatured for 5 min at 75 C, and hybridization was performed at 37 C for 60 min for high-risk HPV. The ZytoFast Plus CISH Implementation Kit-HRP-DAB (ZytoVision, Bremerhaven, Germany, and the ZytoFast HPV-type 6/11 Probe and 16/18 Probe) was used. In the next step, the coverslip was removed, and the slides were washed in TBS buffer at 55 C for 5 min, and then, the primary antibody was incubated at 37 C for 30 min in a humid chamber. For tagging, chromogen diaminobenzidine (DakoCytomation, Carpinteria, CA, USA) was used for 10 min, and Mayer's Hematoxylin was used for the counterstaining. Reactions were performed with negative and positive controls.
Surgery was performed, including tracheostomy, with the final diagnosis of SCC originating from LP, staging T3N0M0. One month after the surgical procedure, the patient returned without complaints. In the other nasofibroscopy and bronchoscopy examinations, no changes were observed. Follow-up by a speech therapist was fundamental for significant voice improvement. The patient has been undergoing maintenance for 36 months and has no complaints and no signs of relapse.
Fifteen articles were found, totaling 27 cases of malignant transformation of LP with onset in adult patients. The mean age of the patients was 57.03 years (SD = 13.76). Of these, including the present case, 25 (89.28%) were male patients (Table 1), and in 3 (10.71%) cases, there was no history of recurrent LP. The localization of the carcinoma was cited in 10 cases, of which 3 (30%) were malignant lesions in the lung, due to dissemination. In the remaining 7 (70%), the larynx was affected, mainly in the vocal cords. There were 9 (47.36%) smokers, and HPV was identified in 9 of the reports, 2 negative tests, 4 with low-risk HPV and 4 with high-risk HPV. | null | Not supported with pagination yet | null |
PMC8749151_01 | Male | 52 | A 52-year-old abbatoir employee from northern New South Wales, Australia, injured his right thigh while attempting to stop bovine intestines falling with his foot in November 2011. He had sudden onset of pain in the adductor insertion, radiating down the medial thigh. Over the next week, pain developed in the buttock and lateral thigh to the knee. Pain and swelling continued over the next few months.
Ultrasound 10 days post-injury demonstrated a tear of the adductor magnus, and plain X-ray was normal. Magnetic resonance imaging 2 months later showed extensive marrow oedema in the femoral head and neck, acetabulum and adjacent hemi-pelvis, with partial collapse of the femoral head, oedema of the gluteal and adductor muscles, and a tear in obturator externus. There was hip synovitis and fluid. C-reactive protein was 98.9 mg l-1.
Subsequent X-rays demonstrated a progressive, destructive process in the femur and acetabulum. Bone scan demonstrated avid focal tracer uptake in the right femoral head and neck. Thirteen months post-injury, the Q fever phase I IgG and total antibody titre was >3200 by immunofluorescence (normal <25), consistent with chronic Q fever. At age 40 at pre-immunization screening, the patient's Q fever skin test had been positive, with an induration diameter of 15 mm, while the Q fever IgG enzyme immunoassay index was 1.4 (<1.0) and the phase 2 complement fixation titre was 2.5 (8-32). After that time, he had not taken antibiotics that are active against Q fever.
Seventeen months post-injury, he attended the Infectious Diseases service. The hip was mildly tender, in fixed flexion, with severely limited passive movements, and active movements limited by pain, with non-pitting oedema of the leg. There was quadriceps wasting with no muscle tenderness. He commenced doxycycline and hydroxychloroquine. Histopathology from synovial core biopsy demonstrated non-granulomatous chronic inflammation. Bacterial, fungal, mycobacterial and C. burnetii culture and PCR were negative after two doses of doxycycline. Cell culture and PCR were processed at the Australian Rickettsial Reference Laboratory (Geelong, Australia). QuantiFERON-TB Gold and brucellosis serology were negative. Echocardiography was normal.
Pain and mobility were much improved 7 weeks later, at 19 months post-injury. The fixed flexion deformity resolved, with nearly normal range of hip motion. C-reactive protein levels had returned to normal and phase I Q fever antibody titres were much reduced (Fig. 1).
The patient underwent a successful two-stage total hip arthroplasty in February 2014 at 27 months post-injury, taking doxycycline throughout. Standard and C. burnetii joint tissue culture and PCR were negative.
The patient received 36 months of doxycycline and hydroxychloroquine, with no relapse in symptoms or radiological change 18 months post-treatment cessation, despite transient elevations in Q fever antibody titres during treatment. | coxiella burnetii, q fever, osteoarticular infection, reactivation | Not supported with pagination yet | null |
PMC6011111_01 | Male | 32 | A 32-year-old Caucasian male with a known history of depression presented to the emergency department accompanied by police after a violent outburst following prolonged DFE abuse during a suicide attempt. On admission, he was emotionally labile and had contusions on his left shoulder and upper extremities due to a physical altercation with police. He was initially confused and verbally abusive, but within six hours he was oriented, cooperative, and able to provide a reliable history.
The patient stated that he had huffed keyboard cleaner several days per week for the past year; however, the frequency had increased over the last month to several times daily. Other than depression, the patient had no other known medical problems. He denied any personal or family history of kidney disease. The patient denied drinking alcohol, and he reported smoking one-half pack of cigarettes per day for the previous two years. He denied any other substance abuse except for DFE. He reported no use of nonsteroidal anti-inflammatory (NSAID) medications. During this episode of difluoroethane abuse, he had no loss of consciousness, but experienced frightening visual and auditory hallucinations as well as anxiety that persisted even after returning to his self-reported baseline mental status.
Initial labs revealed a WBC count of 21,000 with polymorphonuclear predominance of 81%, an elevated creatinine of 1.5mg/dL with no known baseline, BUN of 10mg/dL, GFR of 54 mL/min/1.73 m2, lactic acidosis, creatine kinase of 350 U/L, and a carboxyhemoglobin level of 3.1%. Urinalysis was significant for 3+ proteinuria, moderate blood, 14 RBCs, 3 WBCs, and 3 hyaline casts. He had a negative urine drug screen.
The patient received single renally adjusted doses of Vancomycin and Piperacillin-Tazobactam, intravenous 0.9% saline, and oxygen by nasal cannula while in the emergency department prior to admission. Over the next 24 hours, he received intravenous fluids and oxygen with subsequent normalization of lactic acid, creatine kinase, and leukocyte count. His creatinine down trended to 1.3mg/dL. However, 36 hours into admission, his serum creatinine inexplicably rose to 2.3 with a rise in carboxyhemoglobin to 3.6%, while his urine output remained stable (Figure 1). Repeat urinalysis showed a small amount of blood with RBC of 2, negative proteinuria, and no evidence of infection.
His normal saline infusion was transitioned to bicarbonate with saline, but was discontinued after the patient developed pruritus. Ultimately, he was transitioned to normal saline at 75 ml/hour. A renal ultrasound showed increased echogenicity of both kidneys consistent with medical renal disease, without change in size, atrophy, or cystic lesions (Figure 2). Thus, it is likely that the patient had some degree of chronic kidney disease (CKD) prior to admission. For the next three days, he continued to receive intravenous normal saline with subsequent improvement of creatinine and normalization of his urinalysis and was discharged with a creatinine of 1.6. | null | Not supported with pagination yet | null |
PMC5671702_01 | Female | 71 | A 71-year-old woman from Dominican Republic was admitted for dyspnea, fever, and nonproductive cough of one-day duration. Her medical history was significant for diabetes mellitus, systolic heart failure, gastric B-cell lymphoma treated with chemotherapy, and surgically treated basal cell carcinoma of forehead. She was a heavy smoker with 40 packs/year. She denied alcohol or illicit drug use. Family history was noncontributory. There were no sick contacts, recent traveling, or occupational exposures and no history of exposure to tuberculosis.
Initial examination showed an elderly woman on respiratory distress. Chest auscultation revealed bibasilar crackles and diffuse expiratory wheezing. There were no palpable lymphadenopathy, organomegaly, or skin lesions. The rest of exam was unremarkable. Significant laboratory findings included elevated Pro-BNP; there was no leukocytosis and renal and liver function was normal. A right sided thoracentesis was performed with pleural fluid analysis revealing transudative effusion with pleural/serum LDH ratio of 0.12 and pleural/serum protein ratio of 0.19.
Patient was treated for exacerbation of heart failure with diuretics and antibiotics were given for presumptive community acquired pneumonia with clinical improvement.
Chest-roentgenogram (CXR) on admission showed bilateral pleural effusion and infiltrates which rapidly improved suggesting a diagnosis of heart failure rather than pneumonic process (Figure 1). A chest computed tomography (CT) revealed a 15 mm spiculated nodule in the right upper lobe, a 10 mm nodule in the left upper lobe, chronic interstitial fibrosis, and a right paratracheal lymph node measuring 3.1 cm, unchanged from a prior chest CT performed three months prior (Figure 2).
Patient underwent flexible fiberoptic bronchoscopy (FFB) that revealed a small endobronchial lesion at the right upper lobe before the takeoff of anterior segmental bronchus. Endobronchial biopsy (EB) of the EBL as well as transbronchial biopsy (TBBx) of right upper nodule and EBUS-TBNA of the right paratracheal and subcarinal lymph nodes was performed. A 19'' gauge needle was used for the EBUS-TBNA with a total of four needle passes per lymph node. Twenty ml of purulent appearing fluid was aspirated from the right paratracheal lymph node (Figure 3). Aspirated EBUS fluid showed highly atypical squamous cells in necrotic background. The EB of right upper lobe endobronchial lesion and the core biopsy of material aspirated from 4R lymph node were consistent with squamous cell carcinoma (Figure 4). Cultures of blood, urine, lung tissue, and EBUS-TBNA aspirate were all negative for bacterial infections, fungal infections, and mycobacteria. Serology for mycoplasma and urine for legionella were all negative. Collagen vascular workup was negative as well. The patient received palliative chemotherapy. | null | Not supported with pagination yet | null |
PMC7134815_01 | Female | 36 | A 36-year-old G2P0SA1 woman traveled to China during the SARS outbreak. At the time, she was not aware that she was 7 weeks pregnant and during her stay in China she developed cold and cough symptoms. She was seen by a physician who advised her to receive a total of six injections of 200 mg ribvirin intramuscularly (IM) daily for three days. Eventually she received a total of three injections of 200 mg IM ribavirin within a 3-day period. She did not recall receiving any other medications beside ribavirin. The possibility of SARS in her case was ruled out by further investigation, and her cold symptoms subsided. She continued her pregnancy without any complications and at 13 weeks of pregnancy she called Motherisk in order to get information regarding ribavirin exposure and possible adverse effects on her current pregnancy. She was sent for ultrasound (US) at 11, 18 and 27 weeks of pregnancy and all reported to be within the normal range. Because of her age, she underwent amniocentesis at 18 weeks of pregnancy with negative results. Her pregnancy continued uneventfully. She developed some contractions at 40 (+3) weeks and with the assist of induction she delivered a baby girl with normal Apgar scores. Birth weight was 3.35 kg (7 lb and 6 oz). Her baby did not need any specific medical attention and did very well during the hospital stay. She and her baby were discharged from the hospital at 48 h. Her newborn developed mild jaundice on postnatal day 3 which did not necessitate any treatment and subsided after a few days. According to maternal report, her baby is 8 months old and healthy. She stated that the child has been followed by a pediatrician since birth. She was last seen by her pediatrician at 8 months of age. As reported by the infant's pediatrician, her physical examination was completely normal with no evidence of malformations or minor anomalies. She was able to sit up straight by herself without any support, babble, and have central grasping at 8 months of age. Her pediatrician also confirmed that her neurodevelopmental milestones have been within the normal range. The mother did not express concerns regarding the growth and health of her baby at the time of the follow up interview. | null | Not supported with pagination yet | null |
PMC6424054_01 | Female | 52 | A 52-year-old Caucasian woman was admitted to our surgical department. She complained of difficulty eating solid food, impaired swallowing, persistent nagging pain behind the sternum, periodic heartburn and nausea, sickness. The woman had lost 6 kg in the previous 2 months. She had been using antacid medications without prescription for a month with no effect. The patient denied smoking and alcohol intake. The woman had no previous surgical or another medical history.
The diagnostic measures included esophagogastroduodenoscopy (EGD) with biopsy and contrast chest spiral computed tomography (contrast CT) scan. EGD revealed tumor almost completely obturating the lumen in the middle third of the esophagus (25 cm from incisors), impassable for the endoscope. A biopsy was taken. The histopathological examination showed esophageal squamous cell carcinoma (SCC).
CT scan confirmed the diagnosis, showing 33 x 29 x 55 mm tumor of the middle third of the esophagus intensively and irregularly absorbing contrast (Fig. 1). Above the tumor, the esophagus was dilatated and contained a little amount of fluid. There was one increased paratracheal lymph node in mediastinum with the size of 8 mm. No other pathologic changes were diagnosed. Endoscopic ultrasound (EUS) was not performed because of patient's medical insurance peculiarities. The tracheobronchoscopy showed no invasion of the tumor into the tracheobronchial tree and no other pathological changes. Abdomen CT revealed no distant metastases and no abdominal lymph nodes involvement.
The patient was diagnosed with cancer of middle third of esophagus T3N1M0, stage IIIB. According to national clinical standards the patient underwent surgical treatment. The time from the moment of admission to the hospital until the operative treatment was 3 days.
Operative technique (the operative technique of thoracoscopic stage is described in details in our previous case report):
The patient was initially placed in the supine position, and a double lumen endotracheal tube was placed in preparation for the thoracoscopic mobilization of the esophagus. The abdominal stage was open (laparotomy). The gastric tube was formed by dissecting gastrocolic ligament along the greater curvature from the body of the stomach to the subcardial part preserving the right gastroepiploic artery. Then short gastric vessels, gastrophrenic ligament, abdominal part of the esophagus, hepatogastric ligament were cut. The left gastric artery was cut after lymph node dissection in the area of hepatic and splenic arteries, celiac trunk. The gastric tube was formed from the fundus by resecting small curvature by 2 cassettes of 100 mm linear stapler (Covidien, Ireland), leaving 35 mm gastric pouch. The phrenic vein together with a part of diaphragmatic cruses was cut, expanding the esophageal opening of the diaphragm for gastric conduit and the tumor withdrawal. Then the laparotomy incision was closed and the patient was turned to the prone position for the thoracoscopic mobilization of the esophagus and creation of the intrathoracic anastomosis.
Further four trocars were placed into the right pleural cavity: two 10 mm, one 12 mm and one 5 mm. After the right lung collapse, mediastinal pleura was incised from diaphragm continuing up to 2-4 cm above the carina using EnSeal tissue sealer. The azygos vein was clipped with Hem-o-lock (Weck Closure Systems, Research Triangle Park, NC, USA) and cut.
The esophagus was mobilized with the fat tissue and the lymph nodes around it up to the planes of the aorta, the pericardial sac, and contralateral pleura. Then the esophageal tumor with sizes of 6.5 x 4 cm tightly adjoined to the first main bronchus and trachea became visible. The tumor was hard to dissect in the plain of the trachea and the bronchus. The esophagus was mobilized up to the level of the pleural dome, taken on the holder and separated from the tracheobronchial tree.
Next, the esophagus was cut off using the Endopath Echelon Flex 45 stapler (Ethicon, USA) with a 45 mm yellow cassette at the distance of 5 cm from the tumor. After the specimen was removed two defects of the tracheobronchial tree were detected. The first rupture with sizes of 15 mm was situated in the area of the left main bronchus right below the tracheal bifurcation (Fig. 2). Another defect was located on the membranous part of the trachea and had the size of 30 mm (Fig. 3). The intraoperative ruptures were sewn on an endotracheal tube using continuous Stratafix 3.0 suture (Fig. 4). In the area of tracheal rupture the suture was additionally covered by mediastinal pleura. An underwater air leak test was made for the impermeability of the suture.
Next, the resected part of the esophagus was placed into a plastic container and moved into the abdominal cavity through the esophageal opening of the diaphragm. Then the gastric tube was pulled into the mediastinum and trial comparison of the edges of the anastomosis without tension was performed. The gastric tube was fixed to the remaining part of the esophagus by Vicryl 2.0 suture. After that, the stomach and the esophagus were opened using electrocauter. The esophagogastroanastomosis was performed using V-loc 2.0 suture at the level of the pleural dome (Fig. 5). Then, the nasogastric tube was inserted below the anastomosis for decompression. In the next place, the anastomosis zone was covered with stomach using Vicryl 2.0 sutures with the purpose of antireflux protection.
A methylene blue test of the anastomosis was performed; there was no data for dehiscence and leakage. Then the pleural cavity was drained on the right side by two drain tubes; trocars were removed and trocar wounds were sutured. The resected specimen was removed from the abdominal cavity and sent to the laboratory for pathological examination.
The surgery was performed by the team, consisted of 3 experienced in thoracoscopy surgeons. The overall operative time was 345 min. The patient was extubated 1 h after the end of the operation with no signs of respiratory disorders. There was no air leakage through the pleural drains and they were removed on 5th postoperative day. The woman tolerated the surgery well and started to take in a liquid food on the 6th postoperative day. On the 10th day after the surgery an esophagogram with liquid contrast (Urografin) was performed (Fig. 6).
On the 12th day after the surgery the patient was discharged from the hospital in a good state of health with standard dietary and medical recommendations. There were no postoperative complications, no symptoms of dysphagia, nausea or vomiting. | case report, esophageal cancer, intraoperative complications, thoracoscopic esophageal resection, trachea rupture | Not supported with pagination yet | null |
PMC5676363_01 | Male | 50 | A 50-year-old male sushi chef who had never traveled outside Japan presented with a 2-day history of fever and muscle pain. Laboratory investigation yielded the following results: white blood cells (WBC): 7780/microL; platelets: 89000/microL; C-reactive protein (CRP): 36.4 mg/dL; blood urea nitrogen (BUN): 47 mg/dL; creatinine: 2.41 mg/dL; and total bilirubin (T-Bil): 2.0 mg/dL. The day after he was admitted to the hospital, the patient's condition worsened, as indicated by the laboratory data: WBC: 6700/muL; platelets: 50000/microL; CRP: 32.49 mg/dL; BUN: 66 mg/dL; creatinine: 2.81 mg/dL; and T-Bil: 5.6 mg/dL. He was presumptively diagnosed with bacterial pneumonia, atypical pneumonia, and miliary tuberculosis. He was also diagnosed with leptospirosis on the basis of jaundice, renal failure, and thrombocytopenia. He was administered the broad-spectrum antibiotics ceftriaxone, levofloxacin, and minocycline on the first day of admission to the referral hospital. Vancomycin and meropenem were administered on the second day. He was also given the antitubercular agents:isoniazid, rifampicin, pyrazinamide, and ethambutol:even though the results of a tuberculosis screening test were negative. Despite these treatments, his systolic blood pressure dropped to 70 mmHg, and his respiratory condition deteriorated; he was intubated 5 days after the onset of symptoms, which is three days after admission to the previous hospital. An X-ray showed bilateral alveolar infiltrates, and blood gas analysis revealed the following: pH: 7.390; partial pressure of arterial carbon dioxide (PaCO2): 28.3 mmHg; and partial pressure of arterial oxygen (PaO2): 70.4 mmHg HCO3- 16.8 mmol/L with fraction of inspired oxygen (FIO2) of 1.0 as well as positive end-expiratory pressure (PEEP) of 10 cm H2O. The patient developed a life-threatening condition with septic shock and severe acute respiratory failure, despite optimal medical treatment. He was referred to our center for ECMO. Our ECMO team decided to initiate V-V ECMO at the previous hospital and transport the patient on V-V ECMO because the patient was severely hypoxic and needed maximal doses of norepinephrine, epinephrine, and vasopressin to stabilize his cardiac condition. Cannulation was performed via the right femoral vein with 25-French drainage cannulae (HLS Cannulae Maquet Cardiopulmonary, Hirrlingen, Germany) for access and via the right internal jugular vein with 23-French cannulae for return. The ECMO circuit was an adult ECMO bypass custom tubing pack consisting of a Rotaflow centrifugal pump (Maquet Cardiopulmonary GmbH, Hirrlingen, Germany) and gas exchanger (MERA NHP Excelung NSH-R HPO-23WH-C , Senko Medical Inc., Tokyo, Japan). V-V ECMO was initiated at a blood flow rate of 4.0 L/min, with sweep gas flow through the oxygenator at 4.0 L/min of 100% oxygen. After the procedure, the patient's SpO2 was 94%, heart rate was 131 beats/min, and blood pressure was 142/74 mmHg on 0.1 mug/kg/min of epinephrine and 0.3 mug/kg/min of norepinephrine. He was transported to our center via ground ambulance.
After he was transported to our ICU, we maintained the ECMO blood flow at >3.0 L/min during the first 3 days of ECMO because his activated partial thromboplastin time was maintained at around 40-50 s, which was lower than normal because of bleeding (Table 1). After bleeding was controlled, we decreased the ECMO blood flow gradually to 1.5 L/min when peripheral capillary oxygen saturation (SpO2) was over 90%. During V-V ECMO the mechanical ventilation was set at the lung rest setting, which consisted of a driving pressure of 5 cm of water, PEEP of 12 cm of water, and FIO2 of 0.4. Fiber-optic bronchoscopy showed diffuse endobronchial bleeding. The patient was systemically heparinized to maintain an activated partial thromboplastin time of 40-50 seconds, which was lower than the normal value for V-V ECMO. Dobutamine was initiated at 3 microg/kg/min because transthoracic echocardiography showed that the ejection fraction was 30%, mitral regurgitation was moderate, and tricuspid regurgitation was severe. After initiation of dobutamine, his cardiac function improved, epinephrine was stopped the next day, and norepinephrine was stopped the day after that. He remained oliguric and needed renal replacement therapy for 7 days. At the time of presentation to our center, his WBC count was 18,000/microL, CRP level was 24.52 mg/dL, and procalcitonin level was > 100 ng/mL. Although we thought of a wide variety of infections as differential diagnoses, we strongly suspected leptospirosis on the basis of severe acute respiratory failure, myocardial pericarditis, renal failure, jaundice, and thrombocytopenia, which made us continue the broad-spectrum antibiotics, levofloxacin, vancomycin, meropenem, antitubercular agents, and add benzylpenicillin. Because of pulmonary hemorrhage, he was given a platelet transfusion (20 units) for the first 3 days of V-V ECMO therapy. Even though his pulmonary hemorrhage improved on day 8 of V-V ECMO, computed tomography scans showed bilateral ground-glass opacities, bilateral pleural effusion, and atelectasis. Rehabilitation, including sitting on the edge of the bed and standing, was initiated. On day 6 of ECMO therapy, polymerase chain reaction analysis of urine samples collected at the previous hospital confirmed the presence of leptospiral DNA. The tests for tuberculosis, Legionella urinary antigen, pneumococcal antigen, serum Mycoplasma antibody, and Chlamydia pneumoniae antibody all yielded negative results. We switched the intravenous antibiotics from broad-spectrum antibiotics to benzylpenicillin (12 million units/day).
On day 11 of ECMO therapy, blood tests showed improvements in platelet count and serum CRP, creatinine, and T-Bil levels (Figure 1). In addition, the amount of sputum decreased, and improvements were observed in his chest X-ray (Figure 2), compliance, and oxygenation (Figure 3); therefore, we performed a 2-hour trial off-test. The patient tolerated the trial without O2 flow to the oxygenator; therefore, we decided to wean him off ECMO. He was extubated 2 days after being taken off ECMO and transferred back to the previous hospital 2 days after extubation. His last blood gas analysis revealed the following results: pH: 7.468; PaCO2: 36.6 mmHg; PaO2: 67.2 mmHg; and HCO3-: 26.2 mmol/L on room air. Laboratory investigation revealed the following results: WBC: 7400/microL; platelets: 256000/microL; CRP: 1.13 mg/dL; BUN: 29.1 mg/dL; creatinine: 1.36 mg/dL; and T-Bil: 7.9 mg/dL. Finally, paired serum antibody titer testing (on days 5 and 19 after the onset of symptoms) showed a fourfold or higher increase in antibody titers for Leptospira interrogans serovar Copenhageni and Leptospira interrogans serovar Icterohaemorrhagiae, confirming the diagnosis of leptospirosis. | null | Not supported with pagination yet | null |
PMC10442170_01 | Male | 48 | 48-year-old male with no known comorbidities presented with complaint of abdominal pain, low-grade fever, loss of appetite, and weight since last 1 month. Ultrasound abdomen of this patient was suggestive of multiple abscesses in the left lobe of the liver, the largest measuring 4.5 x 4.8 x 3.6 cm, for which the patient had received various treatments at multiple health centers over the past month including injectable and oral antibiotics.
The patient was subsequently admitted in our hospital and thoroughly evaluated which includes a detailed history, clinical examination, biochemical, pathological, microbiological tests, and radiological imaging (Table 1). The significant laboratory and radiological finding were anemia, low albumin, high CRP, normal chest x-ray (Figure 1), and abdominal ultrasonography suggestive of identical sized abscesses in the left lobe of the liver and computed tomography of the abdomen suggestive of multiple liver abscesses in the left lobe with no other abnormalities, and then the patient underwent ultrasound guided pus aspiration and aspirate sent for fluid analysis.
The fluid cytology showed that fluid was suppurative with primarily degraded, viable polymorphs, acid fast bacilli in a necrotic backdrop. The cartridge-based nucleic acid amplification test (CBNAAT) for MTB of the aspirated sample detected MTB that was rifampicin-sensitive. Patient was then started on antitubercular treatment as per the standard National Tuberculosis Elimination Program guidelines for tuberculosis according to weight (patient's weight-52 kg) which comprises four 1st line drugs for a duration of 6 months (details in Table 2) and discharged with regular follow-up in the medicine outpatient department. During follow-up, he responded well to the treatment. | null | Not supported with pagination yet | null |
PMC7372138_01 | Male | 29 | A 29-year-old man with no known medical illness presented with prolonged fever, cough and pleuritic chest pain for 3 days. On examination, he had reduced breath sounds and stony dullness over the right lung. He was febrile but otherwise had stable vital signs with oxygen saturation of 95% on 3L of oxygen. He had significant positive contact history with a colleague who was diagnosed with smear positive pulmonary tuberculosis.
Initial chest radiograph showed a right lower zone consolidation with pleural effusion (Fig. 1A). Septic parameters were raised and he had acute kidney injury (Table 1). He was started empirically on ceftriaxone 2g daily which was escalated to tazobactam/piperacillin 4.5g thrice daily in view of persistent fever. Intercostal chest catheter (ICC) was inserted which drained only 100 mls of serosanguinous fluid due to the presence of septations (Fig. 1B). Pleural fluid analysis was exudative in nature. Pleural fluid and bronchoalveolar lavage culture were sterile. The elevated pleural fluid adenosine deaminase of 64.8 U/L with pleural fluid lymphocytosis and positive Xpert Mycobacterium tuberculosis/rifampicin assay confirmed the diagnosis of tuberculous pleural effusion; hence fixed-dose combination anti-tuberculosis (anti-TB); akurit-4 was started and antibiotic was withheld.
We decided for intrapleural fibrinolytic therapy (IPFT) and he received 3 doses of alteplase 16 mg and DNase 5 mg in 24 hours. There was an increase in daily drainage from 220 mls to 1100 mls and 340 mls. The patient's cough improved and his fever subsided. Both chest radiograph and thoracic ultrasound imaging showed improvement of the effusion(Fig. 1C and D), and he was discharged well and completed 6 months of anti-TB.
A 76-year-man with underlying diabetes and hypertension was referred for further management of a complex pleural effusion and liver abscess. He gave a two-week history of right-sided pleuritic chest pain and hypochondriac pain, lethargy, loss of appetite and weight. On examination, he was febrile with stable vital signs. Oxygen saturation was 95% on 3 L of oxygen. He had reduced breath sound and stony dullness over the right lung and hepatomegaly with liver span of 14 cm.
The infective blood parameters were raised (Table 1). Chest radiograph revealed right-sided loculated effusion (Fig. 1E). Computed tomography (CT) thorax revealed a multi-loculated right pleural collection with collapse consolidation of apicoposterior segment of the right upper lobe with liver abscess (Fig. 1F). As he had completed 10 days of amikacin 750mg daily and meropenem 1g thrice daily at his previous hospital, he was commenced on tazobactam/piperacillin 4.5g thrice daily in our centre.
ICC was inserted which drained only 100 mls purulent fluid overnight. Pleural fluid analysis revealed exudative effusion with pleural LDH of 8665 IU/L (Table 1). Pleural fluid and liver abscess were drained and culture grew Klebsiella pneumoniae. He was treated as invasive Klebsiella syndrome and antibiotic was de-escalated to amoxicillin/clavulanate group based on sensitivity. Three courses of intrapleural alteplase 16 mg with DNase 5 mg were administered as per our protocol to facilitate pleural drainage. Significant drainage was achieved subsequently which led to improvement of infective blood parameters, and imaging (Fig. 1G and H).
In view of the persistent liver abscess, he completed 28 days of intravenous amoxicillin/clavulanate and 6 weeks of oral amoxicillin/clavulanate. He remained well on follow up. | alteplase, dnase, empyema, pleural infection, short-course | Not supported with pagination yet | null |
PMC7372138_02 | Male | 54 | A 54-year-old man with underlying diabetes, hypertension, and smear negative pulmonary tuberculosis (diagnosed via positive sputum Xpert Mycobacterium tuberculosis/rifampicin assay) on day 56 of intensive phase therapy was referred to our centre for further management of a complex left pleural effusion. Clinically he was tachypnoeic with a respiratory rate of 30/minute, heart rate of 110/minute and febrile at 38 C. Oxygen saturation was 93% on 3L of oxygen.
The infective blood parameters were raised (Table 1). Chest radiograph revealed left moderate pleural effusion (Fig. 1I). CT thorax showed multifocal empyema and lung abscess (Fig. 1J). Blood and pleural culture were negative. He was started on tazobactam/piperacillin which was escalated to meropenem after 72 hours in view of persistent fever and raised infective parameters.
ICC was inserted which drained minimal amount of purulent fluid. Pleural fluid analysis are listed in Table 1.
IPFT was decided; he received 3 doses of alteplase 16 mg and DNase 5 mg as per our protocol. Subsequent drainage increased to 1.1 L. The fever and breathlessness resolved and there was improvement of infective parameters. Chest radiograph (Fig. 1K) showed improvement of the effusion. He was discharged with amoxycillin/clavulanate 625 mg thrice daily for 4 weeks and maintenance therapy of anti-TB. A repeat CT thorax done on follow-up in clinic a month later, showed complete resolution of empyema (Fig. 1L). | alteplase, dnase, empyema, pleural infection, short-course | Not supported with pagination yet | null |
PMC9290109_01 | Female | 88 | An 88-year-old Hispanic woman with diabetes mellitus, hypertension, and reactive airway disease presented to the emergency department with a 3-day history of dyspnea. Associated symptoms included productive cough, subjective fevers, and generalized myalgias. The patient had recently returned from a trip to Mexico where she was exposed to multiple family members infected with SARS-CoV-2.
Vital signs at presentation included temperature 36.9 C, blood pressure 84/50 mmHg, heart rate 109 beats per minute, respiratory rate 25 breaths per minute, and oxygen saturation 97% on ambient air. Upon ambulation, patient experienced hypoxia with oxygen saturation 80% on ambient air. Physical examination was pertinent for positive bronchial breath sounds on the right chest.
Laboratory studies were significant for bandemia of 50%, lactic acid 2.5 mmol/L (reference range 0.4-2.0 mmol/L), procalcitonin 3.6 ng/mL (normal high <= 0.50 ng/mL; critical high > 1.99), and elevated inflammatory marker C-reactive protein (CRP) 4.99 mg/dL (normal high <= 0.30). Nasopharyngeal swab for SARS-CoV-2 RNA was reactive. Swabs from nares for influenza A and B antigens were negative. Chest radiograph revealed a 7-cm right upper lobe (RUL) opacity (Image 1). Subsequent computed tomography (CT) angiogram of the chest revealed a large RUL consolidation with air bronchograms, scattered ground-glass opacities, and mediastinal lymph nodes with no evidence of pulmonary emboli (Image 2(A) and (B)).
She was initiated on ceftriaxone 1 g intravenous (IV) every 24 hours and azithromycin 500 mg IV every 24 hours for suspected community-acquired pneumonia. She was started on prednisone 40 mg oral (po) daily in the setting of hypoxia and COVID-19. Bacterial sputum culture was ordered, however was, unfortunately, not collected for reasons that remain unclear. Coccidioidomycosis serology was negative, including nonreactive immunodiffusion for IgM and IgG as well as complement fixation titer <1:2. QuantiFERON tuberculosis gold test was also negative. In addition, 2 sputum acid-fast bacillus smears and cultures were negative. Preliminary routine blood cultures (aerobic and anaerobic bottles) grew Gram-negative diplococci in 1 of 2 bottles from 1 set and final culture revealed NM (Image 3(A) and (B)). Subsequently, ceftriaxone was increased to 2 g IV every 24 hours.
The patient remained alert and oriented and denied any headaches or neck stiffness. Neck was supple with no nuchal rigidity or signs of meningismus. Therefore, suspicion for meningitis was low and lumbar puncture was not performed. Bronchoscopy was considered, however was deferred given the patient's improvement in symptomatology with antibiotic therapy and in an attempt to reduce potential exposure to coronavirus by avoiding an aerosolizing procedure.
Repeat blood cultures revealed no growth. The patient remained on airborne isolation precautions while in the hospital and infection control was notified of the blood culture growing NM. After 5 days of ceftriaxone therapy, the patient was discharged home with supplemental oxygen at 2 L via nasal cannula for COVID-19-associated hypoxia. Results of susceptibility testing were not available at the time of discharge; however, per the Infectious Disease service recommendations, she was also discharged with 9-day supply of amoxicillin/clavulanic acid 875 mg/125 mg po twice daily to complete a total of 14 days of antibiotic therapy.
The NM sensitivities returned approximately 4 weeks after discharge. The isolate was sensitive to ceftriaxone, chloramphenicol, and meropenem but was resistant to ampicillin, levofloxacin, penicillin, and trimethoprim/sulfamethoxazole (Table 1). Patient was seen in the geriatric clinic approximately 3 months after discharge at which time her symptoms had completely resolved and she was no longer hypoxic. Repeat chest X-ray at 3 months demonstrated near-complete resolution of the previously noted RUL consolidation (Image 4). | neisseria meningitidis, antibiotics, chemoprophylaxis, meningococcal pneumonia, pneumonia | Not supported with pagination yet | null |
PMC5845214_01 | Female | 10 | In this study, A. baumannii strains 554S and 554L were isolated from the blood sample of a 10-year-old girl with a burn injury who was hospitalized at Taleghani Burn Hospital in Ahvaz, southwest Iran, on July 25, 2012. On July 27, she became febrile, so a blood culture was realized. Because of the delay between admission and positive culture, we considered that the infection was hospital-acquired. From July 27 to July 31, she was treated empirically with 20 mg of amikacin and 1 g of ceftazidime. Then, on August 1, her antibiotic treatment was replaced with 500 mg of meropenem and 2 g/250 mg of piperacillin-tazobactam. From August 3 to August 11, this treatment was replaced with 500,000 IU of colistin. Then, the patient moved hospitals and sadly died on August 21, 2012. Thus, we believe that the patient eventually died from the burn injury and not from the infection with these bacteria. After the blood sample was plated on chocolate agar, two different colonies with different morphological aspects were observed: one small and one large colony (Fig. 1). The two isolates were identified by MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; Microflex, Bruker Daltonics, Bremen, Germany) as Acinetobacter baumannii strains. Antibiotic susceptibility testing (AST) was performed by the disc diffusion method and interpreted according to the European Committee on Antimicrobial Susceptibility Testing guidelines (http://www.eucast.org/). The two isolates were resistant to carbapenems but full AST revealed that the strains do not have the same profile. The isolate 554L harboring blaOXA-23 was resistant to all antimicrobials tested with the exception of tigecycline and colistin, whereas the isolate 554S harboring blaOXA-72 was also susceptible to doxycycline and tetracycline (Table 1).
Genomic DNA (gDNA) of A. baumannii strains 554S and 554L were sequenced on a MiSeq sequencer (Illumina Inc., San Diego, CA, USA) using the paired-end strategy. Raw reads were assembled with A5-miseq software. Genomes annotation was performed by Rapid Annotation using Subsystem Technology (RAST). tRNA gene detection was performed using the tRNAScanSE 2.0 tool, whereas ribosomal RNA genes were detected using RNAmmer. The sequence type (ST) of strains was analyzed by the MLST 1.8 server of the Center for Genetic Epidemiology. Antimicrobial resistance gene profiling was performed in silico using ARG-ANNOT. Further bioinformatic analysis, such as identification of genomic islands, prophage sequences, clustered regularly interspaced short palindromic repeat (CRISPR) sequences, secondary metabolite gene clusters and plasmid presence were predicted by employing IslandViewer, PHASTER, CRISPRFinder, antiSMASH and Plasmid finder tools, respectively. The percentage of similarity between strains was calculated by pairwise comparison of their Average Nucleotide Identity based on Blast (ANIb) by Jspecies software.
The draft genome of 554S had 386 scaffolds that comprised 4,056,106 bp with a 39% G + C content. Similarly, the 554L draft genome was composed of 580 scaffolds, having a total size of 3,922,359 bp long with 39.1% G + C content. The draft genomes of A. baumannii strains 554S and 554L contained 3884/3689 coding sequences, 8/8 rRNAs, 64/62 tRNAs, respectively. In silico MLST analysis using the Pasteur Institute typing scheme revealed that strains 554S and 554L belong to ST 307 and ST 2, respectively. The strain 554S had 97.1% of similarity with the strain 554L. ARG-ANNOT result analysis revealed that the genomes of strains 554S and 554L encoded 12 and 16 antimicrobial resistance genes, respectively. Genes that harbored resistance to beta-lactams (blaMBL, blaA1, blaA2), aminoglycosides (armA, aphA6), macrolides (mphE, msrE) and sulfamides (sul2) were detected in both genomes. Moreover, in the 554S genome we found genes blaADC-76, blaOXA-72, blaOXA-235, blaOXA-64, while the genes blaADC-73, blaTEM-1D, blaOXA-23, blaOXA-66, aph3"Ia, strA, strB and tetB were unique to the 554L genome (Table 1). Both strains presented the disrupted ATPase encoding comM gene. The genome of the isolate 554S contained at least 28 genomics islands and one complete prophage sequence. Also, three CRISPR sequences could be predicted. For the genome of the isolate 554L, 23 genomic islands and one incomplete prophage sequence were found but no CRISPR sequences. The presence of three putative secondary metabolite gene clusters, including arylpolyene, siderophore and non-ribosomal peptide synthetase (NRPS) gene clusters, could also be predicted in both genomes whereas hserlactone-arylpolyene was predicted only in the 554L genome. Neither strain carried a plasmid. | acinetobacter baumannii, carbapenemase, genome, iran | Not supported with pagination yet | null |
PMC7468399_03 | Female | 62 | A 62-year-old female patient (Table 1, Patient 28) presented to our office on 6 June 2019 with a history of dizziness. She reported being struck in the head by a football in September 2017. There was no history of loss of consciousness, but she was seen in the emergency room and was diagnosed with concussion. Soon after the event, she began developing progressively increasing dizziness. She described a sensation of being pushed and had a feeling that she would fall when exposed to something as trivial as a wind gust. During all waking hours she described a feeling of being in a "funhouse," and was extremely unstable on her feet. She was unable to go for rides on her motorcycle because the low-pitched exhaust sounds bothered her. Rolling over in bed occasionally made her dizzy. Dizziness was most pronounced on exposure to loud sounds, and changes in altitude such as riding in an elevator were especially bothersome. While walking she needed to hold on to the wall or her spouse for support. Her symptoms were most pronounced when bending down. She reported an inability to prevent a fall when bending to pick up an object from the floor. Multiple sessions under the care of a physical therapist did not relieve her symptoms. Ear, nose and throat examination was normal, however the patient reported extreme nausea on left-sided pneumatic otoscopy, and a questionable left beating short-lived nystagmus was observed. Bedside vestibular testing and VNG were found to be normal on 9 August 2019. The Hennebert test was equivocal, but with the Tullio test the patient demonstrated pulsion to the right. cVEMP was normal on the right but was abnormal on the left side with increased amplitude and decreased threshold down to 65 dB nHL (Figures 2C1,C2). The gray-scale inversion technique on high resolution temporal bone CT scan raised the possibility of a left membranous stapes footplate. The patient consented to surgery and on 5 December 2019 underwent fat graft placement over the oval and round windows (Figures 2A,B). While her ear felt plugged following surgery her symptoms of disequilibrium resolved almost immediately. On 14 January 2020 pulsion was not elicited on Tullio testing. Auditory thresholds recovered completely to preoperative levels, and post-operative cVEMP testing demonstrated normal amplitude and threshold on the left side (Figure 2D). The patient's and her husband's impressions can be seen and heard in Videos 4, 5. The patient reports that she is almost completely back to normal. | gray-scale invert function ct scan, head trauma, hypermobile stapes, perilymph fistula, stapes footplate defect, third window syndrome, vertigo | Not supported with pagination yet | null |
PMC8549391_01 | Male | 52 | A 52-year-old painter presented to the outpatient department of a tertiary care teaching hospital with chief complaints of recurrent episodes of fever with chills throughout February 2021. He also complained of dull, aching, continuous, non-migratory pain in bilateral feet, the right knee, the right shoulder joint and the neck for the previous 20 days. This was accompanied by swelling of bilateral upper and lower limbs. The patient had a history of losing weight over the previous 4 years and uncontrolled diabetes mellitus for 8 years. He was also a heavy alcohol consumer (>5 drinks/day) and a chronic smoker. He was a resident of a rural district, Bhojpur, located in Bihar, East India, where he described himself as living in a kutcha house close to paddy fields. The patient belonged to a lower socioeconomic class corresponding to a score of 5 on a modified Kuppuswamy scale. There was no history of a similar disease in the past, or among the other family members. The patient also gave no history of trauma, tuberculosis or other respiratory complaints, prolonged antibiotic use, or surgery in the past.
On presentation, the patient had a temperature of 37 C, with a pulse rate of 78 beats min-1 and blood pressure of 98/72 mm of mercury. Examination revealed pallor and pitting oedema of the upper and lower limbs. On inspection, there was no erythema or discolouration of the skin over the limbs. Palpation of the knee and shoulder joint was acutely tender. The patient was unable to walk or abduct the right arm because of pain. Examination of other systems was unremarkable.
Random blood sugar on admission was 250 mg dl-1. Blood was collected for a complete haemogram, blood culture, renal function tests and viral serology. Haematological investigations revealed a total leukocyte count (TLC) of 17 000 microl-1, with 90.6 % neutrophils, and a platelet count of 38 000 microl-1. The patient had C-reactive protein (CRP) of 97.32 mg l-1 and glycosylated haemoglobin (HbA1C) of 13.53 %. Serum urea and creatinine were 53.5 and 0.98 mg dl-1, respectively, and the patient tested non-reactive for human immunodeficiency virus (HIV) and hepatitis B and C viruses. An ultrasound of the right lower limb revealed a 5.6 mm thrombus in the right saphenofemoral vein. A differential diagnosis of lower limb necrotizing fasciitis with deep vein thrombosis was made.
The patient was administered opioid analgesics to address excruciating joint pain. The antibiotics piperacillin/tazobactam, vancomycin and clindamycin were begun empirically for necrotizing fasciitis, in addition to insulin infusion and other supportive measures. However, within 48 h of admission, the patient became hypotensive and subsequently progressed to septic shock with acute kidney injury, requiring intensive care and inotropic support. Piperacillin/tazobactam was discontinued and the patient was started on meropenem 1 gm i.v. thrice daily.
Blood culture, collected soon after initial examination, flagged positive within 48 h of incubation. A Gram stain from the bottle showed bipolarly stained Gram-negative bacilli (Fig. 1). Within 48 h of incubation, growth on Blood and MacConkey agar showed medium-sized oxidase-positive colonies with dry margins and a metallic sheen. The organism was presumptively identified as Burkholderia pseudomallei by routine biochemical reactions and resistance to colistin, polymyxin B (300 units) and aminoglycosides, along with a sensitive zone size for amoxicillin/clavulanate. The identification was confirmed using the VITEK-II Compact system (bioMerieux, Marcy l'Etoile, France) with 98 % concordance. The isolate was uniformly susceptible to ceftazidime, meropenem, imipenem, doxycycline, and cotrimoxazole. The treating unit was promptly alerted about the organism. Antimicrobial therapy was revised by a multidisciplinary team consisting of physicians and microbiologists. The administration of injection meropenem (3 g/day) was continued, and injected vancomycin and clindamycin were stopped. Simultaneously, an urgent non-contrast computed tomography (CT) scan of the neck and thorax, and a contrast-enhanced CT of the abdomen, were planned to look for occult abscesses. Although the patient had no respiratory symptoms, radiological examination revealed multiple nodules in bilateral lungs with an abscess measuring 1.4x1.5x1.9 cm3 in the anterior segment of the right upper lobe, multiple soft tissue abscesses within muscles of the right shoulder joint, multiple prostatic abscesses and rim-enhancing splenic abscesses along with splenic vein thrombosis (Figs 2-4). Hence, the diagnosis was revised to disseminated septicaemic melioidosis with multiple deep organ abscesses and musculoskeletal involvement. The dose of injected meropenem was increased to 6 g/day, given the extent of the disease and the presence of deep organ abscesses. The patient showed gradual improvement over 1 week and was weaned off inotropes and intensive care. Urology and orthopaedic reference were sought for the prostatic abscesses, and possible septic arthritis of the knee joints, respectively. While a decision to allow spontaneous resolution of the prostatic abscess was taken, pig-tail drainage of the splenic abscess was considered. However, a day later, despite explaining the extent of the disease and the risk of fatality, the patient opted to be discharged. The patient was discharged on request following 14 days of intravenous meropenem. He was advised to continue treatment with intravenous meropenem for 4 more weeks, followed by an oral eradication therapy with cotrimoxazole for 3 months as recommended by the revised Darwin study consensus guidelines of 2020, and to maintain adequate glycaemic control. The patient was followed up telephonically a month after diagnosis. He had been compliant with intensive intravenous therapy and showed symptomatic improvement. | burkholderia pseudomallei, disseminated melioidosis, melioidosis | Computed tomography image (coronal view) showing a small lung abscess with air-fluid level (arrow) in the upper lobe of the right lung. Also, note the periarticular abscess around the right shoulder joint (arrowhead) that resulted from septic arthritis. |
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PMC5050361_02 | Male | 5 | At 4.5 years old, the child's height and weight were greater than 95th percentile, with weight disproportionately larger than height (Figure 2). His head circumference was at 90th percentile. He had a short forehead, well formed ears with fleshy lobes, a prominent brow, and a small dimpled chin. The obesity was associated with striae and inverted nipples. He had bridged palmar creases bilaterally, fifth finger clinodactyly on the left hand, and an increased space between the first and second toes.
At 4.5 years of age, the patient's bone age was 6.5 to 7 years, which is more than 2 standard deviations above the mean for his age. At 10 years of age, he had some pubic and axillary hair. His penis appeared small upon examination at both 10 and 15 years of age. At 15 years of age, the patient's height was 180.7 centimeters (90th percentile), weight was 150.8 kilograms (>97th percentile), and head circumference was 58 centimeters (75th-90th percentile). The BMI was 46.2, which is well above 99th percentile. Hormone studies were not available.
There was a family history of obesity, but not tall stature. The patient's father's BMI was 43.4 (obese), and his mother's BMI was 41 (obese). The patient's older brother's BMI was 26.2 (overweight). The patient's brother reportedly met his early developmental milestones appropriately. Subsequently, the brother had difficulties with speech, reading, and memory processing but was able to progress through school with assistance.
Genetic investigations including methylation studies for Prader Willi syndrome and Southern Blot for FMR1 for the patient were normal. Karyotype results were 46,XY,del(18)(q21.32q21.32). Sequencing of the MCR4 gene did not detect any mutations. A CGH microarray was undertaken to further define the patient's deletion.
Microarray evaluation using a 180k CGH microarray platform (hg19) gave a result of arr[hg19] 1p13.3 (109,336,197-109,779,618) x 3; 18q21.32q22.1 (56,201,352-62,696,664) x 1. The 0.463 Mb gain at 1p13.3 was described as a variant of uncertain significance and included the following genes: STBP3, AKNAD1, GPSM2, CLCC1, WDR47, TAF13, TMEM167B, SCARNA2, C1orf194, KIAA1324, SARS, and CELSR2. The 6.46 Mb loss at 18q is unique in size and location and includes the following genes: SERPINB3, MC4R , PMAIP1, SERPINB5, VPS4B, SERPINB2, MALT1, BCL2, LMAN1 , SCCHC2, PHLPP1, KDSR, SERPINB13, SERPINB10, HMSD, SEPRINB8, SERPINB7 , SERPINB11, TNFRSF11A , SERPINB4, SERPINB12, KIAA1468, RAX , CPLX4, ALPK2, SEC11C, ZNF532, CCB3E1 , GRP, CDH20, RNF152, and PIGN. Of the preceding list, the OMIM morbid disease genes are in bold. Deletion of MALT1, LMAN1, SERPINB7, TNFRSF11A, RAX, CCB3E1, and PIGN was not expected to have an effect on the patient as loss of function mutations need to be present in both copies of these genes in order to produce a disease state. Heterozygous mutations in Bcl-2 in mice have been shown to produce manic behavior, although this was not seen in our patient. Parental testing revealed that the 18q deletion was de novo. The patient's mother also had the 1p13.3 duplication.
Physical activity and diet management were recommended to manage the patient's obesity. He participated in a gym class and was counseled to minimize his excessive intake of sugar and unhealthy foods. In addition, the patient's family doctor was advised to monitor the patient for complications of obesity, including hyperinsulinemia, diabetes, and heart disease. | null | Not supported with pagination yet | null |
PMC2957978_01 | Male | 26 | Patient 1 was a previously healthy, 26-year-old Peruvian man who was evaluated in July 1985 for a 3-month history of periorbital pain, headaches, and periodic generalized tonic-clonic seizures. The initial neurologic examination was nonfocal, but subsequent computerized tomography scan showed a 5x5-cm enhancing mass in the left frontoparietal region associated with midline shift.
At the time of surgical biopsy, frozen section histology raised the possibility of a high-grade astrocytoma or lymphoma, prompting resection of a 3x3-cm well-circumscribed left frontal lobe mass. Final examination of pathologic specimens showed granulomas with multinucleated giant cells (Figure 1). Bacterial, fungal, and acid-fast bacilli stains were negative. Based on these pathologic findings and concern that the patient may have had tuberculosis, treatment with isoniazid, rifampin, and ethambutol was begun. Serologic tests for Histoplasma capsulatum, Blastomyces dermatidis, Coccidioides immitis, and Paracoccidioides brasiliensis were negative. Toxoplasma gondii serologic titers were weakly positive at 1:64.
On postoperative day 39, fungal tissue cultures became positive for a Brucella spp., preliminarily identified as B. melitensis. The patient's antimicrobial treatment was changed to tetracycline and rifampin and was continued for 2 months. An initial serologic titer for Brucella was positive at 1:160 by tube agglutination assay. A follow-up serologic titer obtained in January 1986 was negative (<1:20).
Three months before his initial evaluation, the patient had immigrated to the United States from Lima, Peru. His diet included regular consumption of unpasteurized cow or goat cheese (queso fresco) and occasional consumption of raw shellfish (ceviche). He denied eating other raw or significantly undercooked meat. He had frequently swum in the Pacific Ocean from December through March but recalled no direct contact with marine mammals. | null | Not supported with pagination yet | null |
PMC4648204_01 | Unknown | 3 | Our university is implementing a program for enhancing teaching that aims to ensure effectiveness through high quality design of learning outcomes and assessment regimes, multifaceted activities, and optimal delivery methods. The course chosen to spearhead a program for enhancing teaching across our university was SCI2010 Scientific Practice and Communication. The course deals with the nature and origins of science, ethical practice and science communication. This large, interdisciplinary unit is compulsory for all science students studying at the Melbourne and Malaysian campuses, or by distance education. There are approximately 1200 students (600 per semester) mostly in their second year of University and taking degrees in Physics, Biology, Chemistry, Biomedical sciences, Mathematics and Psychology. Students are, on average, 20.3 years old, with over one-third from homes where a language other than English is spoken (more at the international campus). A survey of graduates found that only one-fifth of students would have taken the subject if it was not compulsory, but in hindsight over two-thirds said they had learnt things not otherwise covered in their degree and that it should remain compulsory (unpublished data, The Faculty of Science, Monash University 2009). It is thus both challenging and rewarding to present the subject matter in a way that is intellectually engaging and relevant to students from a wide range of disciplines.
The course had always had a 'Quick links' section at the top of the page (as seen in Figure 2b). This guided the students to resources that they needed to access in a timely manner. These included Assessments, Lecture resources, Quizzes, and the highly rated, What's on this week? that linked directly to the relevant page with the weekly learning activities. The buttons had been used for the past few years, and only required minimal modification to reflect the new navigation system. The unit Introduction (which was already in the Unit Guide) was brought into the online course front and centre, presenting this unit in context in the wider course and emphasising the learning outcomes as they applied in practice.
There was an obvious need to change the weekly headings to something that best described the topic and give the student more clues and support for their learning. As propose, a well-designed structure underpinning the learning process will facilitate students' understanding of the concepts leading to successful outcomes. The section headings were changed from Week 1, Week 2 to topic names such as Is science special? Can we afford self-deception? Can scientists be bad? Each topic was presented with a consistent weekly structure to create expectations of learning activity. This structure included an introduction to the topic, the learning outcomes, and a pre-class activity to activate thinking for this week's concept, learning activities - Something to read, Something to do, Something to think about- a series of questions for reflection, and the link to the lecture slides.
As we worked through this makeover, it became obvious that by contextualising the topics with more supporting information and activity, we were actually accentuating the major themes of the unit. It must be emphasised here that at no point did the content change, but rather the way that the learning resources and activities were presented changed the focus from a list of resources to a more thematically contextualised, learner-centred structure. This caused a re-think in the delivery and a shift in the paradigm to where the online space was truly connected to the face-to-face interaction.
As a start, the design of the online space in Moodle was changed from collapsed topics to a more open setting. This different unit layout eschews the linear format, introduces images to guide the learner to different sections, whetting their appetite for further investigation. Each section in the new configuration has its own image and description to guide the students quickly to course material that they need ( Figure 3). This design and clear learning pathway was implemented to make obvious to the student the actions required to achieve specified learning outcomes. The learner is guided through scaffolded activities, discussions, opportunities for reflection, self-test quizzes, and extension activities if needed or desired. We believe that an altered learning landscape motivates the learners to engage with the prescribed materials and activities at a deeper level and reflectively participate in the learning experience. In doing this they are learning to become pro-active participants in their environment, actively reshaping their landscape to support on-going learning ( ).
For us, contextualising the learning means adding value to the materials and activities presented online; interacting with the learners through the instructions and guidelines; and being present in that space with them, similar to that described by . In order to get to the underlying purpose of each activity, the learning designer (BM) prompted the teacher (RG) by asking: "If you were to present this video/activity/article to read in a face-to-face class, what would you say by way of introduction?" This forced the teacher to really think about the context and that then shaped the writing surrounding the learning activities so that the purpose was crystal clear, and would make sense to the students, forestalling questions such as: Why am I doing this? What's the point of this?
The learning pathway was designed to guide the learner through clearly sign-posted themes and topics in order to help the students understand the progressive and cumulative building of knowledge; and to help them synthesise and apply the key concepts ( Figure 5). Students could, of course, access all the weekly resources through the quick links at the top of the page, and some did. However, our feedback and analytics of the hits per page suggest that most students took advantage of the learning opportunities presented in this format.
A typical layout and introduction for each 'lecture' activity is shown in Figure 6. At the top there is a very short introduction, followed by a very short video and a Moodle Choice activity. This was designed to stimulate thinking on the topic, and by voting the students had to consider the issue and act, thus activating their thinking on the new concept and preparing them for the new learning. The next step for students is to access the Lecture resources. Again, the information was organised in a consistent format, designed to fit on a single screen of a computer, (see Figure 4) incorporating a short introduction, a list of learning outcomes, and a list of things to do post-lecture, called ' Something to read' (content and further reading), 'Something to do' (a related activity) , 'Something to think about' (opportunity to reflect, extend and apply the learning.). The link to the lecture slides was at the bottom of the page.
In order for this blended model to be effective, all the tutors on the course were encouraged to participate in the online activities in private discussion forums (on-line and face-to-face) and bring those discussions into the classroom. The guided online activities were referred to and discussed in class, reinforcing to the students that the online space was valued as much as the face-to-face interaction. This seamless interaction in the online and face-to-face spaces highlighted to the students that the teachers were active in both spaces and the each mode was an essential element of the course delivery.
There were 763 students enrolled in the unit: 633 at the Melbourne campus in Clayton, 109 at the campus in Kuala Lumpur, Malaysia (where students do the same program but have their own lecturers) and 21 students taking the unit by distance education. Data on student responses to the new layout and structure was collected in four ways. Firstly, we determined how many students were accessing the material and participating in the non-compulsory pre-lecture choice activities. Secondly, an online survey was conducted in Week 9 of the teaching program (see Supplementary material for wording of the questions). Thirdly, observations of attendance and engagement, and the type of questions that students were asking during the lead up to the final examinations were made.
On average, 159 students took part in each pre-lecture poll, ranging from 415 in week 1 to 92 in the final week ( Table 1). Participation in the ten polls was completely optional, and attracted no marks. The weekly online revision quiz opened after the lecture and closed the evening before the lecture the following week. Students could make up to three attempts in this time. Students were rewarded with a 'participating mark' of 0.25% of the semester grade for attempting each quiz, but while they got feedback on their answers, no marks were given for getting the right answers. On average, there were over 1000 attempts at the quiz each week, which means that some students were attempting them multiple times.
"Your Moodle site is awesome! I wish all our units were like that."
"...By far my favourite moodle page of any subject."
There was the opportunity for students to provide open-ended responses (see Supplementary Data) as well as the ranking of specific aspects. Overall students were very positive about the changes:
Students were particularly positive to the questions about the navigation of the site, with 80.5% agreeing that the navigation was logical (Question 2), and the information easily accessible ( Figure 7). Students singled out the Quick Link buttons at the top of the page with 60.3% strongly agreeing that they liked being able to navigate the site using the buttons on the home page, and 55.2% strongly agreeing that is was easy to find information about the assignments. This was particularly rewarding, as a recurring complaint in student evaluations in past years was that it was hard to find out what was required for the assignments.
"The start buttons made for excellent navigation..."
"It [the quick link menu] makes it easy to find the quizzes, information for workshops and information from lectures. Moodle isn't always easy to navigate so this has definitely helped."
"I didn't like the organisation of the course content on Moodle. I much prefer the normal unit layout with everything on one page under different subheadings. It was often quite annoying having to click through many different pages in order to find information."
Of course, not everyone liked the new layout. The comment (below) highlighted one of the problems that we anticipated: if information is only accessible via the themes, then more clicking is required. It is good web design to be able to access the same material in several different ways, and this was incorporated into the design, but clearly this was not immediately obvious to everyone:
The major focus of the revisions was the lecture pages, while the workshop pages had only minimal information on them. Interestingly, this could be detected by the student responses. Over 55% of students strongly agreed and a further 30% somewhat agreed that " the lecture support pages helped me understand the lectures..." but only 29% strongly agreed with the statement that "that " the workshop support pages helped me to get more out of the workshops". Other comments on the changes included:
"Really liked the things to read, do and think about sections for every week. Really helped me keep on track with the subject and what is required."
"Workshop resources should be linked to the lectures rather than having a separate tab."
"I found the course content to flow logically from week to week."
"Suggest you make the slides more text rich? The way they are you have to listen to the whole lecture to work out what it is about"
The Moodle book was developed in response to students wanting more specific information; something particularly important in this course as there isn't a textbook. Reluctant to move from good design and communication practice (few words, lots of images), I transferred and edited existing written materials into the on-line Moodle Book format. For example, feedback from 2014 included the following:
"please put more explanation and sentences in the slides instead of a bunch of images"
Not everyone worked out that this type of information was now available via the Moodle Book, as one student commented in the present survey:
"I like the moodle book however it should be supplied by a pdf."
As so often happens in education, students like what you've done and then want more of it. For example, the Moodle book is the first one of its kind in the Faculty of Science, but one student commented:
In a typical semester lecture attendance can fall below 20% by the end of semester. Although we did not collate the data formally, counts of students at the end of the implementation program showed a shift closer to 25%. As expectations rise, we expect attendance to further improve. Why does this matter? Lectures should be the place where we inspire, direct and interact with students. By contextualising lectures, and making them part of a blended learning program, students should be better equipped to engage intellectually, and not be passive recipients of information.
" What are we supposed to know about the lectures on....?"
Students in this course actively engage in Discussion forums during semester and in the lead up to the examinations. This semester there were far fewer questions asking for clarification about the objectives of each topic, and more questions about the application, reflecting deeper learning. For example, comments along the lines of:
"Just wanted to clarify one of the examples on....given in the lecture..."
Were replaced by comments such as:
The learning designer (BM) and the teacher (RG) met for an hour every few weeks at first and then weekly as momentum gathered over a three-month period. At first, discussion was focused around the nature of learning and how best to facilitate that in an online environment. A teaching associate and education technologist (MH) was employed who would implement our ideas into the LMS. The learning designer modelled the design in a separate "trial" shell by importing the course's artefacts and building samples of the Assessment block, the Choice activity, the contextualisation of activities and resources. MH implemented the design ideas into the LMS, incorporating design elements to simplify and enhance learner experience. RG then re-worked the content to suit the new design and wrote introductions and other supporting and instructional text to guide the learner through the material. We were able to access funding through the Faculty of Science to pay for approx. 50 hours of support for MH to build the course according to the specifications and source images for each section and videos for the pre-class activities and to build the topic quizzes (including the introduction of new styles of question), which proved to be very popular with students for revision.
We now have templates for other teaching coordinators to use to guide them through the process. Other units in the Faculty of Science have adopted this design and other faculties are also using a modified version of the unit template and branding it as their own. The topic and lecture templates are in the form of Word documents for those unfamiliar with working in the Moodle LMS and these templates have been developed as Pages in a course called "Model Moodle" for others at our institution to import into their own course and edit. With these resources, unit enhancements similar to our own can be implemented by the unit coordinator with some support and training, and indeed this is already happening. There was no multimedia magic, just looking at the LMS differently and seeing the possibilities. This makes it scalable and easy to replicate. The hard part is in the shift in mind-set to a more interactive and contextualised presentation of learning materials to activate deeper thinking and conceptual development. | blended learning, moodle, educational design, higher education, on-line learning, science communication | Not supported with pagination yet | null |
PMC3920433_01 | Female | 19 | A 19-year old female was admitted to our hospital because of a sudden onset fever and cough. She had developed the cough, fever and progression of dyspnea two days before admission. Antibiotic treatment prior to hospitalization was not effective for the clinical symptoms. She had started to smoke 20 cigarettes per day two weeks before the admission. She had a history of pollinosis, but no previous history of bronchial asthma. On admission, her temperature was 39.4 C. Auscultation revealed wheeze in the bilateral lung fields.
An arterial blood gas analysis on room air revealed a pH of 7.434, PaO2 of 58.1 torr and PaCO2 of 34.2 torr, indicating hypoxemia. A chest radiograph revealed diffuse bilateral infiltrates and pleural effusion in the right lung, as shown in Fig. 1. The patient's peripheral white blood cell (WBC) count was 18,600 cells/mm3, with 84.4% neutrophils, 11.8% lymphocytes and 1.0% eosinophils. The serum C-reactive protein was 11.5 mg/dl. Her serum immunoglobulins (Ig) were: IgG, 1048 mg/dl; IgA, 166.0 mg/dl; IgM, 199.0; IgE, 196.8 U/ml. Bronchoalveolar lavage fluid (BALF) was obtained from right B5 area on the third hospital day. The total cell count in the BALF was 98.0 x 104/ml, which contained 5.6% neutrophils, 12.0% lymphocytes and 66.6% eosinophils. The CD4/CD8 lymphocytes ratio in the BALF was 1.26. Cultures of the BALF proved negative for bacteria and fungi. A specimen obtained from transbronchial lung biopsy (TBLB) demonstrated eosinophilic infiltration with fibrin exudates into the air space and edematous alveolar walls, indicating eosinophilic pneumonia.
On the fourth hospital day, her chest radiograph and symptoms had remarkably improved without corticosteroid treatment. Her hypoxemia had been gradually improving, and her SpO2 was 97% under room air on the forth hospital day. The peripheral eosinophil count, which had been 186 cells/mm3 on admission, increased gradually to 1400 cells/mm3 on the seventh hospital day. Although the eosinophilia was prolonged over 1 month, the peripheral eosinophil count decreased to 504 cells/mm3 2 months after the development of AEP. The peripheral lymphocyte count also increased from 2195 cells/mm3 on admission to 3367 cells/mm3 on the seventh hospital day, and decreased to 2720 cells/mm3 2 months after the development of AEP. Therefore, the peripheral eosinophil count appeared to fluctuate in parallel with the peripheral lymphocyte count (Fig. 2).
The patient was discharged on the 13th hospital day. She quit smoking and has not resumed. Three months later, she continued to be asymptomatic. She reported having smoked two kinds of cigarettes. The lymphocyte stimulation tests (LSTs) for the both kinds of cigarette smoke extract were negative.
A cytokine analysis of the serum was performed on admission and on the 13th hospital day, and a cytokine analysis of the BALF was performed on the third hospital day (Fig. 3). The levels of IL-6, IL-5, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES) and eotaxin in the serum on admission were 28.7 pg/ml, 2590 pg/ml, 98.5 pg/ml, 20000 pg/ml and 171 pg/ml, respectively. The cytokine analysis of the serum performed on the 13th hospital day revealed that the levels of IL-6, IL-5, IL-4 and eotaxin had decreased to 1.0 pg/ml, <5.0 pg/ml, 71.9 pg/ml and 104 pg/ml respectively, but that RANTES had increased to 78900 pg/ml. The levels of IL-6, IL-5, IL-4, RANTES and eotaxin in the BALF were 19.4 pg/ml, 883 pg/ml, 6.0 pg/ml, 42.1 pg/ml and 59.3 pg/ml, respectively. The levels of all cytokines in the BALF were lower than those in the serum obtained on admission. In particular, the level of RANTES in the BALF was much lower than that in the serum. | acute eosinphilic pneumonia, cigarette smoking, rantes | Chest X-rays and CT scans. A. The chest X-ray on admission showed bilateral ground-glass opacification which was relatively right lung dominant. |
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PMC3920433_01 | Female | 19 | A 19-year old female was admitted to our hospital because of a sudden onset fever and cough. She had developed the cough, fever and progression of dyspnea two days before admission. Antibiotic treatment prior to hospitalization was not effective for the clinical symptoms. She had started to smoke 20 cigarettes per day two weeks before the admission. She had a history of pollinosis, but no previous history of bronchial asthma. On admission, her temperature was 39.4 C. Auscultation revealed wheeze in the bilateral lung fields.
An arterial blood gas analysis on room air revealed a pH of 7.434, PaO2 of 58.1 torr and PaCO2 of 34.2 torr, indicating hypoxemia. A chest radiograph revealed diffuse bilateral infiltrates and pleural effusion in the right lung, as shown in Fig. 1. The patient's peripheral white blood cell (WBC) count was 18,600 cells/mm3, with 84.4% neutrophils, 11.8% lymphocytes and 1.0% eosinophils. The serum C-reactive protein was 11.5 mg/dl. Her serum immunoglobulins (Ig) were: IgG, 1048 mg/dl; IgA, 166.0 mg/dl; IgM, 199.0; IgE, 196.8 U/ml. Bronchoalveolar lavage fluid (BALF) was obtained from right B5 area on the third hospital day. The total cell count in the BALF was 98.0 x 104/ml, which contained 5.6% neutrophils, 12.0% lymphocytes and 66.6% eosinophils. The CD4/CD8 lymphocytes ratio in the BALF was 1.26. Cultures of the BALF proved negative for bacteria and fungi. A specimen obtained from transbronchial lung biopsy (TBLB) demonstrated eosinophilic infiltration with fibrin exudates into the air space and edematous alveolar walls, indicating eosinophilic pneumonia.
On the fourth hospital day, her chest radiograph and symptoms had remarkably improved without corticosteroid treatment. Her hypoxemia had been gradually improving, and her SpO2 was 97% under room air on the forth hospital day. The peripheral eosinophil count, which had been 186 cells/mm3 on admission, increased gradually to 1400 cells/mm3 on the seventh hospital day. Although the eosinophilia was prolonged over 1 month, the peripheral eosinophil count decreased to 504 cells/mm3 2 months after the development of AEP. The peripheral lymphocyte count also increased from 2195 cells/mm3 on admission to 3367 cells/mm3 on the seventh hospital day, and decreased to 2720 cells/mm3 2 months after the development of AEP. Therefore, the peripheral eosinophil count appeared to fluctuate in parallel with the peripheral lymphocyte count (Fig. 2).
The patient was discharged on the 13th hospital day. She quit smoking and has not resumed. Three months later, she continued to be asymptomatic. She reported having smoked two kinds of cigarettes. The lymphocyte stimulation tests (LSTs) for the both kinds of cigarette smoke extract were negative.
A cytokine analysis of the serum was performed on admission and on the 13th hospital day, and a cytokine analysis of the BALF was performed on the third hospital day (Fig. 3). The levels of IL-6, IL-5, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES) and eotaxin in the serum on admission were 28.7 pg/ml, 2590 pg/ml, 98.5 pg/ml, 20000 pg/ml and 171 pg/ml, respectively. The cytokine analysis of the serum performed on the 13th hospital day revealed that the levels of IL-6, IL-5, IL-4 and eotaxin had decreased to 1.0 pg/ml, <5.0 pg/ml, 71.9 pg/ml and 104 pg/ml respectively, but that RANTES had increased to 78900 pg/ml. The levels of IL-6, IL-5, IL-4, RANTES and eotaxin in the BALF were 19.4 pg/ml, 883 pg/ml, 6.0 pg/ml, 42.1 pg/ml and 59.3 pg/ml, respectively. The levels of all cytokines in the BALF were lower than those in the serum obtained on admission. In particular, the level of RANTES in the BALF was much lower than that in the serum. | acute eosinphilic pneumonia, cigarette smoking, rantes | Chest X-rays and CT scans. B. A chest CT on admission showed diffuse ground-glass opacification in the right lung, patchy opacification in the left lung, and a small amount of pleural effusion in the right lung, consist with the opacification on chest X-ray. |
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PMC10076740_01 | Female | 8 | An 8-year-old girl was transferred to our hospital due to hyperleukocytosis, which was incidentally discovered as she did not exhibit any symptoms. Upon physical examination, we found severe hepatosplenomegaly, with her liver and spleen palpated at about 9cm and 7cm, respectively, below the costal margin. Initial peripheral blood counts showed the following results: white blood cells (WBCs) of 198 x 109/L (normal: 4-10 x 109/L) with 1% blast, hemoglobin of 10.0 g/dL (normal: 11.0-14.5 g/dL), and platelets of 352 x 109/L (normal: 150-450 x 109/L). The bone marrow aspirate smears revealed hypercellularity with a high myeloid: erythroid ratio (higher than 20:1), and approximately 5% of all nucleated cells were lymphoblasts. Karyotyping and fluorescence in situ hybridization (FISH) of a bone marrow sample were positive for t(9;22)(q34;q11), leading to a diagnosis of CML-CP. The patient's EUTOS Long-Term Survival score was 1.229, indicating that she belonged to the low-risk group. We started on dasatinib (60 mg/m2, once daily) for initial TKI therapy.
Three months after treatment, the patient exhibited both a complete hematologic response (CHR) and a complete cytogenetic response (CCyR). Quantitative polymerase chain reaction revealed a BCR::ABL1 transcript level of 2.55% on the international scale (IS) at 3 months, indicating an optimal response. However, the therapy did not yield the milestones of an optimal response thereafter: 1.6% IS at 6 months and 0.9% IS at 12 months. Although her TKI response was at the "warning" level, we decided to maintain her on dasatinib instead of changing the medication because the BCR::ABL1 transcript levels were constantly decreasing ( Table 1 ).
Fourteen months after treatment, the patient was admitted due to visual disturbance. Fundoscopy revealed bilateral optic disc edema with a macular star, and brain MRI revealed diffuse swelling of both optic nerves without clear leptomeningeal and parenchymal abnormalities ( Figure 1 ). Based on our initial assessment of dasatinib-induced optic neuropathy, we decided to discontinue dasatinib and start methylprednisolone pulse therapy. Within a month, her subjective symptoms and visual acuity improved. At 15 months from the start of treatment, the patient's BCR::ABL1 transcript level in the bone marrow remained at the warning level (0.3% IS) but had decreased from previous time points.
Two months later, the patient returned to our hospital due to severe and aggravated headaches that had persisted for two weeks. Upon examination, cerebrospinal fluid (CSF) immunophenotyping revealed a large proportion of abnormal cell populations, with approximately 89% lymphoblasts expressing CD20, TdT, and PAX-5 (negative for CD3 and MPO). The bone marrow was free of leukemic infiltration and the patient maintained a CHR and CCyR, indicating that she was experiencing an isolated CNS lymphoblastic crisis. At this time, the MRI showed an improvement in optic nerve swelling compared to the previous MRI.
She was begun triple intrathecal (ITT) chemotherapy (methotrexate, cytarabine, and hydrocortisone) and the lymphoblast was eliminated after single dose of ITT chemotherapy. Hence, she was administered an additional five doses of ITT chemotherapy and a subsequent allogeneic HSCT was planned ( Figure 2 ). Since she was still off dasatinib and had an isolated CNS relapse, we decided to resume dasatinib, which is known to penetrate the CNS, instead of switching to another TKI until allogeneic HSCT. The patient's BCR::ABL1 transcript level was 0.6% IS at the time of HSCT.
The patient underwent peripheral blood stem cell transplantation from a 1-allele-mismatched (HLA-A), unrelated donor. The preparative regimen consisted of myeloablative conditioning, with total body irradiation (TBI) of 1,320 cGy (from days -7 to -4), cyclophosphamide (120 mg/kg from days -3 to -2), and rabbit antithymocyte globulin (3.75 mg/kg from days -3 to -1). The infused CD34+-cell dose was 10.3 x 106 cells/recipient kg. She developed grade 2 graft-versus-host disease in the gut, which was well tolerated with a short course of steroid treatment. Full donor chimerism was detected on day 28 post transplantation, and the BCR::ABL1 transcript levels in the peripheral blood at 1, 3, and 6 months after transplantation were 0% IS without TKI therapy. | dasatinib, cerebrospinal fluid study, isolated central nervous system blastic crisis, pediatric chronic myeloid leukemia, tyrosine kinase inhibitor induced optic neuropathy | Not supported with pagination yet | null |
PMC3395676_01 | Male | 22 | A 22-years-old male was diagnosed as a case of very severe aplastic anaemia seven months back when he presented with fever and gum bleeding. He had HLA matched sibling and underwent allogenic peripheral blood stem cell transplantation. Conditioning regimen included fludarabine 30mg/m2 for 6 days and cyclophosphamide 60mg/m2 for 2 days. Graft versus host disease (GVHD) prophylaxis included anti-thymocyte globulin 30mg/kg/day for 4 days, methotrexate (10mg/m2) on day +1, +3 and +6, and cyclosporine 100mg twice daily intravenously followed by oral cyclosporine with dose adjusted according to plasma cyclosporine levels (between 150-300ng/ml). He engrafted on day +9 (absolute neutrophil count >0.5x109/l and unsupported platelet count > 20x109/l). Two months post transplant patient noticed a small painless nodular swelling over the plantar surface of right foot. He was on cyclosporine at that time. There was no history of trauma or thorn prick injury. The swelling progressively increased in size in next two months with appearance of two discharging sinuses (Figure 1). Radiograph of right foot revealed soft tissue radio-opacity without involvement of underlying bony structures. There was discharge of black grains which on KOH mount examination under microscope (40x magnification) revealed presence of septate hyphae. The culture of the discharged granules in Sabouraud's dextrose agar (SDA) grew Madurella mycetomatis (Figure 2) after an incubation for 12 days. The patient was started on voriconazole (400 mg orally twice daily on first day followed by 200 mg twice daily). The lesion was completely excised one week later. Biopsy smears showed distinct brown-black colonies of the fungus having branching and septate hyphae embedded in matrix like material against a mixed inflammatory background. Voriconazole was continued and there is no recurrence of lesion three months post excision.
With the increasing number of patients undergoing transplantation, newer fungal infections are emerging and posing a diagnostic and therapeutic challenge. Mycetomatis is a chronic infection which initially involves cutaneous areas and progresses to involve deeper structures. Mycetoma presents as a slow growing indolent infection characterised by tumaefaction and multiple discharging sinuses. The etiological agents can be a variety of fungal agents (eumycetoma) or bacteria belonging to the actinomycetes group (actinomycetoma). Madurella mycetomatis is the worldwide predominant eumycetoma, followed by Scedosporium apiosperma, Scedosporium prolificans, and Madurella grisea. These fungi account for approximately 95% of eumycetoma cases. Madurella mycetomatis (black grain mycetoma) is the most common eumycetoma in India. It is also endemic in Sudan, Central and South America and Indonesia. In contrast, Scedosporium (white grain mycetoma) is the commonest eumycetoma in North America. It is the most commonly reported eumycetoma in transplant recipients, which is associated with a high rate of dissemination and a high mortality. There is no data of madurella infection in transplant recipients except for two reported cases who received immunosuppressive therapy for renal transplantation (infected by Madurella grisea and Madurella mycetomatis, respectively). With the increasing number of patients undergoing transplants in tropical and subtropical countries, Madurella mycetomatis will be an emerging fungal infection in such a group of population.
The differential diagnosis of eumycetoma lesions include actinomycetoma, botryomycosis, cutaneous tuberculosis, fungal diseases such as blastomycosis and coccidioidomycosis, and cutaneous nocardiosis. An early diagnosis is essential since the disease has a progressive course with extension and damage to deeper tissues and internal organs, particularly more so in immunocompromised patients. Discharging sinus tracts are very characteristic of mycetoma and are helpful in making the clinical diagnosis. The cytological diagnosis of eumycetoma can be as accurate as histological diagnosis, and techniques such FNAC as well as imprint smears are simple, inexpensive and fairly reliable techniques without any obvious disadvantages.
Early surgery can be curative for a small, localized eumycetoma lesion amenable to total excision and has been considered as a standard of care for such patients. Medical therapy of nonresectable or disseminated disease in immunocompromised patients is ineffective and may require aggressive debridement. Ketoconazole has been found effective for mycetoma caused by M. mycetomatis in at least 70% cases but is not an effective treatment for eumycetoma caused by Scedosporium species. The new second generation triazoles, including voriconazole and posaconazole have been tried as potential agents for eumycetoma, with some success.
Our patient developed nodular lesion on the plantar surface of right foot two months post transplant which slowly progressed and resulted in discharging sinuses. Biopsy revealed infection by M. mycetomatis. This is probably the first reported case of M. mycetomatis infection in a patient following allogenic hematopoietic stem cell transplantation. Early complete excision of the lesion resulted in complete cure. With increasing number of patients undergoing stem cell transplantation in tropical countries, eumycetoma caused by M. mycetomatis is one of the emerging fungal infections among transplant recipients, because of prolonged duration of immunosuppression. Since the fungus has poor response to antifungal drugs, early surgical debridement is very essential before the infection spreads to involve deeper structures. | null | Not supported with pagination yet | null |
PMC5379789_01 | Female | 48 | This 48-year-old female came with insidious-onset gradually progressive, continuous, dull aching type of pain on the right side of the neck radiating to the vertex region for 3 months. H/o weakness of all the four limbs along with tingling and numbness (Left >Right) were noted for 1 week, which was associated with bladder retention for 3 days. Motor examination showed increased tone in all four limbs. Power on the right upper limb was 4/5, power on the left upper limb was 0/5, lower limbs bilaterally was 3/5, left plantar was up going, sensory examination revealed decreased sensation over the left C2 dermatome and all modalities decreased below C2. X-ray of the cervical spine showed osteolytic destruction of the C2 body with subluxation of the C1 and C2 complex over C3 [Figure 1]. Magnetic resonance imaging (MRI) of the cervical spine showed kyphosis of the cervical spine with destruction of the C2 vertebral body along with pathological fracture. MRI also showed that the C2 vertebral body was showing T1 hypointense, T2 hyperintense lesions with posterior displacement of the severely compressed spinal cord [Figure 2]. Differential diagnosis of the expansile C2 vertebral body in immunocompetent and immunodeficiency patients is enumerated in Table 1. Preoperatively, our presumptive diagnosis was C2 vertebral body tuberculosis. The patient underwent decompression of the C2 lesion through the C2 right pedicle with occipito-C1-C3 lateral mass screws fixation (vertex medtronic system) [Figure 3]. Lesion anterior to the cord was reached by a transpedicular approach and decompression was performed. The lesion was pinkish grey, firm and moderately vascular and was destroying the C2 vertebral body. Preoperative and intraoperative opinion was tuberculoma; therefore, safe maximal resection was performed instead of complete removal. The patient improved symptomatically in power in the left upper limb and lower limb over the next 1 week duration from 0/5 to 4+/5. Histopathological examination of the tumor tissue showed spindle cells arranged in whorls and fascicles with proliferation of smooth muscle cells surrounding the blood vessels. Spindle cells showed eosinophilic cytoplasm with elongated nuclei with blunt ends. There was moderate cellularity, minimal atypia, inconspicuous mitosis and no evidence of necrosis [Figure 4a and b]. The tumor cells stained positively for smooth muscle actin, desmin and vimentin and negative for epithelial membrane antigen, S-100, Cluster of differentiation 34, estrogen and progesterone receptors, confirming the diagnosis of the leiomyoma [Figure 4c and d] and excluding the other possible lesions like meningioma and schwannoma. The patient was evaluated with ultrasound abdomen and contrast tomogram of the chest, abdomen and pelvis to rule out other possible lesions in the lung, intestines and uterus. Second surgery (trans-oral) was planned based on histopathology for complete removal of the tumor, which was postponed because of drastic improvement in myelopathy features. Postoperative MRI at 1 year showed residual tumor without cord compression [Figure 5], and she was asked for regular follow-up for any recurrence of symptoms. | acquired immunodeficiency syndrome, benign metastasizing leiomyoma, immunocompetent, primary leiomyoma | Not supported with pagination yet | null |
PMC3296495_01 | Female | 29 | A 29-year-old healthy woman presented to the emergency department with complaints of fever, chills and malaise for one week. She had been taking ibuprofen at home with no relief. She also noticed swelling in her neck bilaterally. There was no history of recent travel, sick contacts or exposure to people with tuberculosis. She denied dysuria, cough, diarrhea, shortness of breath, chest pain, menorraghia, night sweats or weight loss. She has been in a monogamous relationship for many years. There was no family history of lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis or any other rheumatologic disorders. She did not take any prescription or herbal medications. Social history was negative. Vital signs in the emergency department revealed a temperature of 103.2 F and a pulse of 113. Physical exam was normal except for bilateral anterior and posterior cervical, pre and post-auricular, submandibular, submental and right axillary lymphadenopathy. Initial laboratory studies revealed white blood cell count-3000 th/mm3, hemoglobin-8.8 g/dL, platelets-273 th/mm3 and mean corpuscular volume-66.2 mcm3. Chest x-ray was normal. Subsequently, she was admitted to the inpatient floor with persistent fevers and lymphadenopathy. Further laboratory studies revealed anemia of chronic disease. Hemolytic work-up was negative. Hemoglobin electrophoresis revealed no evidence of beta thalessemia. HIV, EBV monospot, Toxoplasma, and CMV serologies were negative. The patient continued to experience high fevers with rapidly increasing diffuse lymphadenopathy and further laboratory testing was ordered. Peripheral blood flow cytometry revealed no monoclonal B cell population that was identified and no evidence of paroxysmal nocturnal hemoglobinuria. The throat culture revealed beta hemolytic streptococcus and she was prescribed penicillin. CT scans of the chest, and abdomen/pelvis with intravenous contrast revealed enlarged bilateral axillary lymphadenopathy measuring up to 2.7 cm in largest dimensions. CT scan of the neck with intravenous contrast showed diffuse enhancing lymphadenopathy involving all neck levels, soft tissues and axillae bilaterally. Surgery consultation was obtained for the consideration of an excision lymph node biopsy. Further laboratory studies revealed an elevated IgG level. Antinuclear antibody and anti-double stranded DNA testing were negative. beta2 microglobulin level was elevated. Angiotensin-converting enzyme level was normal. She underwent excisional lymph node biopsy of the left cervical lymph node and was discharged home with instructions to take acetaminophen if she had recurrent fevers. The pathology report of the lymph node revealed lymphoid tissue with extensive geographic necrosis (necrotizing histiocytic inflammation) suggestive of Kikuchi's disease (Fig. 1). There was no evidence of infection in the lymph node specimen. The patient was informed of the diagnosis and told to return to the outpatient clinic for follow-up evaluation.
One month later, the patient presented to the outpatient clinic. The fevers had resolved and the lymph nodes had markedly reduced in size to less than a centimeter clinically. The hemoglobin was improving. She had further work-up to search for an identifiable cause of her condition. Serologic testing for human herpes virus 6, human herpes virus 8, and respiratory virus panel were negative except for an elevated parvovirus IgG level. Repeat HIV testing was also negative. She was also referred to the rheumatology clinic because she began experiencing morning stiffness. On a three month follow-up visit, she continued to be afebrile and the lymphadenopathy and microcytic anemia had resolved. Although the microcytic anemia had resolved, she was recommended to undergo a colonoscopy and upper endoscopy to evaluate the etiology of the microcytic anemia. Laboratory testing done in the rheumatology clinic revealed no evidence of any rheumatologic conditions. | histiocytic necrotizing lymphadenitis, kikuchi fujimoto disease, kikuchi’s disease, cervical lymphadenopathy | Not supported with pagination yet | null |
PMC4773054_01 | Male | 50 | A 50 year old male was referred to a tertiary cancer hospital. On inquiry, the patient revealed a painful, non healing ulcer on the cheek, since one month. He was a habitual smoker; his medical history was non-significant and the neck was negative for lymph nodes. Clinical examination revealed a diffuse ulcero-indurative lesion extending from the left lip commissure to the left buccal mucosa (A and B). A biopsy was performed at the buccal mucosa and the findings confirmed the absence of malignancy, but it rather described granulomatous tissue admixed with multinucleated foreign body gaint cells and inflammatory cell infiltrate. Considering the granulamatous nature, the lesion was rebiopsied and Ziehl Neelsen stain was applied; it clearly indicated a tuberculous etiology. Sputum was positive for Acid Fast Bacilli (10-99AFB/100 Field, grading 1+). Postero-anterior chest radiograph showed obliteration of right CP angle (pleural thickening), irregular fibrotic lesions and calcifications in both upper and middle lobes (sequelae of old koch's). Interestingly, this patient never had any symptoms of pulmonary tuberculosis. Though the incidence of oral lesions in tuberculosis is low, it should be included in the differential diagnosis of atypical oral lesions and oral squamous cell carcinoma. | oral tuberculous ulcer, atypical oral lesions, oral cancer | Not supported with pagination yet | null |
PMC8421174_01 | Female | 72 | A 72-year-old woman presented to our medical center with an altered mental status having suffered a fall. She had a history of primary hypothyroidism for many years treated with a stable dose of levothyroxine 0.075 mg/d. She was clinically euthyroid without tremors, palpitations, tachycardia, or other findings suggesting thyrotoxicosis. A pathologic fracture of her right humerus eight years before had led to a diagnosis of multiple myeloma with an IgG kappa M spike paraprotein. She received chemotherapy and went into remission. However, a recent reexacerbation had occurred, and she was being considered for further therapy. Routine admission labs revealed hematocrit 20.9% (normal 38-47%), sodium 132 mmol/L (136-145), potassium 4.0 mmol/L (3.5-5.1), chloride 104 mmol/L (98-107), urea nitrogen 45 mmol/L (20-31), and creatinine 2.8 mg/dL (0.6-1.0). Oncologic studies were consistent with multiple myeloma with an M spike kappa IgG paraprotein: total protein 10.1 g/dL (5.7-8.2), albumin 1.8 g/dL (3.4-5.0), and serum albumin: globulin ratio: 0.22 (0.60-1.50). Serum protein electrophoresis revealed gamma globulin 5.8 g/dL (0.8-1.7), kappa chain 9270 mg/L (3.3-19.4), Lambda chain 9.3 mg/dL (5.7-26.3), K/L ratio 996.7 (0.26-1.65), and B2:macroglobulin: 17.9 mg/L (<or = 2.51).
Thyroid biochemistry (Table 1) on presentation performed with the Siemens Atellica chemiluminescent immunoassay kit reported a slightly high TSH of 6.27 uIU/mL (normal 0.55-4.78) with normal total T4 of 4.5 mug/dL (3.2-12.6) and free T4 1.22 ng/dL (0.89-1.76). However, total T3 was markedly elevated at >600 ng/dL (60-181). Tests for anti-ThyroPerOxidase (AntiTPO), anti-ThyroGlobulin (antiTG), Thyroid-Stimulating Immunoglobulin (TSI), and Human Anti-Mouse Antibodies (HAMA) were within normal limits at <1 IU/mL (<9), <1 IU/mL (<1), <89% (<140), and <56 ng/mL (<74), respectively. Assay for anti-T3 antibodies was negative using a proprietary chemiluminescent competitive immunoassay procedure performed by Quest/Nichols Laboratories. Repeat testing on the Siemens Atellica platform again reported an elevated TT3 >600 ng/dL. Reverse T3 (Thermo Aria platform) was normal at 21 ng/dL (8-25), while results for TSH, total T4, and free T4 were similar to those reported previously. Free T3 was low at 1.7 (2.3-4.2 pg/ml (Siemens Advia kit) consistent with Euthyroid Sick Syndrome. 14 months earlier, her thyroid biochemistry was reported to be normal using the Roche Cobas chemiluminescent immunoassay kit with total T3 82 ng/dL (80-200). Thyroid Hormone-Binding Protein (THBP) electrophoresis was normal: TBG 14.3 mcg T4/dL (10.3-24.9), albumin 16.6 mcg T4/dL (11.5-34.1), and transthyretin (prealbumin) 69 mg T4/dL (48.8-70.4). Follow-up testing on the Roche Cobas platform again reported normal total T3 47.4 ng/dL (Table 1). Polyethylene glycol (PEG) precipitation was planned, but the patient expired before it could be accomplished.
We conclude that the factitious elevation in TT3 was most likely due to assay interference from the documented multiple myeloma paraprotein as well as differences between the test platforms used. | null | Not supported with pagination yet | null |
PMC8832325_01 | Male | 21 | Adam was a 21-year-old white British man with a 2% total body surface area (TBSA) full-thickness flame burn to his hand following a workplace accident six months before the intervention. He was employed full-time and was living with his partner at the time of the accident. After the accident, Adam developed post-traumatic stress disorder (PTSD), which had been treated successfully through trauma-focused psychological therapy by the second author (AT). In addition, Adam developed appearance anxiety due to scarring, and treatment for this began after his symptoms of PTSD had reduced to subclinical levels, as determined by the treating clinical psychologist (AT) and his self-report. He did not have a history of psychological problems before the accident but he reported that he had always had a degree of poor body image but that this had never impacted on his daily functioning. He worried about how others would perceive his hand, covered his scars, avoided holding hands with his partner and withdrew socially. This negatively impacted his relationship and social life. Adam received eight sessions of ACT. He cancelled and rearranged four sessions and had no non-attendances. | act, acceptance and commitment therapy, appearance anxiety, burns, disfigurement, necrotising fasciitis, scarring | Not supported with pagination yet | null |
PMC8832325_02 | Male | 26 | Paul was a 26-year-old white British man who sustained 8% TBSA mixed-depth burns to his face and hands during a workplace welding accident 13 months before the intervention. He had been working full-time in the welding industry before the accident and lived with his partner and pre-school daughter. He had no history of psychological difficulties. After the accident, Paul developed PTSD, which had been treated successfully through trauma-focused psychological therapy by the second author (AT). Before the intervention for his appearance anxiety, Paul's symptoms of PTSD were in the subclinical range and not impacting upon any area of his life. Paul experienced appearance anxiety associated with scarring on his hands and pigmentation changes to his face. He was troubled by thoughts about others judging him negatively and worried others would ask questions and that he would not be able to manage social exchanges. He spent excessive amounts of time checking and concealing his scarring by clothing, gloves and make-up. He was isolating himself, avoiding public places and had stopped doing meaningful activities with his young daughter, such as taking her to nursery, swimming and dance lessons. Paul received nine sessions of ACT. He cancelled and rearranged four sessions and had no non-attendances. | act, acceptance and commitment therapy, appearance anxiety, burns, disfigurement, necrotising fasciitis, scarring | Not supported with pagination yet | null |
PMC4392528_01 | Male | 25 | A 25-year-old male, a worker in a garment factory, presented with complaints of band like feeling in the upper abdomen, not associated with any abdominal or back pain for 3 months duration. Simultaneously he had urinary hesitancy, a feeling of incomplete voiding of urine along with sense of inadequate evacuation of stool. Fifteen days later he developed descending paresthesia from the upper abdomen up to the both feet followed by weakness of trunk muscles, weakness and tightness of both lower limbs over a period of 2 months, which initially started in left lower limb and subsequently involved the right lower limb. There was no loss of perianal sensation. On examination, his higher mental functions and cranial nerves were normal. His upper limb power was 5 on both sides with normal tone and deep tendon reflexes. His lower limb power was 3 with hypertonia, exaggerated reflexes and ill-sustained clonus on the both side. He had sensory impairment below T5 corresponding to vertebral level D3. General physical examination and other system examinations were normal. A provisional diagnosis of thoracic myelopathy was made and patient was investigated. His complete blood count, renal profile, liver function tests, human immunodeficiency virus (HIV) and hepatitis B surface antigen were negative. His chest X-ray was normal. Erythrocyte sedimentation rate was moderately high and Mantoux was nonreactive. Magnetic resonance imaging (MRI) of whole cord revealed an iso- to hypointense lesion at D3 level on T1-weighted imaging (T1WI). The lesion was iso- to subtle hyperintense with central flow void onT2-weighted imaging (T2WI) [Figure 1], with cord edema rostral to the mass. Contrast-enhanced MRI showed a brilliantly enhancing lesion with hypointense centre at D3 with sharp margins [Figure 2]. The oval-shaped lesion measured 16 x 10 mm. The diagnosis was intramedullary spinal cord tumor by MRI. Because of worsening of the patient's neurological examination, surgical removal of the lesion was undertaken. At D3-4, laminectomy was performed, posterior longidutinal myelotomy was executed, and a well-circumscribed pinkish fleshy mass [Figure 3] was found to be located 2 mm anterior to posterior aspect of the cord. The lesion was dissected along a readily definable plane and was removed totally by use of the operating microscope. The histopathology showed multiple granulomas [Figure 4] comprising of lymphocytes plasma cells, neutrophils, and large number of epitheloid cells [Figure 5]in clusters with demonstration of acid fast bacilli (AFB) [Figure 6] typical of Mycobacterium tuberculosis. Postoperatively the patient was given antituberculus treatment (ATT), started with isoniazid (INH) 300 mg/day, rifampicin (RF) 450 mg/day, pyrazinamide 1500 mg/day, and ethambutol 800 mg/day daily for 2 months, followed by INH and RF for 10 months. Pyridoxine at 40 mg/day was given for all 10 months. Postoperatively, the patient's neurological examination gradually improved and he could sit erect on the bed and able to walk over a period of 3 weeks without support. The follow-up time is 1 1/2 year. | intramedullary, spinal cord tumor, tuberculomas | Not supported with pagination yet | null |
PMC9667942_01 | Female | 61 | A 61-year-old Chinese woman presented with weakness and loss of appetite for the previous 20 days. She had a medical history of cholecystitis and underwent a cholecystectomy several years ago. Physical examination showed that the patient had a temperature of 36.7 C, blood pressure of 128/76 mmHg, and a heart rate of 77 beats/min. There were coarse breath sounds in both lungs and diminished breath sounds in both lower lungs; a small number of wet rales could be heard, and diminished heart sounds with enlarged heart borders due to pericardial effusion.
The electrocardiogram (Figure 1) suggested a sinus heart rate with low voltage in the limb leads. The patient's laboratory data at admission are shown in Table 1. Echocardiography indicated moderate to severe pericardial effusion (Figure 2), and echo-free areas were seen in the pericardial cavity. The diastolic fluid width was measured as 14 mm in the anterior wall of the right ventricle, 16 mm in the posterior wall of the left ventricle, 19 mm in the lateral wall of the left ventricle, and 20 mm in the apical part of the left ventricle. A bedside color doppler ultrasound showed bilateral pleural effusions. After admission, the patient had a fever intermittently, with a temperature of up to 38.3 C without chills and shivering. The patient's temperature was elevated within 24 h of admission, meaning that the possibility of community-acquired pneumonia could not be excluded. After blood cultures were retained, the patient was also given empirical anti-infective treatment with moxifloxacin. However, as the patient's improvement in relevant tests was considered not to exclude tuberculosis, the use of fluoroquinolones alone should be avoided, and the patient's moxifloxacin was discontinued and changed to ampicillin. The patient's blood culture later indicated no bacterial growth. A computed tomography (CT) scan of the lungs revealed sporadic inflammation in both lungs, inflammatory nodules in the upper left and lower right lung lobes, calcification in the upper left lobe (Figure 3), and bilateral pleural effusions. Furthermore, the mediastinal lymph nodes were enlarged and partially calcified. Pericardiocentesis and drainage were used to relieve the patient's symptoms, such as chest tightness and shortness of breath. The patient's pericardial effusion was hematogenous, with routine results as follows: protein 53.96 g/L; Reye's test positive; total erythrocyte count 214300.00 x 106/L; total leukocyte count 3762.00 x 106/L; percentage of single nucleated cells 84%; adenosine deaminase (ADA) 32.0 U/L; lactate dehydrogenase (LDH) 326 U/L; and carcinoembryonic antigen (CEA) 0.47 ng/ml.
The above results indicated that the patient's pericardial effusion was exudate. The pericardial effusion smear did not find acid-fast bacilli, and Xpert MTB/RIF (Xpert Mycobacterium TB/RIF test is a new test, which is helpful for rapid diagnosis of TB and drug resistance, thus bringing revolutionary changes to TB control.) and T-SPOT tests (The T-SPOT test is a unique TB blood test designed to reduce variability and maximize sensitivity, even in people with low immune function.) were negative. The exfoliated cells of the pericardial effusion showed lymphocytes and lobulated nuclei, and no cancer cells were found. Female tumor markers such as CEA, cancer antigen (CA) 125, CA 199, and neuron-specific enolase were below the reference values to exclude tumor-derived pericardial effusion. Further positron emission tomography/computed tomography (PET/CT) was performed, which showed inhomogeneous thickening of the pericardium, enhanced metabolism, mediastinal lymph nodes, and uterine metabolism fibroids. Therefore, we could almost exclude the possibility that pericardial effusion was caused by a tumor. The patient's thyroid function test suggested that her free triiodothyronine (FT3) of 2.31 pmol/L was only mildly depressed, and it was unlikely that the pericardial effusion was caused by hypothyroidism. To rule out the possibility that the patient's pericardial effusion was caused by autoimmune disease, we further performed autoimmune marker screening, and the patient's antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), and antiphospholipid. The antiphospholipid syndrome antibodies were all negative, which essentially excluded autoimmune diseases.
Three days after admission, the patient had no fluid flow from the pericardial drainage tube, so the pericardial drainage tube was removed. Seven days after admission, the patient's bedside color doppler ultrasound showed that the right pleural effusion was less than at the time of admission. However, there was still a considerable amount of pleural effusion on the left side. We gave the patient left-sided thoracic puncture drainage, and the drainage fluid was light-red. Routine examination of the pleural fluid showed protein 42.83 g/L; a positive Reye's test; total red blood cell count of 67,500.00 x 106/L; total white blood cell count of 1359.00 x 106/L; and percentage of single nucleated cells 97%. Its property was approximately the same as that of pericardial effusion, which was an exudate and the possibility of extravasation of a large amount of pericardial effusion could not be excluded. After receiving symptomatic supportive treatment, the patient's symptoms showed improvement, and the family refused to undertake further specific investigations to determine the cause.
However, 2 months later, the patient was readmitted with malaise, chest pain, and low-grade fever. She had been treated with cephalosporin at a local hospital before admission, but the outcome was poor. A small amount of pericardial effusion was again detected by echocardiography at the time of admission. To determine the cause of the pericardial effusion, the patient was referred to the department of thoracic surgery for a biopsy of the pericardial mass. Pathological findings showed granulomatous lesions and fibrous hyperplasia of the mediastinal lymph nodes (Figure 4) and granulomatous lesions of the pericardial fibrofatty tissue (Figure 5). Furthermore, the patient's pulmonary CT indicated a nodular calcified shadow in the left upper lung and enlarged and partially calcified lymph nodes in the mediastinum and part of the bilateral hilum. The patient was considered to have stable tuberculosis in the upper lobe of the left lung, and the pericardial puncture fluid was exudate with increased leukocytes, mainly monocytes, and mildly elevated ADA. TBP can be suspected according to the diagnostic criteria, and the patient was advised to go to an infectious disease hospital for further treatment. The dosing regimen was: isoniazid 300 mg orally one time a day (QD), rifampicin 600 mg orally QD, ethambutol 100 mg orally QD, and pyrazinamide 100 mg orally QD. The four drugs were administered for 8 weeks and then reduced to isoniazid and rifampicin to continue the treatment for 6 months. According to the PET-CT results, the patient's pericardium had become unevenly thickened. To avoid progression to constrictive pericarditis, the patient was given prednisolone 50 mg, and the dose was gradually reduced. After 8 months, we followed up with the patient by telephone; her symptoms, such as weakness and chest pain, were improved following the anti-tuberculosis treatment. | case, diagnosis, pericardial effusion (pe), review, tuberculosis, tuberculous pericarditis (tbp) | Not supported with pagination yet | null |
PMC7401980_01 | Male | 65 | Our patient was a 65-year-old man who had ultra-low anterior resection and chemo-radiotherapy for rectal cancer. On follow-up computed tomography (CT) scan of the abdomen and pelvis a year later, he was found to have a bladder mass (Fig. 1). He subsequently underwent elective TURBT and received intravesical mitomycin C (40 mg diluted in 40 ml of saline 0.9%) within 6 h post-operatively. Histology revealed non-invasive, low-grade TCC. Three weeks later, a follow-up CT scan of the abdomen and pelvis was performed for routine follow-up of the rectal cancer; this scan incidentally detected calcification of the bladder wall at the surgical resection site (Fig. 1). He was asymptomatic. Cystoscopy and cystolitholapaxy was then performed for presumed bladder calculi, approximately three months after the TURBT. Extensive stone-like, whitish calcification of the bladder wall at the surgical resection site was found (Fig. 2), not merely slough or soft tissue material. These lesions were further resected down to the detrusor muscle layer as the material was not amenable to washout. Histology (Fig. 3) revealed chronic inflammation of urothelium and fragments of refractile, hard-edged material which was found to be made up of calcium phosphate. There were no features of malignancy. He had normal serum calcium and phosphate levels and no known history of exposure to tuberculosis or schistosomiasis or travel to Africa, Middle East or South East Asia. He had no symptoms of interstitial cystitis. Aside from the history of rectal cancer and associated therapy, he had no other relevant oncological history. He received intravenous fluorouracil, folinic acid and oxaliplatin adjuvant chemotherapy for rectal cancer with the final cycle administered more than 12 months prior to this diagnosis of bladder wall calcification. He never received any intravesical therapy prior to the single dose of mitomycin C administered after the initial TURBT. In view of the rapid onset and localized involvement of the resection site, the bladder wall calcification was most likely secondary to intravesical mitomycin C treatment. Since this episode, there was no further recurrence or long-term consequence. Thus, no further treatment was required aside from routine cystoscopy for follow-up of non-muscle invasive, low-grade bladder cancer. | bladder cancer, mitomycin, side effects | Not supported with pagination yet | null |
PMC3438862_01 | Male | 16 | A 16-year-old right-hand-dominant high school quarterback sustained injury to the left shoulder while attempting to score a touchdown. The left upper extremity was outstretched overhead, with the ball, as the patient dove into the end zone. As the patient landed, he was tackled from behind by another player, with direct contact to the posterior aspect of the left shoulder. The patient had immediate severe pain in the left shoulder and was unable to continue play. He was evaluated locally the following day owing to continued pain and inability to elevate the upper extremity. Radiographs revealed posterior humeral subluxation but no fracture. An magnetic resonance imaging (MRI) scan was ordered, and he was referred to our institution for further evaluation and management.
Our initial evaluation, 4 days postinjury, revealed a guarded posture and diffuse tenderness throughout the shoulder. Although passive range of motion was unrestricted (though with significant discomfort), the patient displayed limited active range of motion of the shoulder. Rotator cuff strength testing revealed 2/5 strength on shoulder abduction (supraspinatus) and external rotation (infraspinatus) with a positive liftoff test (subscapularis). Instability evaluation was limited, secondary to patient discomfort and guarding; however, no discrete anterior instability was documented with load and shift or with abduction and external rotation. The humeral head was resting posterior but in a reduced position. Increased translation and pain were present with a posterior load and shift, but the shoulder was not able to be dislocated. Sulcus sign was negative. The patient was neurovascularly intact.
The MRI revealed marked posterior subluxation of the humeral head with a large accumulation of edema and hemorrhage in the glenohumeral joint. The MRI also revealed complete, full-thickness tears of the supraspinatus and infraspinatus tendons from their insertions; a complete, full-thickness tear of the subscapularis with medial subluxation of the long head of the biceps tendon; and a probable full-thickness tear of the teres minor tendon (Figure 1).
The patient was subsequently taken to the operating room 7 days postinjury. Given the 4-tendon involvement, an open-cuff repair was planned; however, arthroscopy was recommended to first assess the labrum and biceps tendon. An arthroscopic evaluation was therefore performed and so demonstrated the marked hemorrhage and edema in the glenohumeral joint (Figure 2). The extensive injury to the rotator cuff was confirmed, as was instability of the biceps tendon. Remarkably, the glenoid labrum was found to be intact throughout its perimeter with no posterior labral disruption. A debridement of the tendon edges and hemorrhage was completed, the biceps released, and the arthroscope removed in preparation for the open approach. The arthroscopic portion of the case was kept brief to prevent excessive swelling from hampering the open repair.
A combined anterior and posterior approach was selected owing to concern that a single extended approach may not allow complete access to the extremes of the rotator cuff for repair. The posterior approach was first performed. A longitudinal incision was created overlying the deltoid and centered on the posterior glenohumeral joint. The posterior arthroscopic portal was incorporated into the incision. The deltoid fascia was incised, and upon splitting the deltoid fibers, the posterior humeral articular surface was in direct visualization, confirming a complete avulsion of the infraspinatus tendon and disruption of the posterior capsule (Figure 3). Involvement of the teres minor was also documented. Two bioabsorbable anchors with a total of 4 suture sets passed in horizontal mattress configuration were used to accomplish a repair of the infraspinatus and upper teres minor tendons.
A deltopectoral approach was then performed. Upon development of the interval, it was readily evident that the subscapularis tendon had completely avulsed off of its insertion onto the lesser tuberosity and the biceps tendon had subluxed medially out of the bicipital groove. During superior retraction, access to the supraspinatus was achieved and the full-thickness tear was easily identified. A total of 3 additional double-loaded bioabsorbable anchors were placed to repair the supraspinatus and subscapularis. With each anchor, both sets of sutures were passed in horizontal mattress configuration. In all, 5 anchors and 10 suture sets were used to complete the rotator cuff repair. The excellent tendon quality and mobility and strong repair resulted in confidence with a single-row repair. A second row was not deemed to be necessary. A biceps tenodesis was also performed through the anterior approach with the use of a bioabsorbable tenodesis screw. All wounds were thoroughly irrigated and closed. The patient was placed into an external rotation sling with the arm in neutral.
At 2-week follow-up, sutures were removed and the patient was continued in the external rotation sling. Elbow range of motion and pendulum exercises were initiated. At 4-week follow-up, radiographs revealed a concentric reduction of the glenohumeral joint. Physical therapy was initiated for passive range of motion. At 8-week follow-up, the patient continued to show improvement but reported involvement in a motor vehicle accident 2 weeks beforehand (6 weeks following surgery) with transient increase in shoulder pain. Range of motion revealed forward flexion to 120 and external rotation to 20 . Due to the recent trauma, a repeat MRI was ordered. The MRI, eventually performed nearly 3 months postsurgery, revealed a concentrically reduced glenohumeral joint with no evidence of persistent or recurrent rotator cuff tear (Figure 4). Clinical follow-up at this time demonstrated continued improvements in motion with active forward flexion to 140 and external rotation comparable to the contralateral side at 60 . No instability was evident on clinical exam and the patient was without apprehension. At the last clinical follow-up, 5 months following surgery, the patient demonstrated 170 of active forward flexion and abduction, external and internal rotation comparable to the contralateral side, and an intact rotator cuff throughout to strength testing. At 6 months, the patient had returned to baseball with no recurrent symptoms, and 1 year following injury he has returned to football without complaint. | adolescent, athlete, rotator cuff tear | Not supported with pagination yet | null |
PMC9449415_01 | Male | 25 | A 1.25 year old, male-neutered Chihuahua was presented with a four-day history of lethargy, decreased appetite, and tachypnea. He was regularly dewormed and vaccinated. In the general examination, the dog showed mild apathy and generalized high-frequency, low-amplitude tremor. Rectal body temperature was 38.7 C. Breathing pattern was normal, frequency was 32/min with physiological effort. Auscultation was inconclusive due to whole body tremor. Coughing and retching was provoked when palpating the larynx. On cardiac auscultation the heartbeat was regular with 120 beats per minute (bpm), no heart murmur was audible. Femoral pulses bilaterally were strong, regular, and synchronous with heart beat. Capillary refill time was under 2 s, the mucous membranes were pale-pink and moist. Peripheral lymph nodes were non-painful, soft and under 1cm in diameter on palpation. Abdominal palpation revealed no abnormal intraabdominal structures and no signs of pain. Mild serous ocular discharge in both medial canthus was noted without any other ocular abnormalities. Macroscopical evaluation of external ears, nose, and skin were unremarkable. Gait and posture were normal. At this timepoint, a neurological examination was not performed due to the lack of obvious involvement of the nervous system on general examination. Complete blood count, clinical chemistry, serum electrolytes, and abdominal ultrasonography were without clinically relevant abnormalities. The owner declined thoracic radiographs at this time point and decided for further outpatient therapy with non-steroidal anti-inflammatory and antibiotic medication. At home, 12 h after first presentation in the clinic, the dog developed generalized tonic-clonic seizure. The seizure had lasted for more than 2 h before the dog was presented to the emergency service again. The dog showed tonic-clonic movements, impaired consciousness, salivation, and a gurgling laryngeal stridor during in- and expiration. Body temperature was measured at 42 C, the heart rate was 162 bpm, no heart murmur was audible. Femoral pulses were strong bilaterally, regular, and synchronous with the heartbeat. Breathing frequency was 52/min. Capillary refill time was under 2 s, the mucous membranes were pale-pink and moist. The dog had brown-reddish diarrhea. Neurologic examination revealed generalized tonic-clonic seizure while the dog was in lateral recumbency. Menace response was absent in both eyes. The dog showed no facial paralysis and an increased tone of the masticatory muscles. Pupillary light reflex, gagging, strabismus, vestibulooccular reflexes, facial sensation, pain sensation and spinal reflexes were not evaluable due to ongoing seizure. The dog was stabilized with diazepam (4 x 2 mg/kg i.v., Diazepam Lipuro, B.Braun, Melsung, Germany) and phenobarbital (2 x 2 mg/kg i.v., Luminal, Desitin, Hamburg, Germany) and resuscitative fluid therapy (20 ml/kg/h for 3 x 20 min as bolus infusion, Sterofundin ISO Vetcare, B.Braun, Melsung, Germany) followed by continuous rate infusion (3 ml/kg/h, Sterofundin BG-5, B.Braun, Melsung, Germany). Thoracic radiographs were unremarkable. After cardiovascular stabilization and treatment of seizures leading to their interruption, neurological examination showed coma, bilateral non-responsive miotic pupils, and generalized absent cranial reflexes, while the breathing pattern remained normal, why a severe brainstem lesion with primary forebrain disease was suspected. Due to a grave prognosis, the owners elected for euthanasia.
Post mortem MRI (Figure 1) showed generalized swelling of the gray matter in the cerebrum and cerebellum with secondary flattening of gyri and sulci. Cortical gray matter displayed increased signal in T2w and FLAIR and decreased signal in T1w. The boundary between subcortical white matter and cortical gray matter was mostly blurry in all sequences. Caudal brainstem and cerebellum showed multifocal, intraaxial, small, round lesions with signal void in T2w and T1w. The fourth ventricle and cisterna magna were filled with material causing signal void in T2w and T1w without significant mass effect.
Examination of CSF sampled post mortem atlanto-occipitally revealed severely elevated number of erythrocytes without signs of erythrophagocytosis. Leukocyte value was elevated, the exact number was not countable. Protein content measured 188 mg/dl (reference values <25 mg/dl). Cell differentiation showed 91% lymphocytes, 7% monocytes and 2% neutrophils.
At necropsy, a moderate flattening of the gyri and narrowing of sulci of the brain (Figure 2A) was observed in conformity with the MRI results and interpreted as edema. In addition, mild cerebellar vermal herniation into the foramen occipitale magnum was visible. The meningeal vessels were moderately and diffusely congested. The dog had hemorrhagic intestinal content and a single nematode was found in the small intestine. Histopathologicallly, the gray matter of the cerebrum as well as the cerebellum showed moderate, multifocal, non-symmetrical, lympho-plasma-histiocytic, necrotizing inflammation. Inflammatory cell infiltrates were mainly found in the perivascular space. Furthermore, primarily small to medium sized blood vessels in the gray matter and especially prominent in the leptomeninx displayed loss of integrity of the vascular wall with moderate to severe infiltration with partially degenerated lymphocytes and macrophages resembling vasculitis of the leukocytoclastic type (Figure 2B). The spinal cord did not show any morphological changes.
IHC of selected sections of the CNS revealed infiltration of a moderate to high number of CD3-positive T-lymphocytes, low to moderate number of CD204-positive macrophages and few CD20-positive B-lymphocytes, respectively, in the partially destructed vascular wall and the perivascular space (Figures 2C-E). Using IHC and histochemistry, no infectious agent or signs of demyelination were detected.
In addition, mild, mucosal hemorrhages and few dilated crypts and mild flattening of villi were observed in the small intestine. Due to the macroscopic and histological lesion in the small intestine, parvovirus infection was ruled out by IHC. The spleen showed moderate lymphoid depletion. In the lung only moderate, diffuse, acute alveolar edema and hyperemia were found. These changes were interpreted as having developed during agony. No signs of parasites, e.g. Angiostrongylus vasorum, were found in the lungs, heart, gastrointestinal tract, or CNS via gross and microscopic examination. The remaining investigated tissues lacked significant microscopic lesions. | brain, canine (dog), central nervous system (cns), inflammation, meningoencephalitis of unknown origin (muo), sterile | Not supported with pagination yet | null |
PMC9449415_02 | Unknown | 10 | A 10 year old, male-neutered, medium sized, mixed breed dog was presented with a one-week history of progressive neurological signs. Initially, the dog was dull and showed a low head carriage. Clinical signs progressed to pacing in circles to the right, dysphoria, and suspected right sided visual deficits. There was no travel history. The dog was regularly vaccinated and dewormed.
The dog was presented in lateral recumbency. The dog was stuporous. Rectal body temperature was 38.2 C. Breathing pattern was normal, frequency was 34/min with physiological effort. Auscultation revealed mildly increased vesicular sounds, which were interpreted as still within physiological limits. On cardiac auscultation the heartbeat was regular with 90 bpm, no heart murmur was audible. Femoral pulses were strong, regular, and synchronous with heartbeat. Capillary refill time was under 2 s, the mucous membranes were pale-pink and mildly sticky on palpation. Macroscopical evaluation of eyes, external ears, nose, and skin were unremarkable.
The owner declined any further diagnostic attempt or therapy. After 3 h in the clinic, the dog suffered spontaneous cardio-respiratory arrest and died.
Macroscopically, an approximately 4 cm in diameter sized accumulation of coagulated blood was found within the lateral ventricle of the left hemisphere of the brain (Figure 3A). The adjacent brain parenchyma showed multifocal hemorrhages. Other findings comprised mild endocardiosis of the atrioventricular valve as well as multiple nodular masses within the spleen. Histopathologically, focal, severe hemorrhage corresponding to the macroscopic finding was visible in the left lateral ventricle and the neighboring brain parenchyma. Furthermore, moderate to severe, lympho-histiocytic infiltrates were detected within the meninges and brain parenchyma, and associated with non-leukocytoclastic vasculitis, most frequently in the cerebral cortex, hippocampus, brain stem, and cerebellum (Figure 3B). Furthermore, similar, but mild inflammatory changes of leptomeningeal blood vessels were found in the cervical, thoracic, and lumbar spinal cord. Additionally, within the perineural tissue of the optic nerve of the left eye mild, lympho-histiocytic vasculitis was detected as well as a mild cataract. In between nerve fibers of the trigeminal nerve, moderate, focal, acute hemorrhage was found. Using IHC, perivascular infiltrates in the CNS comprised equal numbers of CD3- and CD20-positive lymphocytes and multifocal, irregular infiltration with few CD204-positive macrophages. Using IHC and histochemistry, no infectious agent or signs of demyelination were detected.
Further alterations of minor significance comprised mild, follicular hyperplasia in the tonsils and mild, multifocal anthracosis in the lung as well as mild, acute, diffuse, alveolar edema. The splenic nodules were diagnosed as nodular hyperplasia. No signs of parasites, e.g. Angiostrongylus vasorum, were found in the lungs, heart, gastrointestinal tract, or CNS via gross and macroscopic examination. | brain, canine (dog), central nervous system (cns), inflammation, meningoencephalitis of unknown origin (muo), sterile | Not supported with pagination yet | null |
PMC9449415_03 | Male | 75 | A 10.75 years old, male-neutered Australian Shepherd with a 2-day history of progressive gait abnormality and two self-limiting generalized tonic-clonic seizures was presented. Two months before presentation, the dog showed a left sided facial paralysis, which completely resolved after 15 days of prednisolone treatment by the primary veterinarian. The vaccination status was not reported.
At the time of presentation, the dog showed orofacial seizures, which developed into generalized tonic-clonic seizures and could be controlled with diazepam (2 mg/kg i.v.). Rectal body temperature was 39.4 C. Heartbeat was 90 bpm without murmur on auscultation. Breathing pattern was normal, frequency was 40/min with physiological effort. Auscultation revealed mild vesicular lung sounds. Capillary refill time was under 2 s, the mucous membranes were pink and moist. Abdominal palpation was within normal limits. Macroscopical evaluation of eyes, external ears, nose, and skin were unremarkable. Blood examination revealed mildly elevated alanine aminotransferase (102 U/l; reference <50 U/l) and alkaline phosphatase (193 U/l; reference >150 U/l) activity. Clinical signs progressed within 24 hours, and the dog showed severe bradypnea and cyanosis. At neurological examination the dog was in lateral recumbency with generalized increased muscle tone and high-frequency, low-amplitude generalized tremor. He was comatose, showed bilateral absent palpebral reflexes and menace response and decreased pupillary light response on both eyes. Vestibuloocular and spinal reflexes were not tested. Consequently, the dog was intubated and mechanically ventilated.
Subsequent MRI (Figure 4) showed generalized flattened sulci and reduced volume of internal and external CSF space due to swelling of the CNS parenchyma. The FLAIR sequence revealed a subtle, diffuse, increased signal intensity of the internal capsule. There was transtentorial forebrain herniation as well as caudal foraminal herniation of the cerebellum with severe compression of the brainstem. At the site of compression, there was an intraaxial, T2w hyperintense lesion with multifocal signal void in the brainstem. There was no physiological contrast enhancement in the choroid plexus, which was suspected to be secondary to the compressed basilar artery preventing contrast agent to reach the CNS parenchyma.
Due to an infaust prognosis, no further examinations were performed and the dog was euthanized on owner's request.
Necropsy revealed a generalized swelling of the brain with mild herniation of the cerebellar vermis into the foramen occipitale magnum as well as herniation of the occipital lobe underneath the tentorium cerebelli osseum as indicated in the MRI. Furthermore, there was severe, acute hemorrhage and softening of the neuroparenchyma within the brain stem (Figure 5A).
Histologically, the cerebral cortex, cerebellum, brain stem as well as the spinal cord showed severe, lympho-histiocytic and plasmacytic panencephalomyelitis and meningitis with perivascular edema (Figure 5B). Additionally, severe vasculitis with inflammatory infiltrates in the damaged vascular wall (leukocytoclastic vasculitis) and in the perivascular space was found within the brain and the spinal cord, accompanied by moderate to severe hemorrhage. Spinal ganglia displayed mild to moderate infiltration of lymphocytes and macrophages, too. Additionally, the right eye displayed a mild to moderate, lympho-histiocytic to granulomatous neuritis and perineuritis of the optic nerve.
IHC of the CNS (Figures 5C-E) revealed that the majority of inflammatory cells infiltrating the vascular wall as well as the perivascular space were comprised of B- and T-lymphocytes. B-lymphocytes outnumbered T-lymphocytes in most of the investigated areas. Few infiltrating cells represented CD204-positive macrophages in these regions. However, the number of infiltrating macrophages was variably increased in other areas, where less lymphocytes were visible.
Using IHC and histochemistry, no infectious agent or signs of demyelination were detected.
Additionally, the tracheobronchial lymph node showed severe anthracosis. The bone marrow revealed a dominating myeloid cell population. In lungs, heart, gastrointestinal tract, and CNS no parasites were found. | brain, canine (dog), central nervous system (cns), inflammation, meningoencephalitis of unknown origin (muo), sterile | Not supported with pagination yet | null |
PMC1079876_01 | Female | 28 | A 28-year-old postdoctoral researcher experienced multiple episodes of vomiting from the age of 3 years. The episodes occurred with upper respiratory tract infections and asthma, and generally lasted 24-48 hours. The patient's mother had nearly identical episodes during childhood. The maternal grandmother experienced hyperemesis gravidarum. The patient's sister and paternal grandfather had classical migraine headaches.
The patient first presented to the hospital at age 10 1/2 years. A typical vomiting attack had been triggered by a cold, but had not resolved after four days. Despite treatment with intravenous fluids, the vomiting continued for a further two days before resolving. Cyclical vomiting was diagnosed. She was subsequently hospitalised repeatedly with episodes of about four days duration, with vomiting occurring every 5 to 10 minutes at peak. She continued to have similar attacks during every infection, but never without prior infection. The symptoms were refractory to anti-emetics available at the time (eg. metoclopramide, prochlorperazine).
Shortly before Christmas of that year (1986), a 6 1/2-day vomiting episode was triggered by pneumonia, and the patient spent the Christmas period in hospital. The following year (1987), a cold triggered a CVS attack two days before Christmas. Having spent two successive Christmases in hospital, the patient hoped to be well the next year. However, she was woken by nausea in the early hours of Christmas Day 1988 and began vomiting. Uniquely, this episode had not been triggered by an infection, and the patient (then aged thirteen) recognised this. Subsequently, episodes rapidly increased in frequency: compared with an average of 7.3 episodes per year in the three preceding years, the patient averaged 22.3 episodes per year over the three years following Christmas 1988. Many further episodes now occurred without infection, but coincided with visits to certain places (e.g. friend's house), or commenced on specific days of the week (e.g. Saturday). Most episodes resulted in 3-8 day hospitalisations. At one point, a repetitive cycle commenced, where each episode occurred exactly two days after discharge from hospital following the previous attack. The patient was aware of this pattern and consciously afraid of becoming ill at the expected time. Her attacks always commenced nocturnally and she became reluctant to go to sleep, fearful of another episode beginning.
The patient experienced exhaustion and severe, intractable nausea for the entire length of her emetic episodes (up to 6 1/2 days), and the nausea caused marked behavioural changes. Sleep was the only state that allowed her to be insensible to nausea, but she was often unable to lie down, as this intensified her nausea, causing retching and heartburn. Instead, she spent hours sitting motionless in bed with her hips and knees flexed, her arms and head resting on her knees and her eyes closed. She was unable to lie supine for abdominal palpation. She would repeatedly expectorate, as she experienced hypersalivation and was too nauseated to swallow. Accumulated oral secretions, and the profound fatigue and confusion that accompany nausea, contributed to her verbal unresponsiveness. Attempting to reduce intolerable nausea, she frequently induced vomiting by drinking large volumes of water. This also diluted bile and gastric acid, thus lessening oesophageal and oropharyngeal discomfort during vomiting.
Consistent with the natural history of the condition, the attacks gradually became less frequent as the patient grew older. Availability of newer anti-emetic agents (5-HT3 antagonists) also contributed to the improvement: prompt treatment of episodes with intravenous ondansetron, ranitidine and analgesics reduced the duration and severity of attacks, and the same medications were partially successful as prophylactics. Thus, having achieved partial symptom control, and an understanding of how her anticipation of episodes was exacerbating her condition (and therefore when to use prophylactic medication), the patient felt more in control of her illness, feared it less, and conditioned responses to situations previously associated with CVS attacks gradually diminished. To date, the patient has been hospitalised nearly 100 times, however now experiences vomiting attacks only rarely (fifteen episodes over the past decade, including only one episode over the past five years). | null | Not supported with pagination yet | null |
PMC5703761_01 | Female | 50 | A 50-year-old woman with a history of uncomplicated Crohn's disease presented for esophagogastroduodenoscopy (EGD) for evaluation of acute epigastric pain, nausea, and bilious vomiting. EGD revealed retained food in the stomach and what appeared to be a large, approximately 2-cm obstructing gallstone in the duodenal bulb (Figure 1). After multiple instruments failed to retrieve the gallstone, a needle knife was utilized to break the gallstone into pieces that were then retrieved using a Roth net. After removal of the gallstone, a suspected cholecystoduodenal fistula was seen. An emergent computed tomography of the abdomen confirmed a fistulous tract between the gallbladder and duodenum (Figure 2). Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated contrast extravasating from the gallbladder into the duodenum. Biliary sphincterotomy was performed with the placement of a 10 Fr x 5 cm plastic biliary stent in the common bile duct. An additional stone that was impacted within the cholecystoduodenal fistula was removed successfully using a stone-extracting balloon (Figure 3). An endoscopic suturing device was utilized to place one endoscopic suture, resulting in complete closure of the fistula (Figure 4). The patient subsequently underwent uncomplicated, open cholecystectomy with no fistula seen during surgery.
Compared to gallstone ileus, which causes obstruction near the terminal ileum, Bouveret syndrome is a rare presentation of gastric outlet obstruction occurring proximally at the duodenal bulb. Diagnosis is based on the clinical manifestations, existence of pneumobilia on imaging, visualization of lithiasis, and demonstration of duodenal obstruction. Treatment has traditionally been surgical with enterolithotomy, usually by laparotomy or laparoscopy; closure of the fistula; and finally cholecystectomy. Many cases of successful endoscopic management for Bouveret syndrome have been described involving removal of the gallstone, mechanical lithotripsy, electrohydraulic lithotripsy, extracorporeal shockwave lithotripsy, and duodenal stenting. Our case demonstrates the successful endoscopic retrieval of the obstructing gallstone and the use of a biliary stent to reduce pressure in the cholecystoduodenal fistulous tract. Furthermore, we show a unique approach to cholecystoduodenal fistula closure using an endoscopic suturing device. Endoscopic suturing devices have been available for more than a decade now and have been used for perforation closure, stent fixation, fistula closure from surgical complications, peroral endoscopic myotomy mucosotomy closure, postbariatric surgery endoscopic stoma reduction, and primary endoscopic obesity surgery. | null | Not supported with pagination yet | null |
PMC4712211_01 | Female | 60 | A retired 60 year-old Caucasian female with SLE was admitted to the Rheumatology Department in our hospital with persistent low-grade fever, night sweats, malaise, weakness and weight loss. She had no neurologic, respiratory, gastrointestinal or urinary symptoms, and no cutaneous lesions or joint pain, although she had a sensation of abdominal fullness. The symptoms had started approximately one year earlier, had shown progressive worsening, and she had lost 30 kg (approximately 1/3 of her previous body weight). During that time she was seen by her primary care physician (PCP) on several occasions and had several consultations with her rheumatologist. The investigation performed had been negative for common pathogens associated with chronic febrile illnesses, such as tuberculosis and brucellosis, and progression of immunosuppression had not stalled the symptoms. The patient had been treated for presumptive tuberculosis for 6 months, having shown no signs of improvement.
The patient had been diagnosed with SLE in her late 20s, had consultations with a rheumatologist in our hospital since 2003, and was being treated with a daily dose of 5 mg prednisolone and a weekly 10 mg dose of methotrexate. She also had diabetes mellitus and hypertension, both being treated by her PCP. Her SLE had been deemed controlled until these symptoms started, and she had no past history of confirmed tuberculosis or any chronic febrile infection. An HIV screening performed by her PCP had been negative. She had no past surgeries and no family history of cancer. The patient lived in a farm, in a town located in the region of the Douro river basin, in the north of the country. She had no history of smoking or of any drug use.
On admission, the only abnormalities were a low-grade fever (37.5 C), marked pallor and a palpable, non-tender hepatosplenomegaly. Her blood pressure was 105/63 mmHg, heart and respiratory rates were 84/min and 18/min, respectively. There were no abnormalities on cardiac or lung auscultation, no rash, and her neurologic examination was unremarkable. A careful examination revealed no swelling, redness or pain of any joint.
Preliminary analytical study revealed pancytopenia, with a hemoglobin of 8.0 g/dL, white blood cell count (WBC) of 3020/mm3, and platelet count of 98,000/mm3, erythrocyte sedimentation rate (ESR) of 116 mm/h, lactic dehydrogenase (LDH) of 2331 U/L, low serum albumin (18 g/L) with increased total proteins (90 g/L). Hepatic aminotransferases were slightly elevated, bilirubin, blood urea nitrogen and creatinine were normal. Blood was also collected for culture of bacteria, mycobacteria and fungi, and for serologic study. Chest X-ray showed no opacities, nodules or effusions; abdominal ultrasound revealed massive hepatosplenomegaly, with a liver and spleen of 35 cm and 16 cm, respectively. The first diagnostic hypothesis was a hematologic malignancy, although subacute infections such as brucellosis or tuberculosis were also considered. A differential protein analysis with electrophoresis, antibody search, and full body computerized tomography (CT) scan were performed. A Hematology consultation was requested.
The patient had marked hypergammaglobulinemia, with a total gamma globulin count of 7580 mg/L, and a polyclonal gamma curve was seen on electrophoresis; gamma globulin differential was normal. There was no complement consumption, anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA), and anti-double stranded DNA (anti-dsDNA) antibodies were negative. Full-body CT confirmed the hepatomegaly and homogeneous splenomegaly, but did not show any other relevant abnormalities. Serial blood cultures for bacteria, mycobacteria and fungi were persistently negative. The serologic study revealed multiple positive IgG and IgM for Coxiella burnetti, Mycoplasma pneumoniae and for Rickettsia conorii. IgM for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B-19 were negative. Blood and bone marrow cultures for bacteria and fungi were negative. Bone marrow aspirate and biopsy were performed and sent for histologic and microbiologic study (culture for bacteria and mycobacteria). The patient and the preliminary results of the marrow smear were seen by an experienced hematologist who considered the patient had no consistent signs of hematologic malignancy. Amoxicillin/clavulanate and ciprofloxacin were empirically administered, but showed to be ineffective.
On day 18 of admission, an infectious diseases (ID) consultation was requested. The clinical history and the physical examination were those previously described, but the patient revealed for the first time that she lived next to livestock and that her husband was a sports hunter, had a pack of dogs, and one had died recently of an undiagnosed consumptive disease. The hypothesis of visceral leishmaniasis was considered: the patient had an appropriate background, prolonged fever and constitutional symptoms, pancytopenia, and increased protein count with low albumin and hypergammaglobulinemia. The multiple positive antibodies were interpreted as resulting from increased gamma globulin production. Polymerase chain reaction (PCR) for L. infantum was positive both in the blood and in the bone marrow.
The patient was transferred to the ID Department and was treated with liposomal amphotericin B (AmB), in a dosing of 3 mg/kg. She received one daily dose during the first 5 days, another one on day 10, and then once weekly until she completed 10 doses. A prolonged regimen was chosen due to her long standing immunosuppression, long duration of disease, and overall poor clinical condition. She was discharged on day 29 of admission (10 days after being transferred to the ID department), after completing her sixth dose of AmB. She showed great improvement, sustained normal body temperature once she started treatment, and recovered some of the analytical anomalies. The patient completed therapy in our department's ambulatory clinic. A histologic review of the bone marrow biopsy showed histiocytes infected with amastigotes, confirming our diagnosis, without any signs of primary hematologic disease.
Six months later, on her second appointment after discharge, the patient was completely asymptomatic, had recovered 10 kg, and had an overall normal physical examination. Hemoglobin rose to 11.7 g/dL, WBC to 7340/mm3, platelet count to 164,000/mm3, total serum protein was 81 g/L, serum albumin rose to 34 g/L and globulin count decreased to 5460 mg/L; abdominal ultrasound no longer showed signs of organ enlargement. | ana, anti-nuclear antibodies, amb, amphotericin b, cmv, cytomegalovirus, ct, computerized tomography, ebv, epstein–barr virus, ena, anti-extractable nuclear antigens, esr, erythrocyte sedimentation rate, fever, hiv, human immunodeficiency virus, id, infectious diseases, lab, liposomal amphotericin b, ldh, lactic dehydrogenase, pcp, primary care physician, pcr, polymerase chain reaction, rna, ribonucleic acid, sle, systemic lupus erythematosus, systemic lupus erythematosus, vl, visceral leishmaniasis, visceral leishmaniasis, wbc, white blood cell count, dsdna, double-stranded deoxyribonucleic acid | Not supported with pagination yet | null |
PMC10262133_01 | Male | 28 | A 28-year-old male patient known to have bronchial asthma and allergic rhinitis presented in February 2014 with complains of fever, productive cough, and shortness of breath for 2 weeks.
He was febrile, and his chest radiograph was showing lower, mid zone consolidation.
He was initially treated as a community-acquired pneumonia with antibiotics. His fever however did not subside, so he had further investigations including sputum culture and acid-fast bacilli smear were negative, and then bronchoscopy with bronchoalveolar lavage was done, turned to be positive acid-fast bacilli smear, and confirm rifampicin resistance, and later culture confirms the MDR-TB as the resistance including rifampicin, isoniazid, ethambutol, and streptomycin.
So, he was started on MDR-TB regimen which include six drugs: amikacin, moxifloxacin, pyrazinamide (PZA), cycloserine (cyclo), linezolid (Lzd), ethionamide (Eto).
However, he was able to continue this regimen for only 3 months, and then he developed severe lower limb sensory motor polyneuropathy. Unfortunately, he took only Eth, cyclo, and para-aminosalycilic acid (PAS) for another 10 months and then ethionamide and cycloserine (due to PAS-induced GI upset) for another 4 months, and after that, the patient chose to stop the treatment after total treatment period of 17 months.
Two months later, he started to complain of right shoulder pain, tenderness with right shoulder pain, and with limitation of movement for 4 months. MRI shoulder showed abscess-like lesion in the proximal humerus (Fig. 1). At this stage, he denied any respiratory symptoms, while his chest X-ray showed resolution of right lower lobe consolidation.
He got admitted for incision and drainage. The bone was found to express frank pus which was sent for TB-PCR which came also positive from the pus.
Biopsy specimen of the bone revealed necrotizing granulomatous inflammation and abscess formation (Fig. 2). After a discussion between the Infectious & respiratory teams which decided to resume second line anti TB and due to the high possibility being even of XDR-TB especially that quinolone sensitivity was not available.
Moreover, a decision was made to treat the patient with the initiation phase of treatment was given for 4 months (6 drugs: Mfx, Lzd, capreomycin, cyclo, PZA, Clr); he was instructed for good compliance.
He was able to be on this regimen only for 4 months as he developed again severe peripheral neuropathy in his lower limbs and hands despite using high dose of vitamin B6, i.e., pyridoxine (200 mg daily) plus symptomatic treatment with gabapentin and carbamazepine. So Capreomycin, Moxifloxacin & Linezolid were suspended then he was continued on {PZA, PAS,, Cyclo,Co-amoxiclav (Clav) & Bedaquiline (Bdq)} was started then continued for 1 year only because of shortage in cycloserine supply it was discontinued so he remain on {PZA, PAS, Bdq, Clav & Clarithromycin (Clr)} which is considered relatively weak regimen although the patient was advised to resume either linezolid or fluoroquinolone but he was reluctant because of neurotoxicity as well as no other options of second line anti TB regimen was available.
The last second-line regimen mainly depends on three drugs including PZA, PAS, and Bdq according to the recent WHO guidelines 2020 in addition to old two drugs which is Clr and Clav which is considered no longer recommended in prolong MDR-TB treatment, so he was continued on this regimen, but for longer duration guided by radiological imaging, he completed another 4 years with serial follow up of MRI humorous which showed dramatic response of the size of the osteomyelitis infection (Fig. 3).
In view of suboptimum continuation phase, so total treatment was extended to almost 5 years, and it was discontinued with follow-up MRI showing dramatic improvement after 14 months from stopping the treatment without any signs of recurrence. | osteomyelitis, pulmonary medicine, radiology, tuberculosis | Not supported with pagination yet | null |
PMC7751704_01 | Female | 20 | A 20-year-old woman fell while playing volleyball and incurred a subtrochanteric fracture of her right femur (Figure 1). The patient had the following typical imaging manifestations of OP: increased radiation density of the entire skeleton, absence of medullary canals, appearance of a "thick Jersey spine" or "sandwich vertebrae" caused by thickening of the vertebral endplates, and several sclerotic concentric bands (bone-within-bone) in the iliac wing (Figure 2A). Radiographs of the right knee showed no "Erlenmeyer flask" deformity of the distal femur (Figure 2B). She had no cranial and facial distortions or syndactylies of the fingers and toes, but she was short (145 cm). Laboratory examination results showed normal hematological parameters, thyroid hormone levels, and alkaline phosphatase concentration. There was no evidence of skeletal deformities, hepatosplenomegaly, or cranial nerve disturbances. The patient had no previous history of fractures, anemia, recurrent infections, or bone pain. The patient was diagnosed with ADO type II (known as Albert-Schonberg disease or marble bone disease). The X-ray examination results of her parents were normal, and they had no history of fractures. The family history of previous generations was unknown. The patient and her parents refused to undergo genetic examinations.
As access to the intramedullary canal may not have been possible in this patient, we chose to use a DHS instead of intramedullary nailing. The procedure was technically challenging. The patient was placed in the supine position on a fracture traction table under general anesthesia. The fracture was reduced under fluoroscopic visualization. New sharp drill bits were used, as blunt drill bits were more likely to break. Saline was continuously applied to help keep the drill bit cool to prevent bone necrosis and drill bit breakage. It took 30 minutes to create the hole and insert a guidewire for the lag screw. Reaming along the guidewire was also difficult and time-consuming. The sclerotic bone produced excessive resistance to tapping. During the tapping process, the surgeon felt a sudden cracking sensation through the handle. A femoral neck fracture was detected by fluoroscopy. The nondisplaced fracture was located in the middle of the femoral neck, and the lag screw provided adequate stable fixation and compression. Therefore, we decided to proceed with the original surgery plan. Subsequently, the lag and plate were attached (Figure 3A and B). During the surgery, a cortical screw and six drill bits were broken, and a few guidewires were bent.
The patient was instructed to carry out active hip and knee joint training from the first postoperative day and used crutches to walk without placing weight on the affected limb for 7 days postoperatively. The patient had obtained 90 active hip flexion at 3 weeks postoperatively. She was discharged on crutches and instructed not to bear weight on the affected limb until the fracture had healed. Routine postoperative clinical and radiological follow-up examinations were performed. At 12 months postoperatively, there was complete healing of the fractures on X-ray examination, and the patient was allowed to commence full weightbearing (Figure 4A and B). At 2 years postoperatively, the patient was pain-free with full range of motion of the hip and had returned to work. | autosomal dominant osteopetrosis, dynamic hip screw, osteopetrosis, subtrochanteric fracture | Not supported with pagination yet | null |
PMC8164334_01 | Female | 17 | A 17-year-old black African female initially presented to a local clinic with 2 weeks of gradual-onset bi-frontal headache, insomnia, and subjective fevers. She was treated for non-specific infection - despite no documented fever or microbial isolates - with empiric antibiotics for 10 days during which she also developed restlessness and third-person auditory hallucinations. She was then referred to a psychiatrist who diagnosed her with an acute schizoaffective disorder given the additional history of underlying psychological stressors (it was the death anniversary of her mother, and her final high-school national examinations were imminent). She was admitted and treated with psychotropic medication, but after five days she developed documented fevers, orofacial dyskinesias with tongue-biting, and agitation, and she was additionally treated for neuroleptic malignant syndrome (NMS). She then became comatose and was thus transferred to our tertiary referral hospital.
On our initial assessment, she had a temperature of 39 C and tachycardia; neurologically her Glasgow Coma Scale (GCS) was 7/15, she had grimacing, tongue biting, bruxism, hyper-salivation and abnormal arm movements which were difficult to classify (Figure 1, Supplementary Video S1). She was intubated, mechanically ventilated and admitted to the intensive care unit (ICU).
We immediately ran investigations comprehensive blood and/or urine tests for infection, auto-immune disease (including vasculitis) and toxic causes (including porphyria), also comprising polymerase chain reaction (PCR) for tropical fever pathogens (human immunodeficiency virus, Treponema pallidum, malaria, Leptospira, rickettsia, dengue, West Nile, chikungunya and rabies viruses - with additional testing in saliva and neck hairline skin biopsies for the latter), contrast-enhanced computed tomography scan of the head, chest and abdomen which were all normal/negative.
Examination of her cerebrospinal fluid (CSF) revealed elevated pressures, and white cell count of 115/mm3, 98% lymphocytes, with negative PCR for bacterial, tuberculosis and herpes (simplex and varicella zoster) meningo-encephalitis pathogens (including on repeat CSF on day 2). Contrast-enhanced MRI brain scan demonstrated leptomeningeal enhancement (Figure 2A) with corresponding sulcal hyperintensities (Figure 2B) and serial electroencephalography (EEG) showed non-specific diffuse slowing with no epileptiform discharges.
She was initially treated for viral encephalitis, but this was stopped after two negative PCRs in CSF. After two further independent neurology opinions in addition to the primary neurologist (author DSS), we diagnosed the patient with probable NMDARE as defined by international criteria and commenced immunosuppression with high-dose intravenous methylprednisolone (IVMP) 1 gram/day for five days and concurrent intravenous immunoglobulins. The orofacial and upper limb movement disorders were controlled with a combination of oral levetiracetam and tetrabenazine, midazolam and propofol infusions, and maxillo-mandibular fixation. On day 7 both serum and CSF autoimmune encephalitis panels returned positive for antibodies against the NMDA receptor, giving a definite diagnosis of NMDARE. MRI pelvis did not show any ovarian or extra-gonadal teratoma.
At day 15 repeat MRI brain scan showed almost complete resolution of the meningeal enhancement (Figure 2C) and sulcal hyperintensities (Figure 2D) but her GCS remained persistently low at 8/15 and her unrelenting dyskinesias required higher sedation requirements. We repeated the IVMP course now with concurrent plasma exchange and weekly rituximab dosed at 375mg/m2 body surface area. Her ICU stay was complicated by right brachial deep vein thrombosis treated with low-molecular weight heparin, and tongue maceration that required surgical debridement. She had both tracheostomy and percutaneous endoscopic gastrostomy tubes fixed due to the prolonged ICU admission.
During the fourth week, she developed high-grade fevers due to multi-drug resistant Pseudomonas aeruginosa and Klebsiella pneumoniae, isolated from tracheal aspirates and the tracheostomy site. Despite timely initiation of appropriate intravenous antibiotics including carbapenems and continued debridement of the tracheostomy site, the patient went into septic shock leading to multi-organ dysfunction and succumbed 30 days into her hospital stay. | anti-nmda receptor encephalitis, auto-immune encephalitis, sub-saharan africa | Not supported with pagination yet | null |
PMC7728127_01 | Female | 0 | Legal perspective on abortion
In Romania, abortion was brought under regulation by the first Criminal Code of the United Principalities, from 1864.
The Criminal Code from 1864, provided the abortion infringement in Article 246, on which was regulated as follows: "Any person, who, using means such as food, drinks, pills or any other means, which will consciously help a pregnant woman to commit abortion, will be punished to a minimum reclusion (three years).
The woman who by herself shall use the means of abortion, or would accept to use means of abortion which were shown or given to her for this purpose, will be punished with imprisonment from six months to two years, if the result would be an abortion. In a situation where abortion was carried out on an illegitimate baby by his mother, the punishment will be imprisonment from six months to one year.
Doctors, surgeons, health officers, pharmacists (apothecary) and midwives who will indicate, will give or will facilitate these means, shall be punished with reclusion of at least four years, if the abortion took place. If abortion will cause the death of the mother, the punishment will be much austere of four years" (Art. 246).
The Criminal Code from 1864, reissued in 1912, amended in part the Article 246 for the purposes of eliminating the abortion of an illegitimate baby case. Furthermore, it was no longer specified the minimum of four years of reclusion, in case of abortion carried out with the help of the medical staff, leaving the punishment to the discretion of the Court (Art. 246).
The Criminal Code from 1936 regulated abortion in the Articles 482-485. Abortion was defined as an interruption of the normal course of pregnancy, being punished as follows:
"1. When the crime is committed without the consent of the pregnant woman, the punishment was reformatory imprisonment from 2 to 5 years. If it caused the pregnant woman any health injury or a serious infirmity, the punishment was reformatory imprisonment from 3 to 6 years, and if it has caused her death, reformatory imprisonment from 7 to 10 years;
2. When the crime was committed by the unmarried pregnant woman by herself, or when she agreed that someone else should provoke the abortion, the punishment is reformatory imprisonment from 3 to 6 months, and if the woman is married, the punishment is reformatory imprisonment from 6 months to one year. Same penalty applies also to the person who commits the crime with the woman's consent. If abortion was committed for the purpose of obtaining a benefit, the punishment increases with another 2 years of reformatory imprisonment.
If it caused the pregnant woman any health injuries or a severe disablement, the punishment will be reformatory imprisonment from one to 3 years, and if it has caused her death, the punishment is reformatory imprisonment from 3 to 5 years" (Art. 482).
The criminal legislation from 1936 specifies that it is not considered as an abortion the interruption from the normal course of pregnancy, if it was carried out by a doctor "when woman's life was in imminent danger or when the pregnancy aggravates a woman's disease, putting her life in danger, which could not be removed by other means and it is obvious that the intervention wasn't performed with another purpose than that of saving the woman's life" and "when one of the parents has reached a permanent alienation and it is certain that the child will bear serious mental flaws" (Art. 484, Par. 1 and Par. 2).
In the event of an imminent danger, the doctor was obliged to notify prosecutor's office in writing, within 48 hours after the intervention, on the performance of the abortion. "In the other cases, the doctor was able to intervene only with the authorization of the prosecutor's office, given on the basis of a medical certificate from hospital or a notice given as a result of a consultation between the doctor who will intervene and at least a professor doctor in the disease which caused the intervention. General's Office Prosecutor, in all cases provided by this Article, shall be obliged to maintain the confidentiality of all communications or authorizations, up to the intercession of any possible complaints" (Art. 484).
The legislation of 1936 provided a reformatory injunction from one to three years for the abortions committed by doctors, sanitary agents, pharmacists, apothecary or midwives (Art. 485).
Abortion on demand has been legalized for the first time in Romania in the year 1957 by the Decree No. 463, under the condition that it had to be carried out in a hospital and to be carried out in the first quarter of the pregnancy. In the year 1966, demographic policy of Romania has dramatically changed by introducing the Decree No. 770 from September 29th, which prohibited abortion. Thus, the voluntary interruption of pregnancy became a crime, with certain exceptions, namely: endangering the mother's life, physical or mental serious disability; serious or heritable illness, mother's age over 45 years, if the pregnancy was a result of rape or incest or if the woman gave birth to at least four children who were still in her care (Art. 2).
In the Criminal Code from 1968, the abortion crime was governed by Articles 185-188.
The Article 185, "the illegal induced abortion", stipulated that "the interruption of pregnancy by any means, outside the conditions permitted by law, with the consent of the pregnant woman will be punished with imprisonment from one to 3 years". The act referred to above, without the prior consent from the pregnant woman, was punished with prison from two to five years. If the abortion carried out with the consent of the pregnant woman caused any serious body injury, the punishment was imprisonment from two to five years, and when it caused the death of the woman, the prison sentence was from five to 10 years. When abortion was carried out without the prior consent of the woman, if it caused her a serious physical injury, the punishment was imprisonment from three to six years, and if it caused the woman's death, the punishment was imprisonment from seven to 12 years (Art. 185).
"When abortion was carried out in order to obtain a material benefit, the maximum punishment was increased by two years, and if the abortion was made by a doctor, in addition to the prison punishment could also be applied the prohibition to no longer practice the profession of doctor".
Article 186, "abortion caused by the woman", stipulated that "the interruption of the pregnancy course, committed by the pregnant woman, was punished with imprisonment from 6 months to 2 years", quoting the fact that by the same punishment was also sanctioned "the pregnant woman's act to consent in interrupting the pregnancy course made out by another person" (Art. 186).
The Regulations of the Criminal Code in 1968, also provided the crime of "ownership of tools or materials that can cause abortion", the conditions of this holding being met when these types of instruments were held outside the hospital's specialized institutions, the infringement shall be punished with imprisonment from three months to one year (Art. 187).
Furthermore, the doctors who performed an abortion in the event of extreme urgency, without prior legal authorization and if they did not announce the competent authority within the legal deadline, they were punished by imprisonment from one month to three months (Art. 188).
In the year 1985, it has been issued the Decree No. 411 of December 26th, by which the conditions imposed by the Decree No. 770 of 1966 have been hardened, meaning that it has increased the number of children, that a woman could have in order to request an abortion, from four to five children.
The Articles 185-188 of the Criminal Code and the Decree No. 770/1966 on the interruption of the pregnancy course have been abrogated by Decree-Law No. 1 from December 26th, 1989, which was published in the Official Gazette No. 4 of December 27th, 1989 (Par. 8 and Par. 12).
The Criminal Code from 1968, reissued in 1997, maintained Article 185 about "the illegal induced abortion", but drastically modified. Thus, in this case of the Criminal Code, we identify abortion as "the interruption of pregnancy course, by any means, committed in any of the following circumstances: (a) outside medical institutions or authorized medical practices for this purpose; (b) by a person who does not have the capacity of specialized doctor; (c) if age pregnancy has exceeded 14 weeks", the punishment laid down was the imprisonment from 6 months to 3 years" (Art. 185, Par. 1). For the abortion committed without the prior consent of the pregnant woman, the punishment consisted in strict prison conditions from two to seven years and with the prohibition of certain rights (Art. 185, Par. 2).
For the situation of causing serious physical injury to the pregnant woman, the punishment was strict prison from three to 10 years and the removal of certain rights, and if it had as a result the death of the pregnant woman, the punishment was strict prison from five to 15 years and the prohibition of certain rights (Art. 185, Par. 3).
The attempt was punished for the crimes specified in the various cases of abortion.
Consideration should also be given in the Criminal Code reissued in 1997 for not punishing the interruption of the pregnancy course carried out by the doctor, if this interruption "was necessary to save the life, health or the physical integrity of the pregnant woman from a grave and imminent danger and that it could not be removed otherwise; in the case of a over fourteen weeks pregnancy, when the interruption of the pregnancy course should take place from therapeutic reasons" and even in a situation of a woman's lack of consent, when it has not been given the opportunity to express her will, and abortion "was imposed by therapeutic reasons" (Art. 185, Par. 4).
Criminal Code from 2004 covers abortion in Article 190, defined in the same way as in the prior Criminal Code, with the difference that it affects the limits of the punishment. So, in the event of pregnancy interruption, in accordance with the conditions specified in Paragraph 1, "the penalty provided was prison time from 6 months to one year or days-fine" (Art. 190, Par. 1).
Nowadays, in Romania, abortion is governed by the criminal law of 2009, which entered into force in 2014, by the section called "aggression against an unborn child". It should be specified that current criminal law does not punish the woman responsible for carrying out abortion, but only the person who is involved in carrying out the abortion. There is no punishment for the pregnant woman who injures her fetus during pregnancy.
In Article 201, we can find the details on the pregnancy interruption infringement. Thus, the pregnancy interruption can be performed in one of the following circumstances: "outside of medical institutions or medical practices authorized for this purpose; by a person who does not have the capacity of specialist doctor in Obstetrics and Gynecology and the right of free medical practice in this specialty; if gestational age has exceeded 14 weeks", the punishment is the imprisonment for six months to three years, or fine and the prohibition to exercise certain rights (Art. 201, Par. 1).
Article 201, Paragraph 2 specifies that "the interruption of the pregnancy committed under any circumstances, without the prior consent of the pregnant woman, can be punished with imprisonment from 2 to 7 years and with the prohibition to exercise some rights" (Art. 201, Par. 1).
If by facts referred to above (Art. 201, Par. 1 and Par. 2) "it has caused the pregnant woman's physical injury, the punishment is the imprisonment from 3 to 10 years and the prohibition to exercise some rights, and if it has had as a result the pregnant woman's death, the punishment is the imprisonment from 6 to 12 years and the prohibition to exercise some rights" (Art. 201, Par. 3). When the facts have been committed by a doctor, "in addition to the imprisonment punishment, it will also be applied the prohibition to exercise the profession of doctor (Art. 201, Par. 4).
Criminal legislation specifies that "the interruption of pregnancy does not constitute an infringement with the purpose of a treatment carried out by a specialist doctor in Obstetrics and Gynecology, until the pregnancy age of twenty-four weeks is reached, or the subsequent pregnancy interruption, for the purpose of treatment, is in the interests of the mother or the fetus" (Art. 201, Par. 6). However, it can all be found in the phrases "therapeutic purposes" and "the interest of the mother and of the unborn child", which predisposes the text of law to an interpretation, finally the doctors are the only ones in the position to decide what should be done in such cases, assuming direct responsibility.
Article 202 of the Criminal Code defines the crime of harming an unborn child, pointing out the punishments for the various types of injuries that can occur during pregnancy or in the childbirth period and which can be caused by the mother or by the persons who assist the birth, with the specification that the mother who harms her fetus during pregnancy is not punished and does not constitute an infringement if the injury has been committed during pregnancy or during childbirth period if the facts have been "committed by a doctor or by an authorized person to assist the birth or to follow the pregnancy, if they have been committed in the course of the medical act, complying with the specific provisions of his profession and have been made in the interest of the pregnant woman or fetus, as a result of the exercise of an inherent risk in the medical act" (Art. 202, Par. 6).
The fact situation in Romania
During the period 1948-1955, called "the small baby boom", Romania registered an average fertility rate of 3.23 children for a woman. Between 1955 and 1962, the fertility rate has been less than three children for a woman, and in 1962, fertility has reached an average of two children for a woman. This phenomenon occurred because of the Decree No. 463/1957 on liberalization of abortion. After the liberalization from 1957, the abortion rate has increased from 220 abortions per 100 born-alive children in the year 1960, to 400 abortions per 100 born-alive children, in the year 1965.
The application of provisions of Decrees No. 770 of 1966 and No. 411 of 1985 has led to an increase of the birth rate in the first three years (an average of 3.7 children in 1967, and 3.6 children in 1968), followed by a regression until 1989, when it was recorded an average of 2.2 children, but also a maternal death rate caused by illegal abortions, raising up to 85 deaths of 100 000 births in the year of 1965, and 170 deaths in 1983. It was estimated that more than 80% of maternal deaths between 1980-1989 was caused by legal constraints.
After the Romanian Revolution in December 1989 and after the communism fall, with the abrogation of Articles 185-188 of the Criminal Code and of the Decree No. 770/1966, by the Decree of Law No. 1 of December 26th, 1989, abortion has become legal in Romania and so, in the following years, it has reached the highest rate of abortion in Europe. Subsequently, the number of abortion has dropped gradually, with increasing use of birth control.
Statistical data issued by the Ministry of Health and by the National Institute of Statistics (INS) in Romania show corresponding figures to a legally carried out abortion. The abortion number is much higher, if it would take into account the number of illegal abortion, especially those carried out before 1989, and those carried out in private clinics, after the year 1990. Summing the declared abortions in the period 1958-2014, it is to be noted the number of them, 22 037 747 exceeds the current Romanian population. A detailed statistical research of abortion rate, in terms of years we have exposed in Table 1.
Data issued by the United Nations International Children's Emergency Fund (UNICEF) in June 2016, for the period 1989-2014, in matters of reproductive behavior, indicates a fertility rate for Romania with a continuous decrease, in proportion to the decrease of the number of births, but also a lower number of abortion rate reported to 100 deliveries (Table 2).
By analyzing data issued for the period 1990-2015 by the International Organization of Health, UNICEF, United Nations Fund for Population Activity (UNFPA), The World Bank and the United Nations Population Division, it is noticed that maternal mortality rate has currently dropped as compared with 1990 (Table 3).
Opinion survey: women's opinion on abortion
Argument for choosing the research theme
Although the problematic on abortion in Romania has been extensively investigated and debated, it has not been carried out in an ample sociological study, covering Romanian women's perception on abortion. We have assumed making a study at national level, in order to identify the opinion on abortion, on the motivation to carry out an abortion, and to identify the correlation between religious convictions and the attitude toward abortion.
Examining the literature field of study
In the conceptual register of the research, we have highlighted items, such as the specialized literature, legislation, statistical documents.
Formulation of hypotheses and objectives
The first hypothesis was that Romanian women accept abortion, having an open attitude towards this act. Thus, the first objective of the research was to identify Romanian women's attitude towards abortion.
The second hypothesis, from which we started, was that high religious beliefs generate a lower tolerance towards abortion. Thus, the second objective of our research has been to identify the correlation between the religious beliefs and the attitude towards abortion.
The third hypothesis of the survey was that, the main motivation in carrying out an abortion is the fact that a woman does not want a baby, and the main motivation for keeping the pregnancy is that the person wants a baby. In this context, the third objective of the research was to identify main motivation in carrying out an abortion and in maintaining a pregnancy.
Another hypothesis was that modern Romanian legislation on the abortion is considered fair. Based on this hypothesis, we have assumed the fourth objective, which is to identify the degree of satisfaction towards the current regulatory provisions governing the abortion.
Research methodology
The research method is that of a sociological survey by the application of the questionnaire technique. We used the sampling by age and residence looking at representative numbers of population from more developed as well as underdeveloped areas.
Determination of the sample to be studied
Because abortion is a typical women's experience, we have chosen to make the quantitative research only among women. We have constructed the sample by selecting a number of 1260 women between the ages of 15 and 44 years (the most frequently encountered age among women who give birth to a child). We also used the quota sampling techniques, taking into account the following variables: age group and the residence (urban/rural), so that the persons included in the sample could retain characteristic of the general population.
By the sample of 1260 women, we have made a percentage of investigation of 0.03% of the total population.
The Questionnaires number applied was distributed as follows (Table 4).
Data collection
Data collection was carried out by questionnaires administered by 32 field operators between May 1st-May 31st, 2018.
The analysis of the research results
In the next section, we will present the main results of the quantitative research carried out at national level.
Almost three-quarters of women included in the sample agree with carrying out an abortion in certain circumstances (70%) and only 24% have chosen to support the answer "No, never". In modern contemporary society, abortion is the first solution of women for which a pregnancy is not desired. Even if advanced medical techniques are a lot safer, an abortion still carries a health risk. However, 6% of respondents agree with carrying out abortion regardless of circumstances (Table 5).
Although abortions carried out after 14 weeks are illegal, except for medical reasons, more than half of the surveyed women stated they would agree with abortion in certain circumstances. At the opposite pole, 31% have mentioned they would never agree on abortions after 14 weeks. Five percent were totally accepting the idea of abortion made to a pregnancy that has exceeded 14 weeks (Table 6).
For 53% of respondents, abortion is considered a crime as well as the right of a women. On the other hand, 28% of the women considered abortion as a crime and 16% associate abortion with a woman's right (Table 7).
Opinions on what women abort at the time of the voluntary pregnancy interruption are split in two: 59% consider that it depends on the time of the abortion, and more specifically on the pregnancy development stage, 24% consider that regardless of the period in which it is carried out, women abort a child, and 14% have opted a fetus (Table 8).
Among respondents who consider that women abort a child or a fetus related to the time of abortion, 37.5% have considered that the difference between a baby and a fetus appears after 14 weeks of pregnancy (the period legally accepted for abortion). Thirty-three percent of them have mentioned that the distinction should be performed at the first few heartbeats; 18.1% think it is about when the child has all the features definitively outlined and can move by himself; 2.8% consider that the difference appears when the first encephalopathy traces are being felt and the child has formed all internal and external organs. A percentage of 1.7% of respondents consider that this difference occurs at the beginning of the central nervous system, and 1.4% when the unborn child has all the features that we can clearly see to a newborn child (Table 9).
We noticed that highly religious people make a clear association between abortion and crime. They also consider that at the time of pregnancy interruption it is aborted a child and not a fetus. However, unexpectedly, we noticed that 27% of the women, who declare themselves to be very religious, have also stated that they see abortion as a crime but also as a woman's right. Thirty-one percent of the women, who also claimed profound religious beliefs, consider that abortion may be associated with the abortion of a child but also of a fetus, this depending on the time of abortion (Tables 10 and 11).
More than half of the respondents have opted for the main reason for abortion the appearance of medical problems to the child. Baby's health represents the main concern of future mothers, and of each parent, and the birth of a child with serious health issues, is a factor which frightens any future parent, being many times, at least theoretically, one good reason for opting for abortion. At the opposite side, 12% of respondents would not choose abortion under any circumstances. Other reasons for which women would opt for an abortion are: if the woman would have a medical problem (22%) or would not want the child (10%) (Table 12).
Most of the women want to give birth to a child, 56% of the respondents, representing also the reason that would determine them to keep the child. Morality (26%), faith (10%) or legal restrictions (4%), are the three other reasons for which women would not interrupt a pregnancy. Only 2% of the respondents have mentioned other reasons such as health or age.
A percentage of 23% of the surveyed people said that they have done an abortion so far, and 77% did not opted for a surgical intervention either because there was no need, or because they have kept the pregnancy (Table 13).
Most respondents, 87% specified that they have carried out an abortion during the first 14 weeks - legally accepted limit for abortion: 43.6% have made abortion in the first four weeks, 39.1% between weeks 4-8, and 4.3% between weeks 8-14. It should be noted that 8.7% could not appreciate the pregnancy period in which they carried out abortion, by opting to answer with the option "I don't know", and a percentage of 4.3% refused to answer to this question.
Performing an abortion is based on many reasons, but the fact that the women have not wanted a child is the main reason mentioned by 47.8% of people surveyed, who have done minimum an abortion so far. Among the reasons for the interruption of pregnancy, it is also included: women with medical problems (13.3%), not the right time to be a mother (10.7%), age motivation (8.7%), due to medical problems of the child (4.3%), the lack of money (4.3%), family pressure (4.3%), partner/spouse did not wanted. A percentage of 3.3% of women had different reasons for abortion, as follows: age difference too large between children, career, marital status, etc. Asked later whether they regretted the abortion, a rate of 69.6% of women who said they had at least one abortion regret it (34.8% opted for "Yes", and 34.8% said "Yes, partially"). 26.1% of surveyed women do not regret the choice to interrupted the pregnancy, and 4.3% chose to not answer this question. We noted that, for women who have already experienced abortion, the causes were more diverse than the grounds on which the previous question was asked: "What are the reasons that determined you to have an abortion?" (Table 14).
The majority of the respondents (37.5%) considered that "nervous depression" is the main consequence of abortion, followed by "insomnia and nightmares" (24.6%), "disorders in alimentation" and "affective disorders" (each for 7.7% of respondents), "deterioration of interpersonal relationships" and "the feeling of guilt"(for 6.3% of the respondents), "sexual disorders" and "panic attacks" (for 6.3% of the respondents) (Table 15).
Over half of the respondents believe that abortion should be legal in certain circumstances, as currently provided by law, 39% say it should be always legal, and only 6% opted for the illegal option (Table 16).
Although the current legislation does not punish pregnant women who interrupt pregnancy or intentionally injured their fetus, survey results indicate that 61% of women surveyed believe that the national law should punish the woman and only 28% agree with the current legislation (Table 17).
For the majority of the respondents (40.6%), the penalty provided by the current legislation, the imprisonment between six months and three years or a fine and deprivation of certain rights for the illegal abortion is considered fair, for a percentage of 39.6% the punishment is too small for 9.5% of the respondents is too high. Imprisonment between two and seven years and deprivation of certain rights for an abortion performed without the consent of the pregnant woman is considered too small for 65% of interviewees. Fourteen percent of them think it is fair and only 19% of respondents consider that Romanian legislation is too severe with people who commit such an act considering the punishment as too much. The imprisonment from three to 10 years and deprivation of certain rights for the facts described above, if an injury was caused to the woman, is considered to be too small for more than half of those included in the survey, 64% and almost 22% for nearly a quarter of them. Only 9% of the respondents mentioned that this legislative measure is too severe for such actions (Table 18). | null | Not supported with pagination yet | null |
PMC6334334_01 | Male | 74 | A 74-year-old male patient underwent left total knee arthroplasty (TKA) at our institution for degenerative knee osteoarthrosis. He had an uneventful postoperative course with no history of delayed wound healing or persistent drainage. Four years later, he presented with a 2-month history of a gradually developing painless swelling over the anterior aspect of the operated knee; the swelling was associated with a small sinus that was extruding a straw-coloured fluid. He had no history of fever, decreased appetite, or weight loss. He had no other musculoskeletal, respiratory, or systemic symptoms of note. He had no history of antecedent trauma, recent travel, or contact with infectious diseases. The patient is a known hypertensive, but the blood pressure was well controlled with treatment, and he is otherwise healthy. He is a retired teacher with no history of involvement in activities requiring excessive kneeling. He is ambulatory in his community and can walk comfortably with the assistance of a cane.
The patient's general physical examination results were within normal limits; positive physical findings were limited to the involved knee. There was an anterior knee swelling involving mainly the prepatellar area, approximately 7 cm in diameter, fluctuant, and not tender to palpation, with minimal surrounding erythema; the erythema was present mainly at the punctum. The punctum was draining a yellowish discharge on pressure (Figure 1(a)). There was no bony tenderness at the patella, distal femur, or proximal tibia. There was no detectable knee effusion, instability, or crepitus. The range of motion was well preserved (5-110 ), as it was a prosthetic knee. It was only painful at the end of flexion as this movement compressed the prepatellar bursa.
Plain radiographs of the knee showed a prepatellar soft tissue swelling (Figure 2(a)). There were no obvious bony changes, osteolysis, or loosening at the bone-prosthesis interface. Needle aspiration of the prepatellar bursa yielded 50 mL of slightly turbid straw-coloured yellowish fluid that was sent as per our protocol for cell count determination, microcrystal analysis, Gram staining, and Ziehl-Neelsen (ZN) staining for acid-fast bacilli (Figure 1(b)). Cultures for aerobic and anaerobic bacteria, Mycobacterium tuberculosis, Brucella, and fungi were requested.
Considering the patient's age, chronic presentation, and the presence of sinus, he was admitted with a diagnosis of infected prepatellar bursitis. The primary aims of admission were wound dressing, awaiting aspiration results, and further work-up. Aspiration results revealed normal cell counts, no crystals, and no organisms on Gram stain. To our surprise, ZN stain revealed acid-fast bacilli consistent with typical tuberculous infection; the bacterium was confirmed on culture 6 weeks later as Mycobacterium tuberculosis-sensitive to rifampicin, isoniazid, ethambutol, and streptomycin. Cultures for bacteria, Brucella, and fungi were negative. Aspiration was repeated and yielded similar results. The blood work-up showed normal total and differential white blood cell count and slight elevation of both erythrocyte sedimentation rate (ESR) (80 mm/hr; normal: 30-70 mm/hr) and C-reactive protein (CRP) (8 mg/L; normal: 0-4 mg/L). Tuberculin skin test revealed a negative result (<5 mm induration at 72 hrs), and further work-up including chest radiograph and echocardiogram revealed no evidence of systemic disease. A triple three-phase bone scan displayed normal uptake both at the bone-prosthesis interface and at the patella. An infectious disease consult was obtained. The patient was started on rifampicin (600 mg/day), isoniazid (300 mg/day), pyrazinamide (1500 mg/day), and ethambutol (800 mg/day) for 2 months and continued on the same dosage of rifampicin and isoniazid to complete a 6-month course.
Three weeks later, the swelling significantly subsided in size and the sinus healed; therefore, the patient was discharged. He was reviewed at 6-week intervals at both the orthopaedic and infectious disease clinics for clinical progression and for any side effects of the medication. At the most recent 6-year follow-up, he was doing well with no evidence of local recurrence or prosthetic loosening (Figure 2(b)). | null | Not supported with pagination yet | null |
PMC9493008_01 | Male | 59 | In December 2019, a 59-year-old male (non-smoker) was admitted to our center due to cough for two weeks. The contrast-enhanced thoracic computed tomography (CT) revealed a primary lesion (lesion 1, 92x58 mm) in the right upper lobe of the lung and multiple metastases with a maximum size of 37x24 mm (lesion 2) in the left lower lobe of the lung, and distant spread to mediastinal lymph nodes was suspected ( Figures 1A, B ). Pathological investigations were performed on the lymph node specimens obtained by EBUS-TBNA, and the findings were, as follows: lung adenocarcinoma ( Figure 2A ) with TTF-1(+) ( Figure 2B ), NapsinA(+) ( Figure 2C ), CK7(+) ( Figure 2D ), D2-40(-), CD56(-), Wilms tumor(-), Caplonin(-), CDX-2(-), SATB2(-), Ki67(60% +), EGFR exon19 deletion and PD-L1 TPS 15%. Finally, the diagnosis of lung adenocarcinoma (T4N3M1a, stage IVA) with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 1 was made based on the clinical findings. Then, 125 mg of icotinib was orally administered, three times daily.
In March 2020, the thoracic CT revealed that the primary tumor and metastases decreased in size ( Figures 1C, D ): lesion 1 (42x39 mm) and lesion 2 (20x15 mm). Partial remission was also considered. However, in June 2020, the two lesions mentioned above enlarged (lesion 1, 100x80 mm; lesion 2, 65x62 mm), and a new lesion (lesion 3, 15x9 mm) was found in the right lower lobe ( Figures 1E, F ). Furthermore, multiple metastases were found in the left cerebellum and right frontal lobe by brain magnetic resonance imaging (MRI, Figure 1G ). Therefore, the clinical response was evaluated as a progressive disease. The treatment was changed to pemetrexed (940 mg/day) and carboplatin (600 mg/day). The plasma next-generation sequencing (NGS) test revealed an EGFR T790M mutation, and that the EGFR exon 19 deletion did not disappear. Then, 80 mg of osimertinib was orally administered, once daily.
In July 2020, lesion 1 (69x41 mm, Figures 1H, I ), lesion 2 (30x18 mm), and lesion 3 (10x6 mm) all decreased in size. Furthermore, an improvement was revealed by the brain MRI. The response was considered as partial remission. However, in August 2020, lesion 3 increased in size (25x14 mm, Figure 1J ), and the pathological evidence of lung biopsies obtained by CT-guided procedures confirmed the squamous cell carcinoma ( Figure 2E ) with P40(+) ( Figure 2F ), CK5/6(+) ( Figure 2G ), CK7(-), NapsinA(-), TTF-1(-), CgA(-), CD56(-), Syn(-), Ki67(30% +), EGFR exon19 deletion, T790M mutant, MET amplification (high-throughput sequencing), and PD-L1 TPS 20%.
After the multi-disciplinary team (MDT) discussion, pembrolizumab (200 mg/day), paclitaxel liposome (250 mg/day) and carboplatin (600 mg/day) were incorporated into the present treatment with osimertinib. After two cycles of chemotherapy, in October 2020, a stable condition was suggested by the thoracic CT (lesion 1, 70x42 mm; lesion 2, 32x21 mm; lesion 3, 10x5 mm) and brain MRI (no obvious changes). Subsequently, the patient refused further chemotherapy, and only pembrolizumab was given for the third cycle of therapy. After one week, due to suspicion of cardiac injury, the use of pembrolizumab was interrupted, and osimertinib and crizotinib (250 mg, three times daily) were administered after the MDT meeting. The thoracic CT findings revealed that the patient's condition improved again: lesion 1 (65x40 mm), lesion 2 (26x17 mm), and lesion 3 (disappeared). However, transient strabismus and unconsciousness suddenly occurred, and a lesion in the brain developed, as revealed by the MRI, which was treated with low-dose radiotherapy at 24 Gy in eight fractions.
In January 2021, the thoracic CT findings (lesion 1, 73x54 mm; lesion 2, 33x26 mm) revealed that the patient's condition developed. This situation was further confirmed in May 2021 by CT imaging, and the ECOG-PS score was evaluated as 2. The treatment was switched to pembrolizumab (200 mg/day) and anlotinib (8 mg, three times daily, every three weeks, with one week intervals). In June 2021, the disease developed with enlarged lesions (lesion 1, 57x78 mm; lesion 2, 60x84 mm). Progressive status was considered, and the ECOG-PS score was evaluated as 3. Then, treatment with everolimus was initiated (5 mg, three times daily). Finally, the patient died in August 2021. | adenocarcinoma, epidermal growth factor receptor, squamous cell carcinoma, transformation, tyrosine kinase inhibitor | Not supported with pagination yet | null |
PMC8047292_01 | Male | 47 | A 47-year-old man was referred to the emergency room in our hospital with swollen and painful right eye and face which had lasted 8 days. 3 days prior admission, the swelling seemed to be worsening and there was release of the pus.
The patient had a history of toothache since 2 years ago and bloody cough since 5 months ago. Further investigation did not revealed any history of trauma.
On admission, the patient presented with drowsiness, paleness, and fever. Visual acuity of the right eye was only light perception with limited eye movement in all directions. Examination revealed (Fig 1) non-axial proptosis, swelling of upper and lower eyelid with purulent discharge, chemosis, and purulent discharge on conjunctival bulbi and hazy cornea. There was fistula on right mandible to inner buccal which released pus.
Imaging modalities using CT scan (fig 2) revealed orbital sub-tissue swelling and sub-periosteal abscess on the upper lateral orbital wall. The laboratory test showed leukocytosis and elevated level erythrocyte sedimentation rate. A tentative diagnosis of orbital cellulitis with abscess formation was made. The patient was treated with intravenous ceftriaxone and metronidazole injection. The incision and drainage procedure was performed. The pus was collected, gram staining performed and culture done immediately.
We treated the patient conservatively in closed observation. On 3rd day of treatment, patient still had fever, cough, swelling on the right eye and face with active pus production. We ordered sputum smear microscopy test and chest X-rays. On the 5th day, the culture of the pus was confirmed using identification (ID) and antimicrobial susceptibility testing (AST), BD Phoenix (BD Diagnostic Systems, Sparks, MD) as extended spectrum beta-lactamases (ESBLs) producing Escherichia coli and Staphylococcus cohnii ssp urealyticum with susceptibility to ampicilin-sulbactam. Ziehl-Neelson staining test (fig 3) revealed acid fast bacillus with pulmonary inflammation highly pathognomonic of tuberculosis. Based on the culture result, the antibiotic regimen was modified through a consultation with pulmonary division and patient was scheduled to receive fixed doses combinations (FDC) for tuberculosis. We managed patient with intravenous ampicillin sulbactam, intravenous metronidazole, with irrigation and drainage of the abscess once a day.
On the 11th day, the swelling and abscess were resolved, followed by systemic condition improvement. The patient was discharged (fig 4) from the hospital on the 15th day in stable systemic condition with visual acuity hand movement on the right eye. | extended spectrum β-lactamases, orbital cellulitis, pulmonary tuberculosis | Not supported with pagination yet | null |
PMC6016216_01 | Male | 55 | A 55-year-old gentleman, ex-smoker, presented to our hospital complaining of mild epigastric pain, regurgitation, and heartburn. On top of that, he has a long-standing history of gastroesophageal reflux disease (GERD), which was managed by proton pump inhibitors. His past medical history was significant for hypertension. He was previously diagnosed with a liver hemangioma based on abdominal ultrasound two years before the presentation. He had no relevant family history. Physical examination revealed mild epigastric tenderness with no palpable abdominal mass. Laboratory data showed no anemia but positive stool occult blood test. Tumor markers including AFP, CEA, and CA 19-9 were all within normal range. Upper GI endoscopy revealed mild esophagitis, Los Angles grade A along with Barrett's esophagus without dysplasia and a 1 cm polyp at the GEJ. A sample was sent for histopathology; the rest of the stomach and duodenum were normal. The patient did not have a previous endoscopy prior to this one.
Infused computed tomography (CT) of the abdomen and chest showed mild GEJ thickness with no evidence of mediastinal or celiac lymphadenopathy and no signs of metastasis. It also demonstrated a large heterogeneously enhancing mass about 6 x 9.5 cm with central necrosis in the upper abdomen that appears to be originating from the gastric antrum (greater curve). The mass was highly suggestive of GIST based on CT; it was the same mass that was previously misdiagnosed as a liver hemangioma (Figure 1). Endoscopic ultrasound confirmed the previous findings. However, no biopsy was attempted due to the risk of bleeding.
Histopathological examination of the GEJ polyp revealed tubulovillous adenoma with elements of adenocarcinoma in situ. The patient was admitted with a provisional diagnosis of early-stage adenocarcinoma of GEJ along with the incidental finding of enlarging gastric GIST. A trial of endoscopic mucosal resection of GEJ polyp was attempted but failed because of the polyp location that created a technical difficulty. Therefore, the patient was taken to the operating room with a plan to perform a wedge resection of the gastric mass and a submucosal resection of GEJ polyp through the same gastric opening. We planned to use frozen section (FS) to document negative margin resection and determine the need for a formal esophagectomy. Intraoperatively; a large (10 x 7 x 6 cm), extraluminal pedunculated mass was found at the posterior wall of the greater curvature of the stomach (Figure 2). Wedge resection of the gastric mass with negative margins was achieved along with a transgastric submucosal resection of the GEJ polyp. Fortunately, the FS examination of the polyp showed negative margins as well with no evidence of deep invasion. Postoperatively, the patient had a smooth course and was discharged home in a stable condition. The final pathological examination revealed a GEJ polyp around 1.7 x 1.4 x 0.6 cm. Microscopically, there was a focus of invasive adenocarcinoma involving the superficial submucosa of the polypoid lesion, negative margins, and no lymphovascular invasion (T1a NxM0). Furthermore, the gastric wall mass measured around 10 x 7 x 6 cm with a 2 x 1.5 cm stalk. Histopathology revealed encapsulated high-grade epithelioid GIST tumor with negative margins (pT3). The mitotic rate of 6/50 HPF and immunohistochemical stains were positive for DOG1 and CD34 but negative for CD117 (c-Kit) (Figure 3).
The final diagnosis was synchronous early-stage GEJ adenocarcinoma and a high-grade gastric GIST. Therefore, the patient was started on adjuvant imatinib treatment, along with endoscopic surveillance every six months and proton pump inhibitors. | null | Not supported with pagination yet | null |
PMC7494786_01 | Male | 65 | A 65-year-old man with poorly controlled diabetes and hypertension reported progressive otalgia and otorrhea in his left ear for 8 months. He was only treated with symptomatic medications in the emergency services during this time. Five months later, he noticed loss of visual acuity in the left eye and hearing loss in the left ear, progressing soon after with left peripheral facial palsy. During the next two months, he evolved with left eye proptosis (Figs. 1 and 2 ), complete visual loss and ophthalmoplegia (Figs. 1 and 2), in addition to hearing loss in the right ear. He was initially evaluated by a primary care otorhinolaryngologist, who suspected the diagnosis of MEO and initiated ciprofloxacin 500 mg twice a day. After 7 days he was referred to our tertiary hospital for additional specialized diagnostic and therapeutic evaluations. On physical examination, there was a clear left eye proptosis and blindness, with absent direct photomotor reflex and preserved consensual reflex, impairment of left oculomotor, trochlear and abducent nerves, determining complete ophthalmoplegia, left peripheral facial palsy, complete hearing loss on the left and partial hearing on the right.
Considering the severity of the case, the high risk of infectious spread to the brain parenchyma and meninges and the microbiological profile of the hospital, it was opted to switch the antibiotic therapy to meropenem 2 g intravenous infusion every 8 h and vancomycin 1 g intravenous infusion twice a day.
Initial computed tomography (CT) of the head showed erosion of the anterior wall of the left external ear conduct and of the left mandible condyle and dehiscence of the external auditory canal, without other bone changes. (Fig. 3). Besides, there was a bilateral veiling of the mastoid air cells, more pronounced on the left. The magnetic resonance image (MRI) of the brain revealed a tissue occupying the left superior orbital fissure intraconal fat, with invasion of the left orbit, determining nerve compression (Figs. 4 and 5 ). There was involvement of the left optic, oculomotor, trochlear and abducent nerves, enhancement of the extrinsic ocular muscles and proptosis. Superior ophthalmic veins were preserved bilaterally and there was no evidence of cavernous sinus thrombosis. There was also heterogeneity of the whole sphenoid bone with hyperintensity on T2/FLAIR images and contrast enhancement (Figs. 4 and 5), tissue thickening and enhancement around the left temporo-mandibular articulation, besides contrast enhancement on the trajectory of the left facial nerve.
Ten days after initiation of antibiotics (7 days of oral ciprofloxacin and 3 days of meropenem and vancomycin), the patient underwent left canal wall-up mastoidectomy, with removal of tissue samples for microbiological evaluation, including Mycobacterium tuberculosis and fungus. During the surgical procedure, the mastoid cavity was cleaned, an integral ossicular chain was observed, as well as the tympanic membrane and disease-free middle ear. It was also opted for the insertion of ear ventilation tube bilaterally. The external ear canal skin fragments revealed mixed inflammatory infiltrate content with necrosis areas and multinucleated giant cells; the mastoid bone material showed chronic inflammatory infiltrate content. All microbiological tests performed were negative, and this was interpreted as a possible consequence of the early use of antibiotics.
The patient had no surgical complications, presented good recover of the right ear hearing capacity after 2 days, but showed no improvements of the neurological deficits nor the left ear hearing function, probably because of the chronicity of the case. Due to clinical stability and normal laboratory parameters, after 7 days of the surgical procedure the antibiotic therapy was switched to ciprofloxacin 400 mg intravenous infusion twice a day with a further objective of oral domiciliar ciprofloxacin, in order to totalize 6 week treatment period. Unfortunately, we have been facing dramatic months of COVID-19 pandemic, causing great apprehension specially over the hospitalized patients. Although the patient in case was not in the COVID-19 hospital section, on the 14th day of hospitalization, he initiated fever, dry cough and evolved after 2 days with dyspnea, motivating oral intubation and transfer to COVID-19 intensive care unit. The reverse transcription polymerase chain reaction (RT-PCR) confirmed Sars-CoV-2 infection. As an elderly man, with poorly controlled diabetes and in current malignant external otitis treatment, the patient had a poor outcome on this new coronavirus infection and sadly passed away after 10 days. This reflects the actual reality of the world and the difficulty of managing hospitalized patients during this COVID-19 pandemic. | diabetes mellitus, malignant external otitis, multiple cranial neuropathy, ophthalmoplegia, osteomyelitis | Not supported with pagination yet | null |
PMC5121158_01 | Male | 64 | A 64 year-old-man was referred to the hospital because of dry cough since 2 weeks. The patient was an ex-smoker, smoking 2 packs per day for 40 years. His medical history revealed hypertension treated with anti-hypertensive agents. The patient was conscious and alert, with body temperature 36.5 C, heart rate 122 bpm, and blood pressure 147/88 mmHg. Oxygen saturation was 93% in room air. Coarse crackles were detected bilaterally on chest auscultation. He had felt multiple arthralgias on the limbs symmetrically without swelling or deformation. Chest X-ray showed infiltration of the both lung fields (Fig. 1a). Chest computed tomography revealed the non-segmental patchy shadow and consolidation on both sides (Fig. 1b). The white blood cell count was 17,500 cells/muL and C-reactive protein level was 26.5 mg/dL. The patient was diagnosed with community-acquired pneumonia, and was subsequently treated with ampicillin/sulbactam and pazufloxacin. Blood and sputum cultures were negative, whereas anti-cyclic citrullinated peptide antibody (anti-CCP Ab) was elevated significantly. Antibiotic treatment was ineffective. Bronchoscopy, performed for more thorough examination, revealed white and soft tissues scattered in the trachea that could not be removed by suction or forceps (Fig. 2a). Purulent sputum was absent. Pathological and bacteriological evaluation of the tracheal lesions and lung was performed. Specimens of tracheal mucosa revealed findings consistent with NTB indicated by necrotic tissue with squamous metaplasia and inflammatory cells of tracheal tissue (Fig. 2b). However, the findings did not confirm chondritis. No specific pathogen was identified with PAS or Grocott and Ziehl-Neelsen staining. Lung biopsy indicated organizing pneumonia (OP), whereas eosinophilic leukocytosis and vasculitis were not observed. The patient was diagnosed with NTB and OP. Moreover, diagnosis of RA was determined results of rheumatoid factor and anti-CCP Ab tests, and evaluation of joints' manifestations by orthopedist. After the bronchoscopy, an acute exacerbation of the respiratory condition developed. Immediately, steroid pulse therapy and oxygen therapy were started. Then the both clinical condition were gotten stability. Repeat bronchoscopy to observe the tracheal lesion indicated resolution of scattered lesions without scarring; while, re-biopsy samples of trachea showed persistent necrosis. Subsequent, chest radiography indicated improvement (Fig. 3a and b). | bronchoscopy, necrotizing tracheobronchitis, rheumatoid arthritis | Not supported with pagination yet | null |
PMC9979078_01 | Female | 76 | A 76-year-old woman from Veracruz, Mexico, was referred to the ophthalmology clinic for progressive pain and scleral thinning in the right eye (RE). Two months before, an episode of diffuse anterior scleritis was successfully managed with non-steroidal anti-inflammatory drugs (NSAIDs). The patient had bare-sclera pterygium surgery with adjunctive beta-irradiation therapy twelve years ago in the same eye. The past medical history was remarkable for uncontrolled diabetes mellitus (DM; HbA1c=14%). The review of systems was negative for fever, weight loss, and chronic cough. The best-corrected visual acuity was counting fingers at 3 feet in the RE and 20/25 in the left eye. Slit-lamp evaluation of the RE revealed marked ciliary injection, a nasal corneal leucoma, and scleral necrosis at the pterygium excision site (Figure 1A (Fig. 1)). Fundus examination of both eyes showed diffusely scattered microaneurysms and haemorrhages corresponding to a moderate non-proliferative diabetic retinopathy. The fellow eye examination was unremarkable. A work-up was negative for RF, anti-CCP, ANAs, ANCAs against PR3 and MPO. The infectious test included a negative FTA-Abs and a PPD test (8 mm induration; see for a detailed classification of tuberculin skin reactions). Of notice, the patient had the BCG vaccination scar in her right arm. Topical treatment included loteprednol etabonate 0.5% every three hours, besifloxacin 0.6% QID, and aggressive lubrication. Systemic anti-inflammatory therapy consisted of 60 mg of oral prednisone daily, and 15 mg of weekly subcutaneous methotrexate (MTX) combined with an insulin regimen. After one month of therapy, the scleral necrosis progressed, and inflammatory activity was observed at the nasal peripheral cornea (Figure 1B (Fig. 1)). At this point, refractory SISN with peripheral corneal involvement was suspected, and thus, subcutaneous MTX was increased to 25 mg/week, and 1 g of intravenous methylprednisolone was prescribed for three days (Figure 1B (Fig. 1)). Moreover, empirical management with natamycin 5% QID and oral valaciclovir (1 g TID) for fungal and herpetic coverage was initiated. Unfortunately, the scleral necrosis continued progressing (Figure 2A (Fig. 2)); thus, a scleral biopsy, debridement, and a corneal tectonic graft with conjunctival autograft were performed due to impending corneal perforation (Figure 2B (Fig. 2)). Because of severe scleral thinning and a high risk of perforation, tissue sample was insufficient for culture analysis. Smear results, however, came out negative for bacteria, fungi, and mycobacteria. Polymerase chain reaction (PCR) analysis could not be performed due to a lack of insurance coverage. Pathology and smear results of the scarce necrotic tissue came out negative for bacteria, fungi, and mycobacteria. Because of a high risk of perforation, no other tissue was available for histopathologic study. One month later, the corneal tectonic graft lysed completely (Figure 2C (Fig. 2)). At this point, anti-tumor necrosis factor (anti-TNF)-alpha biologic therapy was considered; hence, an interferon-gamma release assay (IGRA) was ordered, resulting positive [Quanti-FERON -TB Gold In-Tube (QFT-GIT) TB1 antigen=1.11 UI/ml]. The chest X-ray, CT-scan, and bronchoalveolar lavage were negative for tubercular disease. Assuming a relationship of the scleral necrosis with active TB infection, antitubercular therapy (ATT) was initiated with a regimen of isoniazid 300 mg, pyrazinamide 1500 mg, ethambutol 1200 mg, and rifampicin 600 mg. The patient continued with topical steroids and antibiotics and a slow taper of oral prednisone for the next two months. The scleral necrosis subsided after one month of treatment. Her fasting glucose level was 117 mg/dl with a regimen of 850 mg daily metformin and 35 U of glargine insulin. An intensive 6-month regimen of ATT with four drugs was planned to reduce isoniazid and rifampicin for the next 6 months. The patient is currently in her seventh month of treatment and an excellent therapeutic response with no pain and no further scleral inflammation or necrosis are observed (Figure 3 (Fig. 3)). | antitubercular therapy, infectious scleritis, necrotizing scleritis, ocular tuberculosis, pterygium surgery, scleral inflammation, surgically induced scleral necrosis | Not supported with pagination yet | null |
PMC10308008_01 | Male | 55 | A 55-year-old male patient was admitted to the hospital with complaints of fever, cough, chest tightness, and paroxysmal palpitations for 1 week. He had a history of TB infection of the lungs 2 years ago. He received routine first-line anti-TB therapy for over 8 months (including isoniazid, rifampin, ethambutol, and pyrazinamide) and was discharged.
At admission, the patient has discontinued anti-TB treatment and was not taking any medication, including hormone preparations, to control other chronic diseases. Additionally, he denied a history of diabetes, hypertension, or tumors. Notably, he reported several sudden chest pain episodes lasting for a few seconds, accompanied by dizziness and amaurosis during the past week. He underwent a general clinical examination at a local outpatient community hospital setting. Previous medical records showed temporary sinus bradycardia with premature atrial beats on electrocardiogram (ECG) (Figure 1A), which spontaneously recovered to a normal rhythm after rest.
Based on physical examination at admission, he had a height of 169 cm, body mass index of 18.13 kg/m2, temperature of 36.9 C, respiration rate of 18 breaths/min, blood pressure of 109/64 mmHg, and mild malnutrition. No anemia or palpable superficial node enlargement were detected. ECG showed a type II second-degree sinoatrial block (Figure 1B). However, the patient had no specific symptoms other than mild palpitations and chest tightness; therefore, an atropine challenge test was not performed. Lung auscultation revealed scattered pulmonary rhonchi and mild rales in both lungs. Chest radiography revealed fibrotic tuberculous lesions without acute processes. Blood biochemical tests revealed a white blood cell count of 8.06 x 109/L, polymorphonuclear neutrophils level of 96.2%, and high-sensitivity C-reactive protein level of 106.0 mg/L, indicating the presence of infection or inflammation. Other biochemical tests revealed a creatine kinase (CK) level of 109 IU/L, CK-MB level of 16 IU/L, and cardiac troponin I level of 0.02 ng/ml. In addition, serological tests for Hepatitis B, syphilis, and HIV were negative.
Given that the condition of the patient was stable, the emergency physician initially diagnosed the patient with recurrent TB or cardiovascular diseases and prescribed over-the-counter remedies, including dextromethorphan hydrobromide and traditional cough syrup, to relieve cough and reduce sputum and recommended that the patient visits the Specialty Hospital of Infectious Diseases the following day for a further comprehensive examination of the lungs and heart. Unfortunately, after returning home, the patient suddenly experienced severe chest pain, dyspnea, and cardiac arrest at midnight and died after unsuccessful resuscitation attempts. Following the request of the patient's family and the law of China, the body was delivered for a forensic autopsy to examine the cause of the unexpected death.
The autopsy revealed that the epicardium of the right auricle and right atrium were studded with slightly off-white tubercles (Figure 2A). The cut surface of the myocardium showed irregular gray-white lesions on the ventricular wall (Figure 2B). The main trunk of the left coronary artery showed the presence of atheromatous plaques with lumen stenosis (<25%). All other branches of the coronary artery were normal, and there was no evidence of pleural or pericardial involvement. Multiple white nodules, 1-2 mm in diameter, were observed with partial calcification in cut sections of the lungs. The hilar lymph nodes were grayish-white in color and enlarged. No significant abnormalities were observed in any other organ. Histological examination of the sinus node region revealed granulomas, focal fibrosis, and fatty infiltration (Figure 2C). The myocardium also showed a broad context of fibrosis with infiltrated lymphocytes, many Langhans giant cells, and caseating epithelioid granulomas (Figure 2D). Although acid-fast bacillus was not detected in the myocardium, tubercle bacillus deoxyribonucleic acid (DNA) was confirmed by real-time polymerase chain reaction (PCR) on formalin-fixed lung tissue. Tubercle bacilli were detected in the granulomatous areas of the lung tissue using Ziehl-Neelsen (ZN) staining (Figure 3). | mycobacterium tuberculosis, myocardial tuberculosis, pulmonary tuberculosis, sinus node, tuberculous myocarditis | Not supported with pagination yet | null |
PMC7161110_01 | Male | 29 | A 29-year-old male presented at the Allergy Clinic (Allergy and Clinical Immunology Unit, Public Central Teaching Hospital in Warsaw) due to an episode of itching and burning in the mouth, tongue swelling, difficulty swallowing, feeling of anxiety, and rapid pulse, all of which developed several days earlier, within 5 min after ingesting teff flakes. Since the patient had been previously provided with an emergency kit, he immediately took 30 mg prednisone and 30 mg cetirizine orally. As his general condition improved rapidly, there was no need for adrenalin administration. The patient did not report to his doctor directly following the incident. The patient had already had a history of similar symptoms in the form of burning and itching in the mouth, albeit less severe, following ingestion of gluten-free bread from teff flour or containing teff. 8 months ago, in outpatient setting we diagnosed this patient with inhalant allergy to milk thistle. Four years prior to his presentation at our clinic, the patient started working at a production facility that manufactures healthy, organic foods, including gluten-free flours, food additives, and natural dietary supplements. During the first year of his employment there, he worked at a packaging station for dry, finely-ground fruit of milk thistle. At that time, he experienced no health issues. For the last 3 years, the patient has held an executive position and had no direct exposure to the packaging premises. However, he reported about a year's history of rhinorrhea, sneezing, burning watery eyes, and wheezing whenever he came in contact with even minute amounts of milk thistle. The patient denied ever having consumed milk thistle in the form of infusions, teas, food additives, or pharmaceutical form (tablet) excipients. Milk thistle fruit is delivered to the plant already in a dry, finely ground form, which is not further processed, but only packaged on the premises. Milk thistle is delivered from an organic food farm in a defatted, ground form. The product has an appropriate quality certificate. For approximately 1 year the facility has been importing teff cereal from the Netherlands and manufacturing gluten-free flours and flakes. The facility has a product-quality certificate, containing information on the product's sensory properties, storage conditions, physicochemical requirements, nutritional value, and allergens. The patient has not been diagnosed with celiac disease nor is on any special diet. However, as a co-owner of the facility, he samples all the foods products manufactured on the premises. It was during such routine sampling of teff-flour bread and flakes that the patient first noticed the symptoms listed above.
Past medical history revealed no major health issues and no current medication. His family history was negative for allergies. The patient denied hypertension, coronary artery disease, diabetes mellitus, and peptic ulcer disease. He reported periodic burning sensation in his mouth, heartburn, and dysphagia following ingestion of certain raw fruit and vegetables (apples, pears, plums, carrots, celery root). The patient had been stung twice by a wasp and developed considerable local reaction which, however, required no medical intervention. Nonetheless, 2 years prior to presentation, a wasp sting produced chest tightness and wheezing as well as localized edema and erythema. At that time, the patient was examined at an emergency room; however, he no longer has any medical records from the incident nor remembers what kind of treatment he received.
Physical examination revealed no apparent abnormalities. Otorhinolaryngological examination findings were as follows: Nose:no nasal septum deviation; pink, moist mucosa, slight hypertrophy of the inferior turbinates; no polyps or other growths; Pharynx:a normal tongue, with no coating; symmetrical palatal arches; palatal tonsils present in their anatomical location, no pathological discharge; clear posterior pharyngeal wall; Ears:bilateral otoscopy revealed no abnormalities; Larynx:normal appearance and function. Auscultation revealed normal breath sounds over both lung fields, no murmurs, and a regular heartbeat. The abdomen was soft, nontender. The skin was clear, with no evidence of exanthema.
Allergy diagnostics. Spirometry results were normal (FEV1 117% (5.14 L); FEV1/FVC 97%, 34th percentile, SR-0.42); rhinomanometry results were within normal limits. Skin prick testing (SPT) and skin tests with native alimentary allergens (from the foods brought by the patient) revealed high reactivity to the allergens of milk thistle (16/35) and teff flour (22/60), with the negative control score of 0/0, and histamine score of 3/5. Skin tests with Allergopharma allergens, sIgE (Table 1), and Faber test (Table 2) were also conducted. In order to verify the results of skin tests with native food allergens, the same tests with teff allergens were performed in 5 healthy volunteers and 5 volunteers diagnosed with an inhalant allergy to grasses, yielding negative results. Skin tests with native milk thistle allergens were also conducted in 5 healthy volunteers, yielding negative results.
Due to the presence of upper gastrointestinal (GI) symptoms (heartburn, acid regurgitation, foul taste in the mouth), the patient was referred to the Gastroenterology Department at Medical University of Warsaw to undergo diagnostic assessments for eosinophilic esophagitis. At the Gastroenterology Department the patient underwent gastroscopy with esophageal and gastric biopsy. Neither the gastroscopy nor microscopic examination of the biopsy samples revealed any upper GI tract abnormalities. Eosinophilic esophagitis was excluded. Since Helicobacter pylorii was detected, appropriate treatment was administered (500 mg metronidazole 3 times a day, 500 mg tetracycline 4 times a day, 120 mg bismuth oxide 4 times a day, 40 mg pantoprazoleonce a day). Following the course of treatment, the patient's GI symptoms resolved completely. Currently, the patient remains under observation in an outpatient setting (at our clinic). The patient was recommended to carefully avoid any future contact with teff flour and milk thistle. Additionally, the patient received an emergency kit containing three 10-mg prednisone tablets, three cetirizine tablets, and a pre-filled syringe with adrenalin (EpiPen Senior). Moreover, the patient received thorough training on how and when to use the drugs from his emergency kit. Due to the patient's diagnosis of wasp venom allergy (based on his medical history and serum specific IgE test results), he was also qualified to undergo venom immunotherapy (VIT), with the treatment scheduled to begin in September 2019. | allergen, allergies, eragrostis tef, milk thistle, silybum marianum, teff | Not supported with pagination yet | null |
PMC9720115_01 | Male | 9 | A 9-year-old boy with intermittent fever for 2 months was transferred to our hospital on November 3, 2021. He was born with alpha thalassemia (-SEA/alphaalpha), and from his birth to 2018, he had received five red blood cell transfusions. He has been Bacilli Calmette-Guerin (BCG) vaccinated at birth under the national vaccination program. He has no recent travel history, and his parents reported no family hereditary diseases, besides thalassemia, no TB history nor TB exposure.
The patient started to develop intermittent fever in August 2021, with the highest body temperature of 38.0 C and night sweats. There were no respiratory symptoms or weight loss. He was admitted to a local children hospital shortly after his fever had persisted for 5 days. His routine blood test on admission showed white blood cell (WBC) 2.6 x 109/L, neutrophils (Neu) 1.15 x 109/L, hemoglobin (Hb) 74 g/L, and platelets (PLT) 211 x 109/L. Ultrasound scan revealed bilateral cervical lymphadenopathy and an enlarged spleen.
In 3 days, his hemoglobin level dropped to 64 g/L, and he was given 2U red blood cell infusion. Repeated blood test on the following day showed decreased level of WBC to 1.5 x 109/L and Neu of 0.51 x 109/L with an elevated Hb level of 90 g/L and an unremarkable change of PLT 201 x 109/L. Viral markers for Epstein-Barr virus (EB DNA) was negative. In addition, subsequent blood interferon-gamma release assays (IGRAs) and skin purified protein derivative (PPD) tests were positive. Lung computed tomography (CT) showed calcification of the right hilum and mediastinal lymph nodes. In the absence of lung infiltration and tuberculous foci, latent tuberculosis infection (LTBI) was suspected. A bone marrow aspiration smear performed the following day showed active bone marrow hyperplasia, significantly decreased neutrophil level, and generally normal morphology. The patient had persistent daily fever between 37.4 C and 38.8 C accompanied with dry cough, fatigue, and loss of appetite. He was empirically administered with amoxicillin 0.25 g three times a day for 3 days and antifebrile for a week. But his fever remained unsolved during the treatment, fluctuating in the same range as before. Pathological findings from his cervical lymph node biopsy showed no caseous necrosis and no acid-fast mycobacteria. The persistent low WBC in peripheral blood had raised concern. To look into possible causes of the persistent fever, a second bone marrow puncture was performed. Bone marrow smear was positive for acid-fast staining (Figure 1). Disseminated TB infection was suspected. But further sputum and cerebrospinal fluid smear were negative for both acid-fast staining and TB-DNA (CapitalBio Technology, China). Thus, pulmonary TB and tuberculous meningitis were ruled out. The bone marrow was presumed as the tuberculous origin. Anti-TB regimen composing isoniazid, rifampicin, pyrazinamide, and ethambutol was initiated from the diagnosis. His temperature resumed to normal range 4 days later. His appetite also improved.
But a week later, he had fever again with the highest measure of 40.0 C. Serum ferritin was observed to have elevated to 3,603.35 ng/ml (reference: < 300 ng/ml). Methylprednisolone 1 mg/kg q12 h was administered as anti-inflammatory therapy, but his fever did not go away. A repeated bone marrow aspiration was performed the following day to investigate the causes for the unresolved fever, elevated serum ferritin, and decreased WBC. Bone marrow biopsy showed active hyperplasia with occasional hemophagocytic histiocytes, mainly phagocytizing white blood cells, red blood cells, and platelets (Figure 2). Bone marrow for real-time PCR (qPCR) assay for TB was positive; moreover, gene sequencing revealed the promotor region of InhA gene mutation (-15C > T), which caused resistance to isoniazid. Bone marrow for TB culture was performed but had finally turned out negative. Serum ferritin was precisely monitored and was found to further elevated to 9612.81 ng/ml in 5 days. HPS was confirmed, and 10 mg/kg of methylprednisolone was prescribed daily. In 2 days, the patient's fever resolved. Serum ferritin dropped to 5,755.54 ng/ml and WBC in peripheral blood was restored to a normal level. Whole-genome sequencing confirmed no variants of exon. This test result rule out the known primary genetic causes of HLH. Diagnosis was confirmed as having (1) bone marrow TB with isoniazid resistance; (2) secondary HPS.
Before administration of isoniazid-resistant TB regimen modification, the patient developed nausea, loss of appetite without fever 18 days after initial anti-TB regimen. Systematic examination revealed yellow skin and sclera with hepatosplenomegaly. Liver function test showed total bilirubin (TBIL) of 111.1 mumol/L, directed bilirubin (DBIL) 67.3 mumol/L, alanine transaminase (ALT) 520.5 U/L, and aspartate transaminase (AST) 321.5 U/L, which were consistent with drug-induced liver injury (DILI). He was transferred to our hospital for specialized tuberculosis management where his regimen was reviewed and modified to the following: linezolid 300 mg/day, ethambutol 0.5 g/day, and levofloxacin 0.25 g/day based on his body weight of 25 kg. Methylprednisolone was reduced to 2 mg/kg/q8h. As serum ferritin was gradually decreasing and his body temperature and WBC were normal, methylprednisolone was lowered to 0.4 mg/kg/q12h 12 days later.
After 15 days of the above therapy, a follow-up evaluation of bone marrow aspirate for metagenomic next-generation sequencing (mNGS) and qPCR assay showed no detection of M. tuberculosis. Subsequent laboratory investigations confirmed normal liver function and a lowered serum ferritin level of 1,150.0 ng/ml. A 0.3-g rifapentine was added twice a week to his anti-TB regimen. He was discharged with the prescribed methylprednisolone at a tapering dose of 4 mg every 10 days (Figure 3) until the next follow-up consultation. He is being followed up in our outpatient unit for the next 2 years for this rare medical condition. The child has no more fever, but his hepatosplenomegaly persisted. He has returned to school and is leading a normal life. As of press time, the patient's anti-TB treatment is still ongoing. | bone marrow tuberculosis, child, hemophagocytic syndrome, isoniazid-resistant, tuberculosis | Not supported with pagination yet | null |
PMC6446437_01 | Male | 44 | A 44-year-old Caucasian man presented to an outpatient clinic with a 2-month history of fatigue, night sweats, weight loss, loss of appetite, and mild abdominal discomfort. The patient did not have fever, chills, cough, nausea, vomiting, itching, urinary, or bowel symptoms. The patient had a past medical history significant for biopsy-proven sarcoidosis of the mediastinal lymph nodes, which was diagnosed 9 years prior. At that time, the patient had hilar lymphadenopathy seen on a routine chest radiography. The disease seemed inactive, as the patient never had symptoms related to sarcoidosis nor received treatment throughout the years. He also had a history of hypertension, hyperlipidemia, bipolar disorder, coronary artery disease with percutaneous coronary intervention performed a month prior to the current presentation, as well as a recently diagnosed type 2 diabetes mellitus. His regular home medications included amlodipine, metoprolol tartrate, lisinopril, lamotrigine, clopidogrel, metformin, rosuvastatin, and sildenafil. The patient denied any history of alcohol or tobacco use and stated that he used to work as a secretary.
On physical examination, the vital signs were normal. Body mass index was 37.2 kg/m2, and weight was 263 pounds. The general, lung, heart, and abdominal examinations were unremarkable, and no palpable lymphadenopathy was identified. A battery of laboratory tests were performed and revealed the following: alanine aminotransferase and aspartate aminotransferase levels were within normal limits; however, the alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were elevated (ALP = 258 U/L, reference = 38-126 U/L; GGT = 274 U/L, reference = 12-73 U/L). He was also found to have hyperbilirubinemia (total bilirubin was 1.7 mg/dL, reference = 0.0-1.3 mg/dL, and direct bilirubin was 0.7 mg/dL, reference = 0.0-0.3 mg/dL). The total protein, albumin, serum creatinine, and calcium levels were within normal limits. Further workup including ceruloplasmin, serum iron saturation, lactate dehydrogenase, serum angiotensin converting enzyme level, and erythrocyte sedimentation rate were normal. Alpha-1 antitrypsin antigen, a viral hepatitis panel, and anti-mitochondrial and anti-smooth muscle antibodies were negative. A slight elevation in beta2-microglobulin levels were noted (3.2 mg/L, reference = 0.8-2.34 mg/L).
Ultrasound examination of the abdomen was negative for common bile duct dilatation but showed a 3.5 x 4.1 cm abdominal mass at the head of pancreas. Computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast demonstrated cirrhotic appearance of the liver with steatosis, with enhancing hepatic masses, splenomegaly, and multiple enlarged lymph nodes in the periaortic and portocaval areas. The largest lymph node was measured at 7.2 x 4.3 cm in diameter in the precaval area. There was, however, no visible pancreatic lesions, biliary duct dilatation, or gallbladder stones (Figure 1).
Histopathological examination of a transjugular liver biopsy showed expanded portal areas containing occasional granulomas with the majority of the granulomas appear non-necrotizing, with a few demonstrating central necrosis. Mild macrovascular steatosis and chronic inflammation is noted (Figure 2). Auramine-rhodamine and GMS stains was negative for acid-fast bacilli and fungal organisms. Staining for iron and immunoglobulin G4 was negative.
Evaluation for other etiologies of abdominal lymphadenopathy was performed to exclude malignancies and infectious granulomatous diseases. Infectious workup for granulomatous hepatitis was negative for Histoplasma, Bartonella, tuberculosis, and Coxiella burnetii (Q fever). An autoimmune workup including ANA, ANCA, immunoglobulin G4, complement C3, and complement C4 levels was performed and was unremarkable.
A provisional diagnosis of hepatic sarcoidosis and nonalcoholic steatohepatitis was procured based on the biopsy results. Unfortunately, at that time the patient refused steroid treatment as well as immunosuppressive therapy; however, he agreed to ursodeoxycholic acid 1500 mg daily to help with itching.
Two months later, the patient started to complain of excruciating pain in his lower back with radiation to his thighs and legs, in addition to diffuse joint pain. His loss of appetite and fatigue did not improve significantly, and he continued to lose weight. A whole body positron emission tomography-CT scan showed extensive hepatic uptake, hypermetabolic lymphadenopathy involving the chest, cervical, supraclavicular regions, upper abdominal, retroperitoneal, iliac chain, and inguinal lymph nodes, as well as numerous fluorodeoxyglucose-avid osseous lesions involving the thoracic and lumbar spine, left proximal humerus, left scapula, pelvis, and proximal right femur. There was a concern of metastatic bone disease given the widespread distribution of the lesions (Figure 3). Evaluation with spine, pelvis, and upper extremity, magnetic resonance imaging (MRI) showed multiple small marrow lesions involving the vertebral bodies in the thoracic and lumbar spine, with small spotty lesions noted in the sacrum, pelvis, hips, ribs, and humerus on the left. MRI of the brain showed no evidence of neurosarcoidosis. An ophthalmologist evaluated the patient, and ocular involvement was ruled out. The patient underwent a bone biopsy of the T12 vertebra, which revealed benign trabecular bone with replacement of the marrow space with numerous non-necrotizing granulomas and fibrosis consistent with diagnosis of vertebral sarcoidosis (Figure 4).
Of note, while this extensive workup was taking place, the patient developed a sudden onset of left flank pain and hematuria. There was a small left ureteric stone on abdominal imaging identified. He underwent laser lithotripsy and left ureteral stent placement.
The patient agreed to immunosuppression and was started on methotrexate 20 mg subcutaneously once weekly, folic acid 1 mg daily, and prednisone 5 mg daily as treatment for systemic sarcoidosis. However, 2 months later, he developed actinomycosis skin infection of the groin. Methotrexate was held, and he was treated with amoxicillin until the infection resolved. The patient was restarted on methotrexate. Two months after restarting methotrexate, the patient reported significant clinical improvement of his pain, loss of appetite, and has gained 40 pounds since the start of methotrexate. His liver enzymes improved significantly. A repeat positron emission tomography-CT scan demonstrated a decrease in the lymph nodes, bone, and hepatic lesions size. | bone sarcoidosis, granulomatous disease, hepatic sarcoidosis, sarcoidosis, systemic sarcoidosis | Not supported with pagination yet | null |
PMC9095931_01 | Female | 41 | A 41-year-old female was admitted to the Department of Endocrinology at our medical center for the following concerns: "the menstrual cycle is prolonged for half a year, and fatigue, palpitations, and shortness of breath for 2 months". The patient reported a 2-year history of 10-min to 1-h abdominal pain and bloating episodes that were spontaneously resolved without treatment, and she had not been treated for the above symptoms. The physical examination revealed a flat abdomen, no tenderness or rebound tenderness in the abdomen, and bowel sounds present five times/min. The laboratory test results showed the following: a white blood cell count of 12.81*109/l, a red blood cell count of 2.98*1012/l, a hemoglobin level of 48 g/l, and a C-reactive protein level of 9 mg/l. The gynecological ultrasound revealed a cervical cyst. The abdominal ultrasound showed that the patient had a fatty liver and a liver cyst. The patient had no history of abdominal surgery, inflammatory bowel disease, tuberculosis, or long-term medication use.
Iron and 4 U red blood cells were given symptomatically after admission to address the patient's severe anemia. On the morning of the 4th day of admission, the patient's condition changed, and she experienced sudden, severe, and intolerable abdominal pain after defecating. An emergency abdominal CT scan showed intestinal obstruction, possibly caused by the torsion of adhesions (Figure 1). Physical examination of the patient revealed abdominal distension, abdominal muscle tension, whole abdominal tenderness, rebound tenderness, and bowel sounds four times/ min.
Emergency surgery to relieve the intestinal obstruction symptoms was performed after a discussion with the patient and family members. First, exploratory laparoscopic surgery was performed, and we observed that the small intestine and colon were conglutinated and twisted into a mass surrounded by a fibrous membrane (Figure 2). It was difficult to separate the adhesions under laparoscopy; thus, the decision to convert to open surgery was made, and the mid-abdomen was cut to allow access to the abdominal cavity. After separating the adhesions and freeing the bowel, a small intestine obstruction was found approximately 80 cm from the ligament of Treves, and an enteroenteric fistula was observed between the jejunum, ileum, and sigmoid colon (Figure 3).
Due to the obvious edema of the intestinal canal in the abdominal cavity, the enteroenteric fistula was relatively stable, and the patient had not undergone bowel preparation before surgery, after a detailed discussion about the surgical approach, we decided to focus on relieving the obstruction during the surgery to reduce the risk for postoperative anastomotic fistula and abdominal infection. The subsequent treatment of the jejuno-ileo-colonic fistula would be determined based on the patient's recovery and medical review. Ultimately, we successfully relieved the intestinal obstruction, performed adhesiolysis, and oriented the small bowel to its normal position. The intraoperative bleeding volume was approximately 50 ml, and 2 U of red blood cells and 200 ml of plasma were administered.
Anti-infection medication, gastrointestinal decompression treatment, antiacids, nutritional support, and iron supplementation were provided as symptomatic treatments after surgery. On the third postoperative day, the patient presented with anal exhaust and was able to consume water. On the fifth postoperative day, the patient defecated and began a complete liquid diet; on the same day, her laboratory test results showed a white blood cell count of 13.64*109/l, a red blood cell count of 3.62*1012/l, and a hemoglobin level of 76 g/l. On the sixth postoperative day, the patient and her family expressed a strong desire to transfer to a local hospital closer to the patient's home for easier care. After we fully assessed the patient's condition and provided detailed information about the risks, the following future treatment plan was issued: gradually return to a normal diet and continue anti-infection and nutritional support treatment, and undergo dilatation and curettage on the first day of menstruation to explore the causes of the prolonged menstrual cycle. Finally, the patient was discharged from our hospital on the 6th postoperative. Then, after another 11 days of conservative treatment, she recovered and was discharged from Feicheng People's Hospital. We followed up with the patient by telephone. She reported a white blood cell count of 8*109/l, and a hemoglobin level of 181 g/l on March 4, 2022 and she resumed a normal diet and daily exercise activities. | abdominal cocoon, case report, enteroenteric fistula, jejuno-ileo-colonic fistula, treatment | Not supported with pagination yet | null |
PMC9752143_01 | Female | 7 | A 7-year-old girl (III-1 in Figure 1A) with jaundice, a firstborn female of healthy parents (Korean male and Vietnamese female) at 39 weeks of gestation, visited the Division of Endocrinology, Department of Pediatrics, Jeonbuk National University Hospital (Jeonju, South Korea), for evaluation of a persistent hemolytic anemia. The proband appeared chronically ill with yellowish skin color, icteric sclera, hepatomegaly, and splenomegaly on physical examination. The rest of the examination was unremarkable. She was born at 38 weeks by vaginal delivery, with a birth weight of 2,300 g and unremarkable perinatal history. She was admitted to the neonatal intensive care unit after birth due to a lethargic condition. She was diagnosed with fetomaternal transfusion with suspected HHA. She was transfused with packed red cells. As time went on, she became pale and bright yellowish skin discoloration progressively. There was no family history of hemolytic disease. On the date of birth, her initial investigations showed a hemoglobin level of 5.3 g/dl, mean cell volume of 122.7 fl, total leukocyte count of 29,780/mm3, platelets of 159,000/mm3, and reticulocyte percentage of 60.18%. Direct Coombs test result was positive. A peripheral blood smear test showed marked leucoerythroblastic reaction and atypical lymphoid cells (1%-2%). Total bilirubin level was 12.51 mg/dl (normal range, 0.2-1.2 mg/dl), of which direct bilirubin level was 0.94 mg/dl (normal range, 0-0.4 mg/dl). Her aspartate aminotransferase and alanine aminotransferase levels were 107 IU/l (normal range, 24-95 IU/l) and 22 IU/l (normal range, 6-40 IU/l), respectively. Based on signs and symptoms including mild to severe anemia, paleness, fatigue, yellow discoloration of skin (jaundice), and bone problems, thalassemia was suspected initially in the proband. Sanger sequencing for HBB and HBA1/2 was performed at the Green Cross Genome (Yongin, South Korea). As a result, heterozygous missense mutation (NM_000518.5: c.79G>A, p.Glu27Lys; rs33950507) of the HBB was detected in both the proband and her mother (II-2 in Figure 1A). Although her mother had the same heterozygous HBB gene mutation, she showed no hemolytic symptoms. Thus, the proband and her mother were diagnosed with beta thalassemia trait. This trait usually has no clinical manifestation. The proband has been receiving RBC transfusions 1-2 times a month since birth until recently. On the other hand, the reticulocyte count of the proband was 1.64% at the time of the PK activity measurement. The red cell count and hematocrit were 1.88 x 106/mul and 16.5%, respectively; thus, the absolute reticulocyte count was 30,832/mul and the approximate corrected reticulocyte count percent was 0.6%.
Because the proband's parents and other family members presented no clinical symptoms associated with HHA, genetic counseling and segregation analysis were additionally performed to identify other genetic causes besides the HBB gene. | pk enzyme activity, pklr exon deletion, copy number variation, multiplex ligation-dependent probe amplification, next-generation sequencing, pgly536asp, pyruvate kinase deficiency | Not supported with pagination yet | null |
PMC9597014_01 | Female | 60 | A 60-year-old White, non-Hispanic woman with history of bilateral lung transplant due to severe emphysema presented with painful occipital subcutaneous nodules and a painful right index finger 60 days post-transplant. Induction immunosuppression consisted of basiliximab and maintenance immunosuppression was prednisone, tacrolimus, and mycophenolate. Histologic examination of native lungs showed changes related to smoking (severe emphysema and bronchiolitis), bronchiectasis, and non-necrotizing granulomatous inflammation suggestive of hypersensitivity pneumonitis. Acid-fast bacilli (AFB) and Grocott Methenamine Silver (GMS) stains were negative for organisms. Two days after transplant, the right lung graft was removed due to lobar torsion and infarction. Histologic examination of explanted graft confirmed infarction and AFB stains were also negative. Patient was discharged home on post-operative day 13. Thirty days post-transplant she had declining pulmonary function tests and was treated for presumed rejection with high-dose methylprednisolone for 3 days and rituximab due to presence of donor-specific antibodies. She developed parainfluenza infection on post-transplant day 54 and received methylprednisolone and intravenous immunoglobulin. Sixty days post-transplant she developed painful nodes in the occipital area and painful swelling of the right index finger. Two weeks later, she presented to clinic and was started on linezolid and ceftriaxone for cellulitis. Shortly after completing a 2-week course of antibiotics, pain worsened and she developed nausea, vomiting, chills, and diaphoresis prompting hospital admission. Social history was notable for residing in Kansas, and never having lived or traveled outside the United States. She had dogs and cats but denied bites or scratches. She denied exposure to livestock or other animals, recent water exposures, remote traumatic injuries, gardening, or other outdoor work. She denied consumption of unpasteurized dairy products. She had no history of incarceration or homelessness.
On examination, she was afebrile and well-appearing. She had two exquisitely tender, non-mobile nodules in her occiput without overlying skin discoloration or drainage. There was no cervical, axillary, or inguinal lymphadenopathy. Her right index finger was edematous and erythematous, with limited range of motion. Right-sided breath sounds were absent and left lung was clear to auscultation. There was no abdominal tenderness, hepatosplenomegaly, or rash. Laboratory studies were notable for leukopenia with 3 x 109 cells/liter with lymphopenia of 0.6 x 109 cells/liter.
Non-contrasted chest computed tomography showed new, numerous hypoattenuating liver lesions. Abdominal magnetic resonance imaging (MRI) showed multiple rim-enhancing hepatic lesions suggestive of multifocal abscesses. Right-hand MRI showed a peripherally enhancing 1.3-cm fluid collection along the palmar aspect of the index finger associated with the flexor tendon sheath. Transthoracic echocardiogram and brain MRI were unremarkable. Extensive infectious work-up remained negative.
The patient underwent core needle biopsy of liver lesions and finger incision and drainage. Direct staining of finger tissue was positive with 1-9 acid fast bacilli (AFB)/10 high-power field and empiric treatment for disseminated non-tuberculous mycobacteria (NTM) with linezolid, cefoxitin, azithromycin, and moxifloxacin was promptly initiated. Both liver and tendon histopathology noted granulomatous inflammation with AFB (Figures 1 and 2). Finger and liver tissue cultures grew AFB after 4 days identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry as Mycobacterium tuberculosis complex. Antimicrobial susceptibility testing was performed, and isolate showed susceptibility to ethambutol, isoniazid, pyrazinamide, and rifampin. The patient was started on TB induction therapy with rifabutin (to avoid interaction between rifampin and tacrolimus), isoniazid, pyrazinamide, and ethambutol. AFB sputum, blood, and urine cultures remained negative after 8 weeks. Mycophenolate was held and prednisone and tacrolimus were continued. Patient received 2 months of 4-drug induction treatment followed by 10 months of rifabutin and isoniazid for a total of 12 months of treatment.
The organ donor was originally from Mexico and did not have known medical history. The cause of death was cerebral hemorrhage. There was no information available regarding prior TB testing or treatment. No other recipients have thus far developed TB. | lung transplant, mycobacterium infections, organ donation, tenosynovitis, tuberculosis, tuberculosis screening | Not supported with pagination yet | null |
PMC8225338_01 | Male | 61 | A 61-year-old male from Lucena City (located 134 km south of Manila), right-hand dominant with 20 pack-year smoking history, presented with a painful soft tissue lump on the posterolateral aspect of his left distal arm with no other accompanying symptoms, at our institution in Metro Manila in May 2020 when the entire island of Luzon was under a state of enhanced community quarantine (ECQ). Our institution then catered to both patients with and without COVID-19. The patient underwent core-needle biopsy at another hospital a month prior to consult, revealing fibrocollagenous tissue with nonspecific chronic inflammation on final histopathology. On physical examination, there were no neurological deficits, although Tinel's sign was positive. Review of left arm radiographs done at another hospital shows cortical erosion of the distal humerus with periosteal elevation (Figure 1a and b), while magnetic resonance imaging (MRI) confirmed a heterogeneously enhancing intramuscular mass involving the triceps measuring 3 cm x 4 cm x 4.5 cm (Figure 2a), associated with cortical destruction of, and abnormal marrow signals in the posterolateral humerus (Figure 2b), and partial tumoural encasement of the radial nerve (Figure 2c). Our differential diagnoses included benign and malignant primary soft tissue tumours, but upon review of chest radiographs done at another hospital, we noted finding of heterogenous ill-defined opacity in the right upper lobe that was officially read as tuberculosis (Figure 3). Although pulmonary tuberculosis was a possibility, we were then highly considering presence of sarcomatous metastasis in the lung. Financial constraints prevented further evaluation by chest computed tomography (CT).
During the ECQ, travel was restricted for most people, and many cities controlled their borders in an attempt to contain local transmission of COVID-19. The patient tested negative for COVID-19 by reverse transcriptase polymerase chain reaction (PCR) testing and therefore, requested to be admitted for continuation of care. But for fear of getting nosocomial SARS-CoV-2 infection, he pleaded for a short inpatient stay and an expedited hospital care. Citing early reports having found cancer patients especially vulnerable to SARS-CoV-2 infection, and cancer diagnosis a predictor of perioperative mortality, we agreed to forego performing preoperative biopsy. Imaging findings demonstrating aggressive biology and the possibility of pulmonary metastasis added up to a primary consideration of soft tissue sarcoma for our case. Thus, without benefit of a biopsy-proven diagnosis, our team decided to request for intraoperative frozen section to rule out malignancy, and prepare for wide tumour resection with frozen autograft reconstruction of the humerus. Without advantages of having an active cancer tumour board in the interim, we adopted recommendation by the French Sarcoma Group to pursue surgery even for high grade soft tissue sarcomas with distant metastasis in operable patients without COVID-19 symptoms.
The surgery was performed under general anaesthetic, with members of the surgical team additionally wearing Tyvek coveralls (DuPont ; Delaware, USA), N95 respirators (3M ; Minnesota, USA) and face masks. We approached the tumour posterolaterally (Figure 4a), with the patient on right lateral decubitus position. Prior to resection of the tumour, tumoural tissue was obtained and sent intraoperatively for histopathological analysis, revealing signs of malignancy by frozen section. We therefore ruled in soft tissue sarcoma, and decided to resect the tumour with wide margins. Upon dissection, radial nerve was adherent to tumour and cortical bone was visibly eroded (Figure 4b). Wide bone margins were identified by C-arm guidance, and humeral segment together with involved radial nerve was included in the resection (Figure 4c). Resected tumour-bearing bone was freed of tumoural tissues then soaked in liquid nitrogen (Figure 4d), thawed, washed with distilled water and re-applied to humerus by fixation using plates and screws (Figure 4e). The operation lasted 361 minutes from induction to skin closure with no intraoperative complications, and estimated blood loss was 300 mL. After the surgery, patient's left elbow was immobilised with arm sling, and postoperative arm radiographs showed stable humeral reconstruction with acceptable alignment (Figure 5a and b). We strategised to start physical therapy upon notice of bridging callus by radiographic surveillance, and patient was discharged well with unremarkable inpatient course.
Final histopathological findings of the operative sample, with immunohistochemistry study, concluded the diagnosis of metastasis of an adenocarcinoma of lung origin (Figure 6a and b). The resection margins were negative for tumoural involvement. Positron emission tomography scan was done, which showed a lobulated, calcified lung mass within the right apical segment measuring 2.4 cm x 1.9 cm x 3.2 cm, as well as two rim-enhancing nodules in both frontal lobes suggestive of brain metastases. Patient was then referred to medical and radiation oncology services for palliative treatment, and at the time of writing, has completed ten sessions of whole-brain radiation therapy at another hospital and is to start adjuvant pemetrexed (Alimta ; Eli Lilly and Co.; Indiana, USA) and carboplatin (Biovinate ; Unilab, Inc.; Mandaluyong City, PH) treatment. Physical therapy is also done regularly on outpatient basis. | covid-19, biopsy, frozen autograft reconstruction, lung cancer, sarcoma, skeletal muscle metastasis | Not supported with pagination yet | null |
PMC7784203_01 | Female | 43 | We present the case of a 43-year-old female presenting with secondary amenorrhea. Ten months prior to her admission, she presented with cessation of menses. Two months prior to admission, she had bilateral temporal loss of vision. The patient had no known prior infection or surgical procedure done. The patient was fertile and was able to conceive twice before. Apart from bitemporal hemianopsia, the rest of the physical examination was normal. Preoperative diagnosis was a non-functioning pituitary adenoma with hypopituitarism and optic chiasmal compression. During transsphenoidal surgery, instead of a solid mass, there was egress of purulent fluid upon puncturing of the capsule, findings compatible with an abscess. There was immediate improvement in visual acuity and visual fields after surgery. The patient was treated with intravenous ceftriaxone 2 g every 12 hours for 14 days. She developed a cerebrospinal fluid leak, which was successfully treated with acetazolamide and drainage of CSF via lumbar tap. There was no post-operative diabetes insipidus.
Magnetic resonance imaging (MRI) of the pituitary gland showed a hetergenous sellar-supra-sellar rim-enhancing mass (Figure 1).
Prior to surgery, her pituitary function was evaluated. Hyperprolactenemia as the cause of amenorrhea was ruled out because the prolactin level was normal at 92.2 uIU/ml, (N: 92-868). The patient had hypogonadotrophic hypogonadism as shown by the low follicle stimulating hormone (FSH) 0.35 miU/ml (N: 0.6-9.5) and low estradiol 29.7 pg/ml, (N 127-476). The patient also had secondary hypothyroidism her TSH 0.5 muiU/ml (N: 0.3-5.4) and fT4 9.4 pmol/L (N: 11-24) were both low. The patient also had secondary hypocortisolism with an 8AM cortisol of 39.54 nmol/L (N: 138-690). Serum adrenocorticotrophic hormone level was not determined.
The patient did not present with diabetes insipidus. The pre-operative serum sodium was 136 mmol/L, postoperative serum sodium was 135 mmol/L (N: 136- 144). Preoperative urine specific gravity was 1.024 and post operative urine specific gravity was 1.012.
There was no history of antecedent infection. There were no signs and symptoms such as fever. The patient had clear breath sounds and normal examination of the abdomen and genital area. Complete blood count showed a hemoglobin of 127 g/L, (N: 135-180), white blood cells 5.23 x109/L (N: 4.5-11.0), neutrophils 41% (N: 50-70%) and lymphocytes 46% (N: 20-50%).
Histopathology showed benign cyst contents (Figure 2). Gram stain of the abscess showed a PMN 0-1/OIF, Grampositive cocci 0-1/OIF. However, the abscess culture had no growth after 5 days of incubations. Work up for tuberculosis was also negative. Acid-fast bacilli smear was negative, as well as the polymerase chain reaction for M. tuberculosis.
The primary treatment for pituitary abscess is drainage. Empiric antibiotic coverage with Ceftriaxone 2 grams was given intravenously every 12 hours for 14 days. Patient had immediate improvement of blurring of vision post-operatively. The patient was able to count fingers during visual field confrontation test. There was no post-operative diabetes insipidus. Patient had cerebrospinal leak, which was resolved by giving acetazolamide. Patient was discharged on prednisone 7.5 mg/day and levothyroxine 100 mcg/tab, once a day. | null | Not supported with pagination yet | null |
PMC8092082_01 | Female | 0 | A mother accompanied with her 1-month and 2-week-old girl reported to the casualty wing of a local referral hospital complaining that her child was experiencing bleeding from the gums after removal of four "plastic teeth" by a local healer a day before. According to her history, the child had been well until a day before (December 8, 2019) when she started crying incessantly for unknown reasons. The following day, she decided to take the child to the nearest clinic for evaluation. However, on her way to the clinic, the mother met a local traditional tooth extractor, and this woman advised her that the cries of the child were due to the presence of "plastic teeth" that needed to be removed for the child to stop crying. The belief by the community is that the prominence seen on gum pads in the areas where canine tooth buds are developing [Figure 1 with arrows pointing to the primary canine bulge], contains "worms" which are the cause of high fever, diarrhea, and vomiting in a child.
After the enucleation of the primary canines, the child started experiencing severe bleeding from the gums, episodes of vomiting blood clots, and voiding black tarry stool that lasted for nearly 15 h, before the decision to seek for medical help from the hospital on December 10, 2019.
At the emergency room of the hospital, enquiry into the baby's past medical history was unremarkable. A review of the antenatal history indicated that the child had been born at 34-week gestation through a cesarean section and had a good "appearance, pulse, grimace, activity, and respiration or APGAR" score. Postnatal history revealed that the child had had no history of treatment for fever or any other infections but had been exclusively breastfed and fully vaccinated and her developmental milestones were normal. On family and social history, the baby was a firstborn, and there was no known history of bleeding disorders in the family.
Initial assessment showed an extremely pale child, who had copious amounts of fresh blood mixed with clots within the oral cavity, and which was cleaned and sucked out from time to time [Figure 2].
There were associated episodes of vomiting clotted blood and voiding of black tarry stool, but no change in urine color. Examination of the abdomen revealed nontender but distended abdomen. Other systems were essentially normal. Local examination of the oral cavity after evacuation of the blood clots showed wounds in all the four quadrants in the canine regions. The nostrils had visible clotted blood. An initial impression was made of severe anemia and septicemia secondary to traumatic teeth extraction. The child was immediately admitted and put on oxygen via nasal prong and antibiotics, and after blood match was done, blood transfusion was commenced, as further investigations continued. A final diagnosis of disseminated intravascular coagulopathy was reached, and the full range of treatment given to the child at the hospital is shown in Table 1. The treatment given to the child was aimed at correcting hemodynamic instability and control of sepsis. However, throughout the admission, the vital signs deteriorated until the child succumbed to the effects of IOM on December 10, 2019, at 12.45 pm, a few hours postadmission. During all this period, it was not possible to obtain an intraoral photograph of the child, and because of the child's loss of blood and eventual death, the final diagnosis of what initially caused the discomfort the child had was never actually elucidated. | enucleation of primary canines, infant oral mutilation, traditional dental practice | Not supported with pagination yet | null |
PMC10162194_01 | Male | 61 | We report the case of a 61-year-old male with a history of heartburn (treated with PPI omeprazole) and systemic sclerosis with intestinal involvement, with secondary chronic diarrhea. He reported instability for 10 days, which progressively worsened until he was unable to walk. During his physical examination, we observed dysarthria, truncal ataxia and limb ataxia predominantly affecting the left side (18 points on the SARA scale). Afterwards, he presented with a tonic-clonic seizure, requiring hospital admission.
Given the rapidly progressing ataxia and epilepsy, we performed a brain MRI, which showed T2 hyperintensity in the cerebellar hemispheres (Figure 1), suggestive of vasogenic edema. Hence, we considered cerebrovascular etiology unlikely, given the progressive course and the absence of compatible findings in MRI. In light of the patient's history of systemic sclerosis, we also considered autoimmune etiology, but discarded this option because of the absence of systemic symptoms and the normal results returned by a comprehensive autoimmunity assessment (including onconeural antibodies). A cereberospinal Fluid study showed no anomalies, all serologies were negative, and the patient never presented with fever; therefore, infectious etiology was ruled out.
Finally, we considered toxic-metabolic etiology. A blood analysis revealed severe hypomagnesemia (0.31 mg/dL, normal levels 1.8-2.6 mg/dL), which was probably secondary to treatment with PPI and the chronic diarrhea. Therefore, we commenced supplementation, which corrected the patient's Mg levels over the course of the following days, leading to progressive clinical improvement of the cerebellar syndrome, with only mild dysarthria persisting at hospital discharge (1 point on the SARA scale).
Therefore, the final diagnosis was cerebellar syndrome and epileptic seizures secondary to hypomagnesemia.
Cerebellar dysfunction secondary to hypomagnesemia has rarely been reported in the past; and various authors have postulated that the dysfunction may be a distinct disease. This dysfunction typically presents with dysarthria and ataxia, with clinical improvement after correction of hypomagnesemia. In neuroimaging, hyperintensities compatible with cerebellar edema have been described in T2-weighted images. Various treatments have been tested, including corticotherapy and thiamine administration; however, early Mg replacement is the only measure that has shown clinical and radiological improvements.
The pathophysiology is unknown. It has been proposed that endothelial dysfunction could be the main factor contributing to cerebellar affection, with a mechanism similar to that proposed for Posterior Reversible Encephalopathy Syndrome (PRES).
In the reported case, cerebellar ataxia was the initial manifestation of severe hypomagnesemia, preceding other major clinical complications by days. The neuroimaging findings, consistent with the clinical condition described, reaffirmed the suspicion. Early supplementation with Mg probably contributed to the good clinical response observed. | ataxia, hypomagnesemia, neuroimaging | Not supported with pagination yet | null |
PMC7688996_01 | Male | 62 | A 62-year-old man with a past history of chronic obstructive pulmonary disease and recent ischemic cerebral stroke was referred to the department of Urology for an acute urosepsis. The patient was suffering from recurrent cystitis and a spontaneous rupture of the right upper urinary tract treated by antibiotics only (Ciprofloxacin).
On admission, the patient presented fever, pelvic pain, dysuria and urinary retention which was treated by a transurethral catheter.
On examination, the patient was febrile (39 c) with tachycardia and low blood pressure (90/50 mmHg). Digital rectal exam was painful and abdominal examination was normal.
Blood analysis showed a neutrophilic leukocytosis and a high C-reactive protein level (256 mg/L).
Urinalysis revealed alkaline urine (ph = 7,6) with pyuria and hematuria.
The diagnosis of an urosepsis caused by urinary infection was highly suspected.
The patient was hospitalized, probabilistic antibiotherapy based on ofloxocin and ceftriaxone was prescribed until urinary culture results are ready.
A CT scan was performed and showed a calcified thickening of the whole bladder (Fig. 1), a moderate hydro-nephrosis in the right side with a small calcification on the right renal pelvis. (Fig. 2).
After 24 h, the patient was afebrile, without tachycardia and blood pressure was normal.
Regarding this radiological aspect of the bladder, a cystoscopy was performed seven days later and showed a calcified, hyperemic and fragile bladder with a thickened wall involving the whole bladder (Fig. 3).
Multiple biopsies during endoscopy were performed.
Many diagnoses were suspected such as muscle invasive tumor, urinary tract bilharziasis, tuberculosis and encrusted cystis.
Biopsies were sent for pathological and parasitological analysis.
In addition, a non-specific and specific bacteriological culture for Corynebacterium and tuberculosis were carried out.
Bacterial culture results were positive to CBGD2.
The diagnosis of encrusted cystitis and pyelitis was highly considered.
An adapted antibiotherapy was undertaken using vancomycin 15 mg/kg every 8 h during 3 weeks.
Four days later, the patient presented an acute peritonitis with acute abdominal pain and abdominal tenderness.
A laparotomy was performed urgently. An unusual Bladder rupture in the dome, far from biopsy location, was found. Surgical repair was realized.
On pathological examination, the photomicrograph showed an extensive bladder mucosal ulceration with necrosis and microcalcifications and increased vascularity of the lamina propria (Hematoxylin and Eosin (HE) x40) (Fig. 4A). A high power view showing microcalcifications and necrotic debris surrounded by an inflammatory cellular infiltrates of lymphocytes, eosinophils, histiocytes and foreign body giant cells (HE x400) (Fig. 4B).
The diagnosis of encrusted cystitis was confirmed by histological findings.
A cystectomy was discussed but we opted for a conservative treatment based on literature finding.
The diagnosis of encrusted cystis was confirmed by anatomo-pathological exam.
Seven days later, a second laparotomy was performed because of an acute peritonitis due to complete bladder rupture. The Bladder reparation was not possible and a complete cysto-prostatectomy and bilateral ureterostomy were performed.
The post operative outcomes were uneventful. Vancomycin was carried on during 3 weeks. Bacterial urinalysis was negative.
Control CT-scan showed pyelic calcification regression and the patient was discharged home. | corynebacterium urealyticum, cystectomy, encrusted cystitis, encrusted pyelitis | Not supported with pagination yet | null |
PMC3489167_01 | Female | 16 | Kaitlin1 was a Russian-born 16 year old female living at home with her younger brother (age 13) and biological parents. At intake, Kaitlin's percentile for body mass index (BMI; kg/m2) based on age and gender was 19, indicating that her weight was not consistent with AN. Records obtained from her pediatrician indicated that her BMI was consistently between the 10th and 20th percentile throughout her development. By clinical interview, Kaitlin reported loss of control over eating approximately 24 times per week and 35 episodes of purging per week. Kaitlin experienced a sense of loss of control while eating a single item of food when the food was unplanned or contained a large proportion of carbohydrates. Her purging episodes would follow these subjective binge episodes (SBEs), but also occurred when her mood was particularly low, or she generally felt 'out of control' of some other aspect of her life. She denied any laxative or diet pill use. Her exercise was infrequent, but when it occurred, it was compulsive in nature. In addition, Kaitlin reported notable body image disturbances, believing that she was fat and that her appearance was "appalling" to others. As is common among patients with eating disorders, she alternated between weighing herself multiple times per day and avoiding the scale altogether.
Katlin also reported significant mood swings, varying from happy and easy going to angry and depressed, but although she endorsed these symptoms, Kaitlin did not meet full criteria for any specific DSM-IV mood disorder. Her parents also described regular angry outbursts. Kaitlin's sleeping pattern was irregular, as she would often wake in the middle of the night to binge and/or purge, which resulted in only an average of 3-4 hours of continuous sleep per night and approximately 7 hours total. Katlin was diagnosed with attention deficit/hyperactivity disorder (ADHD) in 1st grade and since that time, she had been treated primarily with medication (e.g. methylphenidate). When she presented for treatment, she was prescribed 40 mg/day of Straterra (atomoxetine).
At the onset of her eating disorder, Kaitlin's parents were not overly concerned by her symptoms, and some behaviors were even viewed positively by her family as attempts to "get healthy." For example, Kaitlin's parents addressed her irregular but compulsive exercise by offering to provide her with a personal trainer for more consistency in her physical activity, and responded to her out of control eating by suggesting a consultation with a nutritionist to help Kaitlin eat more healthy foods. However, as her eating disorder continued, her symptoms exacerbated problems within the family.
Kaitlin's father was the primary advocate for adopting more "healthy" behaviors, and a number of his suggestions supported the maintenance of Kaitlin's eating disorder, which was a source of frustration for Kaitlin. Kaitlin's father would point out inconsistencies in her eating and exercise as a means of motivating his daughter to change, but she would experience these comments as painful and shaming, become upset, and verbal conflicts would often ensue. Her mother typically mediated these arguments, and believed that if Kaitlin were just able to lose "a few pounds," she would be happy and her problematic behaviors and the fighting with her father would subsequently decrease. Different responses to Kaitlin's eating disorder also reflected divergent parenting styles, with her father acting as a motivating and energizing force with a focus on achievement in the family, and her mother providing a calming presence, support, and nurturance. At the start of treatment, the family was particularly destabilized due to the frequency of fighting between Kaitlin and her father, and her mother and brother were unable to successfully work to mediate the conflicts.
The ability to simultaneously address Kaitlin's symptoms and other maintaining mechanisms using an evidence based treatment (CBT-Eb) provided a distinct advantage in treatment planning and execution. Kaitlin's weight was not consistent with a diagnosis of DSM-IV AN, and she described binge eating episodes where she did not consume "an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances", which meant that she also did not meet criteria for a diagnosis of DSM-IV BN. Thus, she was assigned a diagnosis of an EDNOS; however, her symptoms were consistent with a syndrome labeled "purging disorder". Although the definition of this syndrome varies, it is typically characterized by recurrent episodes of purging either with or without SBEs. The clinician (TBH) decided to use CBT-Eb with Kaitlin as this type of treatment is efficacious for patients with BN and normal-weight EDNOS, and purging disorder shares an important behavioral target with BN (purging).
Kaitlin attended 29 sessions of treatment over 9 months. When Kaitlin and her family first presented, they began a course of Maudsley family therapy (MFT), an empirically-supported treatment for adolescents with BN. Consistent with this approach as described for adolescents with BN, the first session following an intake assessment primarily involves raising the anxiety of the parents and placing them in charge of regulating their child's eating. However, it was very difficult to complete the session. Kaitlin and her parents frequently argued, about the eating symptoms and other unrelated issues, which was indicative of a significant degree of expressed emotion, typically in the form of parental criticism. By the end of the first session of MFT, both Kaitlin and her father were very angry and refused to participate in the treatment as designed.
As outlined in the MFT manual, a decision was made to proceed in split format whereby the therapist would meet with Kaitlin and her family separately, each of whom would be allotted half of the session. Over the course of 3 split sessions of MFT, Kaitlin's rate of vomiting accelerated, from 3-5 times per day to 6-8 times per day (see Figure 1). Kaitlin believed the increase in vomiting was related to conflicts with her parents that occurred multiple times per day. Based on existing evidence from empirical studies of MFT, the degree of expressed emotion among the family was deemed detrimental to continuing with this form of therapy. The therapist recommended a course of individual CBT-E, and despite the problems during MFT, Kaitlin was motivated to eliminate her eating disorder symptoms and agreed to try this type of treatment.
The transition to CBT-E began with a formal agreement on a case formulation between Katlin and her therapist, which was developed from observations over the initial MFT treatment sessions and assessment. At this point, Kaitlin indicated that she believed the therapist understood her eating disorder and many of the proximal triggers for her eating disordered behavior. In both CBT for BN and CBT-E, self-monitoring is initiated in the first session. Kaitlin's problems related to remembering tasks and general inattention exacerbated her difficulties with keeping food records. To help keep this therapy assignment present in her mind, Kaitlin and her therapist created several environmental "triggers" for self-monitoring. First, Kaitlin created a phrase that reminded her of the assignment and entered it as her cell phone "name" such that every time she checked her cell phone she would be reminded to self-monitor. Second, between-session phone check-ins were instituted as a means to problem-solve around self-monitoring. Phone contact occurred daily for the first week, but transitioned from therapist-initiated phone calls, to messages left by Kaitlin on the therapist's voicemail noting her progress with self-monitoring. Between-session contacts were intended to reinforce any self-monitoring attempts, normalize difficulties with monitoring, and continue to support the assignment of monitoring after every eating and purging episode. Thirdly, Kaitlin's mother was recruited to help with her assignments. Kaitlin and her mother had previously agreed on a system of rewards for schoolwork whereby Kaitlin received a small reward if she finished all of her work for the week. Rewards usually consisted of money for a manicure, to download music, or to go to the movies. Kaitlin and her mother decided to include assignments from therapy into this established reward system. The goal was to provide parental involvement in the CBT-E while maintaining a developmentally appropriate degree of autonomy for Kaitlin, similar to that described by.
After the initiation of self-monitoring, Kaitlin was assigned the task of regular eating, or consuming three planned meals and two snacks per day, with no more than four hours between meals/snacks. Regular eating was particularly difficult for Kaitlin at school because her friends generally skipped lunch, and she was very sensitive to appearing different from her friends. On the weekends, Kaitlin ate a mid-day meal without a problem. To address this obstacle, Kaitlin agreed to conduct a behavioral experiment of eating lunch with one of her friends on the weekend and evaluating her friend's response. She agreed to use this experience to subsequently make another hypothesis about how her friends would respond to her decision to eat lunch at school. This pattern set the stage for a number of behavioral experiments targeting obstacles to regular eating and eventually the incorporation of forbidden foods.
To address her vomiting episodes, the therapist reviewed Kaitlin's self-monitoring records to identify triggers, most of which involved eating foods that she tried to exclude from her diet (forbidden foods), or a sensation of fullness/fatness after eating. Other triggers included mood swings, early waking, and interpersonal conflict with her parents or friends. Self-monitoring alone reduced her purging episodes; however, the primary intervention was to delay the use of purging as a coping mechanism. Kaitlin's mother was again recruited to provide rewards for any delays in her purging. Delays became progressively longer from session to session, with the goal of reaching 1 hour between the trigger and purging. Simultaneously, Kaitlin began utilizing alternatives to purging, which were introduced as a form of 'self-care'. In some cases these activities were preventative (i.e., planning to do a yoga tape if she awoke early in the morning) or instituted at the onset of the trigger (i.e., listening to a song from her favorite band).
Initially, Kaitlin was weighed in session after her parents removed the scale from her bathroom, but she could not tolerate seeing her weight at this time, particularly after having experienced an increase in SBEs during the initial course of family therapy. Psychoeducation about weight was provided, but this information did little to reduce Kaitlin's anxiety about the possibility of weight gain. Kaitlin was asked to step on the scale in session without looking at the weight and remain on the scale until her anxiety decreased. This process was repeated at each session, and the amount of exposure was gradually increased until the end of phase I, when Kaitlin could weigh herself in session and tolerate seeing her weight.
The significant decrease in both Kaitlin's binge eating and purging episodes during the first phase of CBT-E is illustrated in Figure 1. As outlined in the CBT-E manual, after the first phase of treatment, the focus of the sessions shifted to reformulating Kaitlin's eating disorder based on the progress she had made to that point. A separate visit was also held with her parents to discuss the changes in Kaitlin's symptoms during the prior six weeks and to incorporate their impressions of the maintaining mechanisms for her remaining symptoms into the treatment plan. In the reformulation process, two major obstacles that prevented Kaitlin from achieving abstinence from her eating disorder were identified by Kaitlin's parents and her own observations. She continued to fight frequently with her family and feared being disliked by her friends. Furthermore, her mood swings complicated her interpersonal relationships with both family and friends and reflected a general difficulty tolerating affective states. Based on this re-formulation, the choice was made to implement CBT-Eb including a focus on mood-related changes in eating and interpersonal functioning. The mood intolerance component of CBT-Eb and the symptoms. interpersonal module were selected because these areas significantly impacted Kaitlin's ability to achieve abstinence from her eating disorder symptoms.
In practice, once additional maintaining mechanisms and modules are chosen in CBT-Eb, half of the session is allotted for addressing ongoing bulimic behaviors, and half for a modular treatment. This format was also used when addressing mood intolerance, and Kaitlin continued to build upon the progress she made in the initial phases of treatment. A series of assignments were developed for dealing with mood intolerance, including: alternative behaviors (e.g., brushing her dog when she felt sad), slowing down and observing emotions (e.g., distancing herself from her negative mood and observing how long it lasted), and making the choice to behave in a manner that was the opposite of what she felt at the moment (e.g., reaching out to a friend when she felt like withdrawing from social contact). Reinforcement from the therapist via phone check-ins was available to Kaitlin during this time as a form of shaping behavior, but only prior to a binge eating or purging episode. When the patient called after an episode, the call was not returned until the next day and then was only limited to a risk assessment. Kaitlin's mother continued to provide small reinforcements for completing therapy assignments, but solely for finishing assignments and rewards were not contingent on whether the assignments had an appreciable impact on symptoms.
The remaining sessions addressed binge eating and purging and interpersonal problems. Reductions in parental conflict, particularly with her father, had already occurred as a result of Kaitlin's work on mood tolerance. As Kaitlin learned different ways to deal with her moods, her father began to adopt some similar strategies, which allowed the sessions to focus on residual interpersonal deficits. Two specific behaviors often led to interpersonal conflict. The first was Katilin's tendency to be very critical, particularly about the shape and/or weight of her friends. While she felt that her friends exhibited similar standards and said she "preferred the honesty" of her friends about this topic, the practice usually only resulted in hurt feelings, gossiping, and interpersonal threats (e.g., ignoring friends, recruiting friends to shame other friends, and public humiliation). Together, Kaitlin and her therapist discussed strategies for eliminating these behaviors and replacing them with more pro-social behaviors. In some instances, role plays were used to rehearse specific responses to criticism and others' interpersonal threats. These interventions had the unintended effect of improving Katlin's relationship with her father. While his interactions with her could still be distressing, her responses limited the degree of conflict and ultimately improved the relationship. Over the course of this module, Kaitlin identified two friendships that she felt were particularly problematic and most of the work targeted these relationships. As individual treatment with Kaitlin had been successful in helping to increase stability within the family to this point, the work on interpersonal relationships was primarily patient-oriented, and switching to a more traditional family therapy was not considered.
By the end of this phase of treatment, Kaitlin's purging had ceased and she no longer reported experiencing a sense of loss of control around food. However, Kaitlin had body image concerns that persisted, and while she was able to tolerate this disturbance, she would still criticize her appearance and generally believed herself to be fat. She rationalized these cognitions using the idea that most people had similar thoughts, and she was not going to let the thoughts interfere with her life. The interventions for body image described in CBT-Eb involve reducing checking and avoidance behaviors and diversifying self-evaluation beyond shape and weight. These interventions were not used explicitly during this course of treatment, although Kaitlin had made some improvements in this area through changes in her other symptoms. As she spent less time engaged in her eating disorder, many of these changes occurred naturally.
The final phase of treatment included a transition from weekly to bimonthly sessions, and Kaitlin practiced becoming her own therapist. As a reward for her work on her eating disorder during the prior 21 weeks, Kaitlin was given permission to attend summer camp, an opportunity she was excited about since a childhood friend was also planning to attend to the same camp. During this phase, Kaitlin began initiating her own goals for treatment and reporting them to her therapist. She created a system to provide her own reminders about the skills she needed to employ, using her cell phone to help her remain mindful of certain interventions. For example, she created a system called 'random acts of kindness' where she would engage in some form of a 'good deed' independent of her mood. This good deed could be as simple as telling her mother that she loved her, or sending a friend a complementary text message.
The final few sessions focused on relapse prevention while reviewing progress made during treatment, and specific plans were designed to handle lapses in symptoms and thresholds for seeking help. A written relapse prevention plan was developed in collaboration with Kaitlin, and once a final version agreed upon by therapist and patient, a copy was given to both the patient and her parents. If any episodes of binge eating or purging occurred, the plan involved re-initiating self-monitoring, seeking helpful alternatives, and asking others (e.g., her mother) for help. Kaitlin only had one lapse during this phase, triggered by a friend calling her fat. Although some residual concerns about shape and weight in combination with similar interpersonal situations might have increased Kaitlin's likelihood for relapse, she was able to utilize this plan without assistance from her therapist and described the experience as a success at her final session, and the treatment was concluded.
This case study illustrates that it is possible to successfully use CBT-Eb with developmentally appropriate adaptations in the treatment of a young patient with an EDNOS diagnosis, as suggested by. Kaitlin's treatment was similar to the adapted approach described by by involving the patient's mother from the beginning of treatment through brief conjoint meetings, the creation of a treatment formulation, regular consultation with the patient's medical providers, the use of real-time self-monitoring, in-session weighting, age appropriate psychoeducation regarding eating and weight problems, and regular eating. The treatment was longer than described by for adolescents who are not significantly underweight, but the additional sessions were considered necessary for material focused on mood intolerance and interpersonal functioning to be implemented in a manner appropriate for Kaitlin's developmental stage. In addition, the therapist focused less on engaging the patient in treatment and motivation to change than might be expected with other adolescents receiving CBT-E. Kaitlin entered treatment highly motivated to eliminate her symptoms, and continued to respond to the behavioral reinforcements throughout the course of therapy. Finally, the therapist employed between-session phone check-ins for reinforcement and shaping, and to accommodate some of Kaitlin's ADHD symptoms, and used a form of exposure to decrease her anxiety related to in-session weighing.
At this time, the lack of data for adolescents beyond a single case is a significant challenge to evaluating the utility of enhanced cognitive behavioral approaches for younger patients, or purging disorder in particular. Similarly, limited information is available to inform the treatment of adults with an EDNOS. However, the positive results of this case study are consistent with those reported by in a sample of normal-weight adults with an EDNOS, and a study by using a guided self-help form of CBT for adolescents with BN or EDNOS, which included normal-weight individuals who reported inappropriate compensatory behaviors without binge eating. For future research, possible strengths of CBT-E for youth include: the ability to treat patients with EDNOS, including adolescents, given their overwhelming presence in clinical populations, and the possibility of increasing the ease of disseminating an empirically-supported treatments for eating disorders, because training in only one manual would be required.
This case introduces some interesting clinical questions related to the family system, in particular, the primary involvement of Kaitlin's mother in the monitoring and reinforcement process, and the effect of the choice to discontinue, and not resume, family therapy. There were potential disadvantages to only involving Kaitlin's mother in CBT-Eb. It was possible that because of her more primary role in the treatment, Kaitlin's mother would feel overburdened by an increase in her responsibilities within the family, and there was a risk for more miscommunication between Kaitlin and her father due to his limited involvement in the treatment. Kaitlin's father could have continued to reinforce her eating disorder symptoms because he did not participate in developing therapy assignments, or might have even undermined contingencies agreed upon by Kaitlin and her mother. Among the advantages to primarily involving Kaitlin's mother were reducing stress within the family due to fewer conflicts between Kaitlin and her father, and allowing Kaitlin greater autonomy to manage and change her eating disorder symptoms.
Either MFT or a traditional form of family therapy could have been delivered conjointly or resumed following Kaitlin's individual treatment. It is not possible to know whether augmenting or sequencing family therapy would have amplified the gains Kaitlin experienced from CBT-Eb. However, traditional family therapy could have addressed issues such as the disparate parenting styles between Kaitlin's mother and father, or helped in identifying her symptoms as a means for communicating basic needs to her parents. The initial sessions of MFT also helped to externalize Kaitlin's symptoms, and reduced the tendency for the family to blame her for the eating disorder, gains that might have continued with additional MFT. One potential concern with utilizing conjoint MFT is the focus on empowering both parents to assist with symptom control, which could have increased the pressure on Kaitlin's mother to manage both the parenting style of Kaitlin's father's and Kaitlin's reactions to family conflicts. It is possible that once Kaitlin had experienced some relief from her eating disorder, she may have been better equipped to handle this approach, but the use of individual therapy alone produced a clinically meaningful change in her symptoms.
The results of this case highlight a few important concepts. First, assessing the degree of expressed emotion in the home environment is particularly important when a clinician is making initial decisions for how to proceed with an adolescent. Attention should be paid to the way in which individuals in the family respond to one other when they are upset or frustrated. When a high degree of expressed emotion is present, CBT-E may offer advantages over MFT. Secondly, the presence of mood intolerance and interpersonal problems can affect an adolescent's functioning independent of his or her eating disorder. For Kaitlin, mood and interpersonal issues exacerbated her eating disorder, but also caused distress independent of her eating pathology, which contributed to the difficulty in assigning specific comorbid diagnoses. CBT-Eb offers a means for targeting these other issues along with the eating disorder, which can improve the patient's bulimic symptoms, overall affect, and family or peer relationships. Finally, the application of a successful individual treatment helped create an environment that reinforced positive change within the family and greatly improved the overall quality of their relationships. | null | Not supported with pagination yet | null |
PMC4904554_01 | Male | 12 | A 12-year-old boy presented to the Paediatric Emergency Department with a three-month history of daily fever, migratory arthritis, angular cheilitis, a reported 5 kg weight loss, and malaise. Past medical history was unremarkable other than immigration from Pakistan to Canada at the age of 7. Family history was significant for parental consanguinity (first cousins), but both parents and an older brother (17 years) and sister (19 years) were reported as being well.
He was admitted to hospital for a diagnostic evaluation and was found to have systemic inflammation (elevated c-reactive protein, erythrocyte sedimentation rate, ferritin, sCD-163, and sCD-25) concerning macrophage activation syndrome (MAS). He underwent an extensive workup for potential secondary causes of this inflammation. Bacterial blood culture, EBV/CMV, Toxoplasma gondii, parvovirus B19 and Legionella serologies, respiratory virus multiplex PCR, and TB skin test were negative. An abdominal ultrasound and bone marrow aspirate showed no evidence of malignancy. An autoantibody panel was sent and was positive only for anti-nuclear antibody (1 : 160, speckled pattern). A chest X-ray was performed and was normal.
At this time, a clinical diagnosis of systemic onset juvenile idiopathic arthritis was made. Treatment with oral prednisone (60 mg orally, once daily) was initiated on day 3 of admission, which resulted in rapid resolution of the fevers, arthritis, and cheilitis. He was discharged home on day 6 of admission with follow-up planned with Rheumatology.
He presented to the Emergency Department 3 weeks later with a three-day history of fever, cough, and pleuritic chest pain. Chest X-ray revealed bilateral, multifocal pulmonary nodules and chest CT confirmed the presence of bilateral, predominantly apical homogeneous nodules (5-20 mm in diameter) and hilar lymphadenopathy (Figure 1(a)).
The main differential diagnosis of this child's pulmonary nodules was infectious. A bronchoalveolar lavage revealed the presence of Aspergillus fumigatus and treatment with voriconazole was subsequently initiated. | null | Not supported with pagination yet | null |
PMC8348509_01 | Male | 37 | A 37-year-old Japanese man with a 4-month history of fever, cough, and dyspnea with abnormal chest X-ray findings was referred to a respirologist. He had no past history, including allergic diseases, asbestos exposure or recent trauma, and was on no regular medications, including dietary supplements. He had never eaten raw meat or freshwater fish. On physical examination, his temperature was 37.8 C, and respiratory sounds were decreased on the left side, with no abnormal respiratory sounds. He had no skin rash, bruises, or sensorimotor disorders. Chest radiography showed decreased permeability in the left lower lung field (Fig. 1a), and dynamic chest computed tomography showed a pleural effusion with passive atelectasis and pleural thickening on the left side (Fig. 1b and c). Thrombosis in the pulmonary artery and other abnormalities were not observed. On laboratory examination of the pleural effusion, the white blood cell count was 3200/muL, with 68.0% eosinophils, and total protein was 4.8 g/dL, albumin was 2.8 g/dL, and lactate dehydrogenase was 796 IU/L, indicating an exudative pleural effusion with no malignant cells on cytology and no detection of pathogens, including tuberculosis. Adenosine deaminase was 26.8 IU/L. These results were the same on examination of his other pleural effusion specimen. Blood tests showed a white blood cell count of 14,900/muL, and eosinophils were 68.0%, with no abnormal lymphocytes or hemocytoblasts. Total IgE was 730 IU/mL, and C-reactive protein was 1.57 mg/dL. Other results including liver enzymes, rheumatoid factor, antinuclear antibody, anti-neutrophil cytoplasmic antibody, and urinalysis were normal. Parasite IgG in serum, and examinations for helminth eggs were negative in stool and the pleural effusion. A thoracoscopic pleural biopsy was performed, and eosinophilic infiltration with inflammatory granulation tissue was seen without fibrinoid necrosis or malignant cells (Fig. 2a). To rule out a myeloproliferative disorder, a bone marrow biopsy was performed, and normocellular marrow with 10% eosinophils in nucleated cells, with no maturity disorder of granulocytes and no increase of hemocytoblasts, was seen (Fig. 2b). Philadelphia chromosome, FIP1-like-1 (FIP1L1) - platelet derived growth factor receptor alpha (PDGFRA) fusion gene, platelet derived growth factor receptor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) were not detected. A diagnosis of idiopathic eosinophilic pleurisy was made, and the patient was treated with prednisolone 0.5 mg/kg/day with gradual tapering. After treatment, the fever, cough, and dyspnea resolved along with a decrease of blood eosinophils. His pleural effusion disappeared 3 months after treatment (Fig. 3a). Currently, he has had no recurrence for 10 months on treatment with 5 mg/day of prednisolone. | diagnosis, eosinophilic pleural effusion, eosinophilic pleurisy | Findings on chest X-ray and dynamic computed tomography (CT) before corticosteroid treatment. (a) Chest radiography shows reduced permeability in the left lower lung field. |
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PMC8348509_01 | Male | 37 | A 37-year-old Japanese man with a 4-month history of fever, cough, and dyspnea with abnormal chest X-ray findings was referred to a respirologist. He had no past history, including allergic diseases, asbestos exposure or recent trauma, and was on no regular medications, including dietary supplements. He had never eaten raw meat or freshwater fish. On physical examination, his temperature was 37.8 C, and respiratory sounds were decreased on the left side, with no abnormal respiratory sounds. He had no skin rash, bruises, or sensorimotor disorders. Chest radiography showed decreased permeability in the left lower lung field (Fig. 1a), and dynamic chest computed tomography showed a pleural effusion with passive atelectasis and pleural thickening on the left side (Fig. 1b and c). Thrombosis in the pulmonary artery and other abnormalities were not observed. On laboratory examination of the pleural effusion, the white blood cell count was 3200/muL, with 68.0% eosinophils, and total protein was 4.8 g/dL, albumin was 2.8 g/dL, and lactate dehydrogenase was 796 IU/L, indicating an exudative pleural effusion with no malignant cells on cytology and no detection of pathogens, including tuberculosis. Adenosine deaminase was 26.8 IU/L. These results were the same on examination of his other pleural effusion specimen. Blood tests showed a white blood cell count of 14,900/muL, and eosinophils were 68.0%, with no abnormal lymphocytes or hemocytoblasts. Total IgE was 730 IU/mL, and C-reactive protein was 1.57 mg/dL. Other results including liver enzymes, rheumatoid factor, antinuclear antibody, anti-neutrophil cytoplasmic antibody, and urinalysis were normal. Parasite IgG in serum, and examinations for helminth eggs were negative in stool and the pleural effusion. A thoracoscopic pleural biopsy was performed, and eosinophilic infiltration with inflammatory granulation tissue was seen without fibrinoid necrosis or malignant cells (Fig. 2a). To rule out a myeloproliferative disorder, a bone marrow biopsy was performed, and normocellular marrow with 10% eosinophils in nucleated cells, with no maturity disorder of granulocytes and no increase of hemocytoblasts, was seen (Fig. 2b). Philadelphia chromosome, FIP1-like-1 (FIP1L1) - platelet derived growth factor receptor alpha (PDGFRA) fusion gene, platelet derived growth factor receptor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) were not detected. A diagnosis of idiopathic eosinophilic pleurisy was made, and the patient was treated with prednisolone 0.5 mg/kg/day with gradual tapering. After treatment, the fever, cough, and dyspnea resolved along with a decrease of blood eosinophils. His pleural effusion disappeared 3 months after treatment (Fig. 3a). Currently, he has had no recurrence for 10 months on treatment with 5 mg/day of prednisolone. | diagnosis, eosinophilic pleural effusion, eosinophilic pleurisy | Findings on chest X-ray and dynamic computed tomography (CT) before corticosteroid treatment. (b, c) Dynamic chest CT shows a pleural effusion with passive atelectasis and pleural thickness on the left side. |
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PMC8348509_01 | Male | 37 | A 37-year-old Japanese man with a 4-month history of fever, cough, and dyspnea with abnormal chest X-ray findings was referred to a respirologist. He had no past history, including allergic diseases, asbestos exposure or recent trauma, and was on no regular medications, including dietary supplements. He had never eaten raw meat or freshwater fish. On physical examination, his temperature was 37.8 C, and respiratory sounds were decreased on the left side, with no abnormal respiratory sounds. He had no skin rash, bruises, or sensorimotor disorders. Chest radiography showed decreased permeability in the left lower lung field (Fig. 1a), and dynamic chest computed tomography showed a pleural effusion with passive atelectasis and pleural thickening on the left side (Fig. 1b and c). Thrombosis in the pulmonary artery and other abnormalities were not observed. On laboratory examination of the pleural effusion, the white blood cell count was 3200/muL, with 68.0% eosinophils, and total protein was 4.8 g/dL, albumin was 2.8 g/dL, and lactate dehydrogenase was 796 IU/L, indicating an exudative pleural effusion with no malignant cells on cytology and no detection of pathogens, including tuberculosis. Adenosine deaminase was 26.8 IU/L. These results were the same on examination of his other pleural effusion specimen. Blood tests showed a white blood cell count of 14,900/muL, and eosinophils were 68.0%, with no abnormal lymphocytes or hemocytoblasts. Total IgE was 730 IU/mL, and C-reactive protein was 1.57 mg/dL. Other results including liver enzymes, rheumatoid factor, antinuclear antibody, anti-neutrophil cytoplasmic antibody, and urinalysis were normal. Parasite IgG in serum, and examinations for helminth eggs were negative in stool and the pleural effusion. A thoracoscopic pleural biopsy was performed, and eosinophilic infiltration with inflammatory granulation tissue was seen without fibrinoid necrosis or malignant cells (Fig. 2a). To rule out a myeloproliferative disorder, a bone marrow biopsy was performed, and normocellular marrow with 10% eosinophils in nucleated cells, with no maturity disorder of granulocytes and no increase of hemocytoblasts, was seen (Fig. 2b). Philadelphia chromosome, FIP1-like-1 (FIP1L1) - platelet derived growth factor receptor alpha (PDGFRA) fusion gene, platelet derived growth factor receptor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) were not detected. A diagnosis of idiopathic eosinophilic pleurisy was made, and the patient was treated with prednisolone 0.5 mg/kg/day with gradual tapering. After treatment, the fever, cough, and dyspnea resolved along with a decrease of blood eosinophils. His pleural effusion disappeared 3 months after treatment (Fig. 3a). Currently, he has had no recurrence for 10 months on treatment with 5 mg/day of prednisolone. | diagnosis, eosinophilic pleural effusion, eosinophilic pleurisy | Findings on chest X-ray and dynamic computed tomography (CT) before corticosteroid treatment. (b, c) Dynamic chest CT shows a pleural effusion with passive atelectasis and pleural thickness on the left side. |
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PMC9647296_02 | Male | 34 | A 34-year-old man with no history of pulmonary disease was diagnosed with CML in September 2019 and was treated with 100 mg of dasatinib for 13 months. Although the dose of dasatinib was reduced to 80 mg because of cytopenia, he achieved an early molecular response at 3 months and maintained a major molecular response.
He visited the emergency department in October 2020 with complaints of CTCAE grade 1 fever and grade 2 headache persisting for 1 week. On examination, he was normotensive but showed fever and tachycardia of 38.3 C and 103 beats per minute, respectively. His respiratory rate was 19 breaths per minute, and oxygen saturation was 96% on room air. Physical examination results, including chest auscultation, were unremarkable. The WBC count was 4.05 x 103/microl, with 59.1% of segmented neutrophils. Except for elevations in grade 1 liver enzymes (aspartate transferase, 53 IU/L; alanine transferase, 51 IU/L) and mild elevation in CRP (1.52 mg/dl; reference range, 0-0.5 mg/dl), there were no significant abnormalities in other laboratory parameters. Chest radiography performed 1 week later showed no abnormalities. However, the fever persisted despite prescribing antipyretics; therefore, a chest CT scan was performed on the 11th day of fever. Chest CT findings revealed ill-defined GGO and consolidation, especially in the left lower lung field (shown in Figure 1(c)). Bronchoalveolar lavage (BAL) fluid analysis showed a lymphocyte-dominant pattern with no evidence of infection, including pneumocystis pneumonia (PCP), cytomegalovirus (CMV), respiratory virus, tuberculosis, or fungus. Echocardiography performed to exclude cardiac problems did not reveal any significant abnormal findings. Because of a suspected diagnosis of dasatinib-associated interstitial pneumonitis, dasatinib was discontinued. The fever resolved 3 days after the discontinuation of dasatinib, and TKI therapy was resumed 16 days after the discontinuation of the TKI, changing to imatinib. Follow-up chest CT performed after 3 months showed a decreased extent of the previously noted GGO (shown in Figure 1(d)). With regular outpatient department visits, the patient maintained molecular response 4.0, without significant toxicity to imatinib. | case report, chronic myeloid leukemia, dasatinib, drug-induced interstitial lung disease, tyrosine kinase inhibitor | Not supported with pagination yet | null |
PMC9647296_03 | Female | 46 | A 46-year-old woman was diagnosed with Philadelphia chromosome-positive ALL with a complex karyotype in February 2021. She received imatinib 400 mg/day with induction combination chemotherapy (daunorubicin, cyclophosphamide, vincristine, and dexamethasone) and achieved complete remission. During subsequent consolidation chemotherapy (methotrexate, cytarabine, and cyclophosphamide), the imatinib dose was reduced to 300 mg/day because of drug-related skin rash and generalized edema. Unfortunately, she developed a molecular relapse detected by BCR-ABL RT-qPCR after 6 months of imatinib treatment. The TKI was changed to dasatinib (140 mg/day).
One week after the start of dasatinib therapy, she developed CTCAE grade 2 fever (39.1 C) and dry cough. At the time of symptom onset, the respiratory rate was 24 breaths per minute and oxygen saturation in room air was 89.0%. The laboratory findings on admission were as follows: WBC count, 13.41 x 103/microl with 59.0% neutrophils; CRP, 2.84 mg/dl; procalcitonin, 0.13 ng/ml; aspartate transferase, 47 IU/L; and alanine transferase, 71 IU/L. Chest CT revealed diffuse GGO and peribronchial ill-defined nodules in the bilateral upper lobes, with a small amount of bilateral pleural effusion (shown in Figure 1(e)). BAL fluid analysis showed a lymphocyte-dominant pattern, and no microorganisms were identified, including PCP, CMV, respiratory virus, tuberculosis, or fungus. Empirical antibiotics were stopped, and considering that the patient was planning an allogeneic stem cell transplantation the next month, steroids were used without delay. Prednisolone at a dose of 1 mg/kg was started, and the dose was tapered off for 3 weeks. She showed symptomatic improvement, and follow-up chest CT showed resolution of diffuse GGOs in both lungs (shown in Figure 1(f)). The patient underwent haploidentical allogeneic hematopoietic stem cell transplantation from his son without significant toxicity. | case report, chronic myeloid leukemia, dasatinib, drug-induced interstitial lung disease, tyrosine kinase inhibitor | Not supported with pagination yet | null |
PMC6256173_01 | Female | 2 | Patient 1. A 2-years-old female infant was referred to the First Affiliated Hospital, Jinan University, due to elevated serum total bile acids (TBA) discovered for 21 months. At the age 3 months, she was admitted to Women and Children's Hospital of Quanzhou because of jaundice for 2 months. Laboratory test revealed that the serum levels of TBA, direct bilirubin (DBIL), aspartate transaminase (AST) and alanine transaminase (ALT) were all elevated (Table 1), and she was thus diagnosed to have cholestatic liver disease. After being treated with intravenous reduced glutathione and ademetionine-1,4-butanedisulfonate for 9 days, which were commonly used in cholestatic patients with elevated alanine transaminase levels, her jaundice was alleviated, but the liver function indices remained abnormal (Table 1). Then oral ursodesoxycholic acid was given and she was discharged at the age 3.3 months. During the subsequent follow-up over 20 months, she showed normal anthropometric and neurobehavioral development without abnormal appearance, and her cholestasis resolved completely since the age 7 months. However, persistently raised TBA levels were observed on repeated biochemical analyses (Table 1). So she was referred to our hospital for further investigation and management when aged 2 years.
The patient was the elder sister of two monochorionic diamniotic twins who was delivered by cesarean section at the gestation age of 37 weeks and 2 days with the birth weight 2.25 kg and body length 45.0 cm. Her father is a hepatitis B virus (HBV) carrier who was clinically healthy but with slightly elevated serum TBA level on biochemistry analysis, and her mother was physically and biochemically healthy (Table 1). There was no family history of any genetic disease.
Physical examination revealed a body weight of 12.0 kg, height 83.5 cm and head circumference 46.0 cm. No jaundice was observed in the skin and sclera. No stridor, crackles or crepitus was heard in the two lungs, and the heart sound was normal without any murmurs. There was no abdominal distention, and the liver and spleen were non-palpable. Physiological reflexes were normal and no pathological reflexes could be found on nervous system examination. On biochemical analysis, the TBA level reached 173.8 mumol/L (0-10 mumol/L) as other indices were normal (Table 1).
Patient 2 was the younger sister of patient 1, who also experienced transient cholestatic jaundice in early infancy and was referred to our hospital with the same complaint of persistently elevated serum TBA levels. As the younger one of two monozygotic twins, her birth weight was 2.30 kg and body length, 46.0 cm. On physical examination at referral, the body weight was 13.0 kg, height 85.0 cm, and head circumference 46.0 cm. No jaundiced skin or sclera was observed. Examinations of the lungs, the heart, the abdomen and nervous system were all normal. Her TBA level was 198.3 mumol/L (0-10 mumol/L), with otherwise normal biochemistry indices (Table 1).
Considering their refractory hypercholanemia whist lack of clinical symptoms and signs on physical examination, NTCP deficiency was highly suspected and hence Sanger sequencing of the SLC10A1 gene was carried out for all family members. As a result, the twins were both homozygotes of the variant c.800C>T (p.Ser267Phe), and their parents were both carriers of the same variant (Figure 1A). Electrophoresis of the PCR-RFLP products showed that the twins both harbored two additional bands of 164 bp and 65 bp rising from the aforementioned SLC10A1 variant, which further confirmed the SLC10A1 genotypes of all family members (Figure 1B).
NTCP deficiency was thus definitely diagnosed, and the twins were followed-up in the local hospital, and no specific medication was given. Thus far, the twins were both healthy but the serum TBA levels were still raised (Table 1), and their long-term outcomes needed to be observed. | slc10a1, bile acid, cholestasis, hypercholanemia, sodium taurocholate cotransporting polypeptide deficiency | Not supported with pagination yet | null |
PMC4926730_01 | Male | 42 | A 42 years old Asian male on evaluation of abdominal pain was diagnosed with adult polycystic kidney disease (ADPKD) in 2002. The patient's mother died of renal failure due to ADPKD. Patient had progressive deterioration of renal function and developed chronic kidney disease (CKD) stage 5 in 2015. The patient was advised renal replacement therapy (RRT) and required thrice-weekly hemodialysis since September 2015. He was evaluated for renal transplant and planned for the same in May 2016. During pre-transplant evaluation he developed fever with chills and bilateral painful cervical lymphadenopathy in the posterior triangle of neck. Ultrasound of cervical region reported presence of multiple enlarged lymph nodes in the neck along internal jugular vein on both the sides; largest node on right side measured 21x7 mm in size and on the left side largest node measured 16x5 mm in size. Ultrasound examination of axilla and groin did not reveal lymphadenopathy.
The patient underwent right cervical lymph node biopsy. Histopathology was reported to be acute necrotizing lymphadenitis. This biopsy was negative for acid-fast bacilli (AFB) and fungal stains. In the meanwhile his complete infectious screen of blood, urine, sputum and stool cultures showed no growth. The patient was given broad-spectrum third generation cephalosporins for 14 days assuming the fever to be caused by unidentifiable bacterial infection.
The fever settled and the patient was planned for a bilateral pre-transplant nephrectomy in view of bilateral large size kidney and recurrent fever. Right laparoscopic Pre-transplant nephrectomy was done on 05 February 2016. This was followed by a pre-transplant left open nephrectomy on 16 February 2016. The left side was planned for an open nephrectomy in view of the large size of the kidney. The procedure was uneventful. Incidentally, this was one of the largest kidney specimen ever recorded in literature weighing 2.35 Kg ( Figure 1a & 1b). The Guinness Book of World Records reports a kidney weighing 2.15 kg as world's largest kidney till now which was retrieved in Dhule, Maharashtra, India .
Postoperatively, the patient had continuous fever of 100 degree Fahrenheit with chills for 10-15 days; despite he receiving third generation broad-spectrum injectable antibiotics. As the patient had undergone a bilateral nephrectomy, the first diagnosis for pyrexia of unknown origin was postoperative surgical infection or intra-abdominal abscess formation. The imaging done included high-resolution computerized tomography (CT) chest (HRCT chest), CT abdomen and CT pelvis. These did not reveal any significant finding. His fever did not subside despite all the measures such as higher antibiotics, antipyretics and removal of all indwelling catheters. His indwelling catheter lines were cultured to rule out any infection, but did not grow any organism. An infectious disease specialist was consulted and he advised for a slide review of the cervical lymph node sample, which was done prior to nephrectomy.
Slide review with the specialist suggested a necrotizing histiocytic lymphadenitis (Kikuchi Disease) ( Figure 2a & 2b). Section revealed lymphoid architecture being replaced by necrotizing lesions, which are composed of karyorrhectic debris with fibrin deposits and collection of mononuclear cells. Plasma cells and neutrophils were scanty. Periodic acid-Schiff (PAS) stain was negative for fungal hyphae. Ziehl Neelsen (ZN) stain was negative for AFB with final diagnosis as necrotizing histiocytic lymphadenitis. Tests for bacteria/fungus/AFB were negative. Genexpert examination for tubercle bacilli (TB) was also negative. Immmunohistochemistry (IHC) examination for lymphoma was negative. Tests for systemic lupus erythematosus (SLE) were also negative. The key features which clinched the histological diagnosis were: karyorrhexis, fragmentation and necrosis.
The patient was started on non-steroidal anti-inflammatory drugs (NSAID), oral Prednisolone 10 mg twice a day for 15 days and continued on hemodialysis (HD). Patient responded well to this treatment measures. A team of an infection specialist, a nephrologist and a urologist managed this patient. The patient finally became afebrile and fit for renal transplantation after a treatment for 3 weeks. He underwent a living related renal transplant on 27 th of April 2016. His postoperative course after renal transplantation was uneventful and achieved a nadir creatinine of 1.05 mg/dl. | autosomal dominant polycystic kidney disease, kikuchi fujimoto disease, lymphadenopathy | Not supported with pagination yet | null |
PMC9887669_01 | Female | 51 | A 51-year-old woman was referred to a heart failure clinic for the evaluation of progressive cardiomegaly. She underwent dual-chamber pacemaker (Adapta ADD01 [the last generator change in 2015], Medtronic, MN, USA) implantation because of a high-degree atrioventricular block (AVB) 24 years ago and was followed up by an electrophysiology specialist. She was also treated for Type 2 diabetes mellitus for 23 years and underwent right total thyroidectomy for papillary thyroid cancer. She was taking subcutaneous insulin glargine 8 units once daily, metformin 1000 mg once daily, alogliptin 25 mg once daily, and glimepiride 4 mg once daily for Type 2 diabetes mellitus. Under these medications, her haemoglobin A1c level was 7.1%. She had been using hearing aids for 12 years after being diagnosed with sensorineural hearing loss and had been receiving antibiotic treatment, including azithromycin and ethambutol, for non-tuberculous mycobacterial lung disease for 2 years prior to this medical event. She had no family history of cardiac disease or genetic syndrome. A chest radiography revealed that her heart size increased progressively over the past 2 years (Figure 1).
When visiting a heart failure clinic, she complained of dyspnoea on exertion for 1 month. She also suffered from paraesthesia of her upper and lower extremities. Her blood pressure was 139/75 mmHg, and her pulse rate was 89 b.p.m. On physical examination, no abnormal finding other than a chronic ill-looking appearance was observed. A regular heartbeat without a murmur was observed, and her lung sounds were clear.
A transthoracic echocardiography revealed severe global hypokinesia of the left ventricle (LV) with an enlargement of the cardiac chambers (LV end-diastolic dimension was 56 mm); LV ejection fraction was estimated to be 26%. The myocardium showed a sparkling texture with fine bright particles, and the thickness of the interventricular septum and LV posterior wall increased to 11 mm from an echocardiography measurement of 7 mm in 2012. A small pericardial effusion was also noted. No valvular dysfunction was observed, except for Grade 1 mitral regurgitation. Mitral inflow showed a pseudonormalization pattern with elevated LV filling pressure (E/e' 20.2) (see Supplementary material online, Video). Interrogation from her pacemaker showed a 100% ventricular pacing record with an underlying complete AVB rhythm, which suggested complete dependency on the pacemaker. Her thyroid function was within the normal range in laboratory tests, but her serum sodium level was slightly low (126 mmol/L), whereas N-terminal pro-B-type natriuretic peptide (1961 pg/mL; reference range, 0-249 pg/mL) and troponin-T (39 pg/mL; reference range, 0-14 pg/mL) levels increased. Urinary tests showed heavy proteinuria (spot urine protein-to-creatinine ratio, 7.22 g/gCr; albumin-to-creatinine ratio, 5811 mg/gCr). Urine electrophoresis of 24-h-collected urine showed non-selective proteinuria. A nerve conduction velocity study confirmed the presence of bilateral sensorimotor polyneuropathy.
Several diagnostic examinations were performed for cardiac amyloidosis or other infiltrative diseases. Screening tests for Fabry disease revealed normal alpha-galactosidase activity. Serum and urine immunofixation revealed no abnormal monoclonal band, and the ratio of serum kappa and lambda light chains was also within the normal range (1.0; reference range, 0.26-1.65). 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy showed no definite DPD uptake in the myocardium. Cardiac magnetic resonance imaging could not be carried out because of the old-generation pacemaker leads. Coronary angiography was performed to exclude ischaemic cardiomyopathy, and a concomitant EMB was performed to investigate the possibility of unusual cardiomyopathy or chronic myocarditis. Coronary angiography revealed no significant stenosis in either the right or left coronary artery systems. Myocardial tissue of the right ventricle was obtained and analysed. Haematoxylin-eosin staining showed hypertrophy of myocytes (Figure 2A), and an electron microscopy revealed a disarrangement of mitochondrial cristae (Figure 2B), which were compatible with mitochondrial cardiomyopathy; Congo red staining was negative. Genetic testing was performed to identify genes related to cardiomyopathy. Although common mutations known to cause dilated cardiomyopathy, such as those in TTN, LMNA, MYH7, and TNNT2, were not found in next-generation sequencing, the m.3243A > G heterozygote mutation of the MT-TL1 gene was confirmed by Sanger sequencing (see Supplementary material online, Figure S1). However, no mutation of the MT-TL1 gene was identified in her mother. Of note, the patient never suffered from stroke-like episodes, serum lactic acid levels were found to be within the normal range (1.5 mmol/L; reference range, 0.5-2.2 mmol/L), and she never complained about headaches or recurrent vomiting episodes during the recent follow-ups.
The patient was prescribed guideline-directed medical treatment for heart failure, including sacubitril-valsartan (49/51 mg twice a day), carvedilol (12.5 mg twice a day), spironolactone (12.5 mg once daily), and dapagliflozin (10 mg once daily). Although upgrade to cardiac resynchronization therapy could be considered, given the high dependency on pacemaker, it was not proceeded because the patient was tolerable without exacerbation of any heart failure symptoms. In addition, 1 year after being on the guideline-directed medical treatment, a transthoracic echocardiography showed improved LV ejection fraction from 26 to 46%, but the LV wall remained thick. | atrioventricular block, cardiomyopathy, case report, heart failure with reduced ejection fraction, melas syndrome, mitochondrial disease | Not supported with pagination yet | null |
PMC8500390_01 | Female | 15 | A 15-year-old girl who was hit by a bus was admitted to our hospital. Initial examination revealed extensive skin and soft tissue defects on the lateral side of her right ankle. The talus was visualized through the wound, and the ankle joint showed marked instability (Figure 1A). A comminuted fracture of the distal fibula was revealed by plain radiography and computed tomography (Figure 1B and C). Surgical debridement was performed under general anesthesia. The damaged skin area was resected, resulting in a 10x10-cm defect (Figure 2). A distal fibula bone fragment was resected. The upper one-third of the anterior talofibular ligament (ATFL) remained; however, the lower two-thirds of the ATFL and the calcaneofibular ligament (CFL) was shaven off and disappeared from the distal fibula, along with the lateral part of the capsule. The distal half of the inferior extensor retinaculum remained. The talocrural joint was lax during the stress test and anterior drawer stress test; there was no damage to the articular cartilage on either the tibial or the talar side. Both peroneus longus and brevis tendons were severely crushed with segmental tear, and were resected. Kirschner wires were inserted from the proximal tibia to the talus and calcaneus for temporary fixation (Figure 1D). The wound was covered with a VAC (V.A.C. GranuFoam; KCI, Lane Cove, New South Wales, Australia).
Thirteen days after the initial debridement, a second surgery was performed. Under general anesthesia, the patient was placed in the semilateral position and a thigh tourniquet (250 mmHg) was applied. The gracilis tendon and semitendinosus tendon were harvested using a tendon stripper. First, we reconstructed the ATFL and CFL using a semitendinosus graft. Two parallel bone tunnels with a diameter of 3.5 mm were made at the footprints of the ATFL and CFL attachment sites of the distal fibula. The semitendinosus graft was passed through one bone tunnel in an anterior-to-posterior direction and through another tunnel in a posterior-to-anterior direction using a passing wire (Figure 3A and B). Another bone tunnel was made at the CFL footprint site in the calcaneus, and the distal end of the graft was inserted in the tunnel. Then, it was firmly fixed using a 4.75-mm interference screw (PEEK SwiveLock C; Arthrex Inc, Naples, FL). Additionally, a suture anchor (3.5 mm; Corkscrew FT; Arthrex Inc) was placed at the CFL footprint site of the calcaneus to reinforce the attachment site of the reconstructed CFL. Then, two perpendicular bone tunnels, merging in the talar neck, were made at the anterior border of the talar body. The proximal portion of the graft (ATFL) was passed through the tunnels, posteriorly to anteriorly, and then overlaid on itself (Figure 3B). With the ankle in 0 degrees of dorsiflexion and slight eversion, the proximal end of the graft was sutured on itself using nonabsorbable No. 2 FiberWire (Arthrex Inc.). After suturing the remnant of the ATFL on the graft, suture tape augmentation (InternalBrace; Arthrex Inc.) was performed. A 3.4-mm tunnel was made in the distal fibula, superior to the ATFL insertion, followed by 4.75 mm of tape. Another 3.4-mm tunnel was made in the talar neck, slightly distal to the graft tunnel. With the ankle in a neutral position, 3.5- and 4.75-mm suture anchors (PEEK SwiveLock; Arthrex Inc.) were loaded with suture tape (FiberTape; Arthrex Inc.) overlaying the reconstructed ATFL. To avoid overtensioning, a small hemostat was placed underneath the suture tape when inserting suture anchors. The inferior extensor retinaculum was then mobilized proximally and sutured onto the remaining fibular periosteum and ATFL with 3-0 Vicryl. Stability of the ankle was confirmed using anterior drawer and talar tilt tests. After reconstruction, the range of motion was maintained (dorsiflexion, 10 degrees; plantarflexion, 40 degrees).
Then, we reconstructed both the peroneus longus and brevis tendons. Two gracilis tendon grafts were prepared, and the proximal stumps of the peroneus tendons were sutured to the grafts with 3-0 Prolene using a Pulvertaft weave. While maintaining the foot in a neutral position, additional Pulvertaft weave suturing was performed between the distal stumps and grafts (Figure 4). The peroneal tendon sheath was repaired, and normal excursion of both peroneal tendons was confirmed. Finally, an 8x20-cm anterolateral thigh flap was harvested as a fasciocutaneous flap with subcutaneous perforators. The perforators were connected with anterior tibial vessels, and the wound was closed (Figure 5).
Postoperatively, the patient was fitted with a short leg splint. After 3 weeks, the splint was removed, and the ankle was completely free of immobilization, without any brace used. Physical therapy including proprioceptive training and active range of motion training was started. At 4 weeks, full weightbearing was permitted, and the patient returned to school. At final follow-up, two years after surgery, the patient returned to her preoperative level of work and sports activities, with no pain, no instability, and no loss of range of motion in her right ankle. | anatomic reconstruction, anterior talofibular ligament, calcaneofibular ligament, peroneal tendon, soft tissue defect | Not supported with pagination yet | null |
PMC5643106_01 | Female | 35 | A 35-year-old woman with no history of lung disease or occupational exposures and no active or passive cigarette smoking.
She had presented for evaluation of a chronic cough productive of voluminous secretions.
Over the previous 3 months, she had experienced episodic wheezing and dyspnea. During these episodes she often expectorated thick secretions which she described as resembling squid. Admitted to the pulmonary department she had no other respiratory or expiratory symptoms.
In clinical examination, heart rate was 96 bpm and polypnea was at 26 cpm, with condensation syndrome of all the left hemithorax. The chest-X ray showed a large opacity of the entire left hemithorax with attraction of the mediastinum element towards the opacity (Figure 1).
Computerised axial tomography of the chest confirmed a total left lung atelectasis without any pathological mediastinal node, oriented towards an endobronchial obstacle (Figure 2).
The x-pert MTB/RIF detects no DNA sequences specific for mycobacterium tuberculosis in specimen sputum. Flexible bronchoscopy demonstrated tenacious, thick, and sticky whitish secretions blocking the left stem bronchus.
This materiel was extracted, and inspection demonstrated a bronchial cast, whose pathological analysis revealed necrotic epithelial cells, some eosinophils, and Charcot-Leyden crystals (Figures 3(a) and 3(b)). Two days after bronchoscopy, the patient rejected more bronchial casts, and dyspnea improved. Control of chest-x-ray revealed complete left lung aeration (Figure 4).
The diagnosis of idiopathic plastic bronchitis was retained.
Despite several therapies with antimicrobials, glucocorticoids, and inhaled hypertonic saline, the patient continued to have extensive cast production over the next year.
She underwent repeat flexible bronchoscopy and small casts are rejected continually; she is always followed-up in the pulmonary department. | null | Not supported with pagination yet | null |
PMC3961060_01 | Female | 56 | The patient for this case report was a 56 year-old Caucasian woman with bilateral knee pain. Informed consent was obtained and the rights of the patient were protected. She reported a height of 166.37 cm and a weight of 106.14 kg. Her medical history was significant for osteoporosis, osteoarthritis, and multiple hernia operations. Medications used by the patient included Advil for pain (800 mg, twice per day), Calcium (1200 mg per day), Aspirin (81 mg per day), Nexium (20 mg per day), and vitamin D. Although she complained of shortness of breath with activity, there were no other signs suggesting that the patient would be inappropriate for physical therapy or would require referral back to her physician.
The physician provided a referral for physical therapy to evaluate and treat the medical diagnosis of bilateral knee pain. Per subjective report, the patient confirmed the presence of bilateral knee pain (left greater than right) with a duration of 5-6 years. The patient noted that the initial onset of her symptoms was insidious and that the pain, described as a diffuse aching pain, was located in the anterior aspect of both knees.
Prior to the most recent visit to her physician, and subsequent follow-up with physical therapy, the patient reported a significant increase in pain that she was trying to manage with over-the-counter pain medication. The patient noted that the pain had increased to a point that she could not stand from a sitting position without assistance and had difficulty walking and climbing stairs. Given the severity of the pain, the physician administered a Cortisone injection into both knees one week prior to beginning physical therapy. No specifics were provided regarding the dosage or the location of the injections. According to the patient, the injections relieved most of her pain and improved her function, but she was still taking multiple doses of Advil per day to manage her symptoms. At the time of the initial physical therapy evaluation, the patient reported 2/10 achy pain in the anterior aspect of both knees that worsened with sit to stand and stair climbing.
Prior to the examination, the patient completed the Activities of Daily Living Scale of the Knee Outcome Survey (KOS), a reliable and valid outcome measure of knee pain and function for a variety of diagnoses, including patellofemoral pain. Scores on the KOS range from 0-100 (Standard Error of Measurement and Minimum Detectable Change (MDC67), 5.15) with 0 representing a complete loss of function and 100 representing no loss of function with complete absence of symptoms. When the patient initially completed this form, she obtained a score of 50, suggesting a 50% loss of function. On a separate subjective question that has not been fully validated in the literature, the patient rated her current level of function during daily activities as 30 out of 100, with 100 being the level of function prior to pain or injury. Thus, despite the reported success of the injections, the patient was still documenting significant functional limitation as a result of her knee pain.
According to the patient, the anterior knee pain was still limiting her ability to perform work, household, and recreational activities. The patient was a registered nurse who worked in a physician's clinic. Her job required both desk work and patient care. Therefore, the patient needed to transition from sitting to standing multiple times per day. Additionally, the patient lived in a multi-story home. Thus, the patient had to ascend and descend the stairs several times per day. Both of these activities seemed to contribute to the persistence of her anterior knee pain. Therefore, the patient felt limited in the amount of exercise that she could perform to lose weight and maintain optimal health.
Ultimately, the patient's goals for physical therapy were to maintain or to improve upon the progress achieved from the injections, to decrease her need for pain relieving medication, to build strength and endurance in her lower extremities, and to improve her tolerance for walking, particularly for fitness. The patient was motivated to participate in physical therapy in order to optimize her tolerance of functional activities and to improve her overall health.
Following the subjective history, an objective examination was performed in order to identify specific movement and postural factors that might be contributing to the patient's pain and to quantify measures of muscle performance, range of motion, and alignment (table 1). Visual observation was first used to determine postural alignment in standing. The patient was noted to have bilateral hip adduction with medial rotation of the femurs. In addition, the patient stood with her knees slightly flexed. Inspection of her patellar alignment suggested that her patella was superiorly displaced (figure 1).
Therefore, a more quantitative assessment of her patella alignment was performed based on the Insall-Salvati (IS) ratio,which compares the length of the patellar tendon (TL) to the height of the patella (PL).. proposed that the ratio between patellar tendon length and patella height should normally be one and that two standard deviations (SD) above or below the mean should be considered abnormal. Thus, patients that have a TL/PL ratio of 1.2 or greater (1 + 2 SD) are characterized as having PA. To screen the current patient for PA , the length of the patella tendon was measured using the inferior pole of the patella and the tibial tubercle as landmarks. The height of the patella was measured using the superior margin and the inferior pole of the patella as landmarks. The values were then compared to determine the IS ratio (figure 2).
However, because clinical measures for patella alta have been deemed unreliable, the clinical measurements taken were confirmed with more specific measurements of the lateral radiograph (figure 2) that were provided by the referring physician. To assess for PA on the lateral radiograph provided, the length of the patella tendon was compared to the diagonal height of the patella. While the landmarks used to assess patellar tendon length were the same as those that were palpated clinically, the landmarks used to assess patella height were different. Using the radiograph, patella height was measured from the posterior, superior margin of the patella to the anterior, inferior pole of the patella. According to, measurement of patella alta using a lateral radiograph and the landmarks described has been shown to be associated with minimal interobserver error (0.044 +- 0.047 with a Spearman's rank correlation coefficient of 0.86). Based on the calculated ratio values listed in table 2, this patient appeared to demonstrate bilateral patella alta that was worse on the left than on the right.
While the patient was standing, she was instructed to perform bilateral hip and knee flexion (partial squat). The patient reported pain at end-range with this movement. Passive correction of femoral adduction and rotation did not significantly decrease the symptoms reported. However, with a manual glide of the patella in an inferior direction, the patient did note a reduction of pain. This correction was provided to the patient in an effort to decrease the resting height of the patella in the trochlear groove prior to movement.
In sitting, the patient was first asked to actively extend each knee in order to assess her movement strategy. During these movements, the patient reported increased pain, and significant crepitus was noted. Manual gliding was performed to theoretically modify the resting height of the patella before knee extension was performed, resulting in decreased pain in both knees. The manual glide provided at the patella did not prevent the superior translation of the patella that might normally occur with quadriceps recruitment. Subsequent quadriceps strength testing was not performed because of the potential for pain
Palpation of relevant structures around each of the knees was also performed in sitting. Specifically, the patient reported no change in symptoms in either knee with palpation of the quadriceps and patellar tendons, the medial and lateral joint lines, or the infrapatellar fat pad. Additionally, there was no evidence of localized inflammation of the quadriceps or patellar tendons such as swelling or increased heat.
Active range of motion of the knee was assessed in supine. Knee flexion was 120 degrees bilaterally and knee extension was -5 degrees bilaterally. The patient reported anterior knee pain and stiffness at the end of knee flexion range of motion. Accessory motion of the patellofemoral joint was assessed and found to be limited bilaterally, but pain free. Accessory motion of the tibiofemoral joint was not assessed. Special tests to assess ligamentous and meniscal integrity in supine were not performed because the patient's history was not suggestive of either impairment.
In left and right side-lying, the patient had slight medial rotation of the top leg on both sides. The length of the TFL-ITB was tested using the modified Ober test, in which the knee was flexed to 90 degrees. The test was positive for impaired length of the TFL-ITB. The strength of the posterior gluteus medius was tested using standard manual muscle testing procedures as described by; the test results were 3/5 for both the left and the right.
In prone, no specific postural abnormalities were noted. Strength testing of the gluteus maximus was not performed secondary to the concern regarding her multiple hernia operations and the potential risk of injury to her lower back with end range hip extension. Next, functional activities such as sitting to standing, sleeping, gait, and stair climbing were evaluated. Transitioning from sitting to standing, the patient required upper extremity support and noted significant pain in her anterior knee. To modify her symptoms the patient was first cued to transition from sitting to standing at the edge of her chair. With this correction, the patient was able to stand more easily, but the anterior knee pain was unchanged. Therefore, using the same rationale as described previously, a force was applied manually to the patella in an inferior direction during the sit-to-stand motion, which resulted in a significant reduction of pain.
When asked to demonstrate her sleeping position, the patient assumed a side-lying position with her top lower extremity resting in hip flexion and medial rotation. Cues were provided to correct her sleeping position in order to determine whether the patient was more or less comfortable in side-lying in response to changes in alignment. When a pillow was placed between her lower extremities, the patient did, in fact, report increased comfort, but, again, no specific changes in knee pain were noted.
During the examination, the patient did not report pain during walking. However, excessive medial femoral rotation was observed during the stance phase of gait from foot flat to push-off. No corrections were provided at the time of the examination because her gait was not painful. By contrast, ascending and descending the stairs did increase her pain. It was not possible to provide a manual glide to the patella during this task, therefore, no conclusions could be made regarding the possible effects of patellar mal-alignment.
The patient was able to complete the examination described above with only a minimal increase in her symptoms. A diagnosis was determined based on these examination findings, and it was deemed safe to continue the initial visit and to provide appropriate treatment.
The examination findings were consistent with a diagnosis of Patellar Tracking Syndrome with Superior glide (APPENDIX A). This diagnosis describes anterior knee pain that is associated with an impaired relationship between the patella and the femur, which, in this case, was patella alta. The key finding supporting this diagnosis was the consistent decrease in pain associated with manual, inferior correction of the patella. In addition, the patient described diffuse anterior knee pain that was not specific to the quadriceps tendon, the patellar tendon, or the tibiofemoral joint. Pain underneath or around the patella is considered indicative of a patellar alignment and tracking problem, particularly when the pain is consistently exacerbated with activities such as, stair climbing, sitting to standing, and partial squat. Finally, open chain activities such as knee extension in sitting were also painful, which supports the diagnosis of Patella Tracking Syndrome with Superior Glide because knee extension from 90 degrees of knee flexion to 25 degrees can increase patellofemoral joint reaction force. Because patella alta seems to be associated with a decrease in the size of the contact area between the patella and the femur, any significant increase in the joint reaction force, such as that which occurs with active knee extension, could significantly change the overall contact stress within the patellofemoral joint.
The patient was seen for 11 visits, including the initial evaluation, over a period of 6 months. The extended duration of physical therapy was necessary to accommodate the patient's travel schedule, as well as, to provide a mechanism for which to monitor the long-term success of treatment. During this time period, the emphasis of the treatment provided to the patient was on the correction of the positional fault of the patella in both lower extremities using tape. However, to improve the effectiveness of the taping method used to correct patellar alignment, treatment also addressed the correction of the patient's movement impairments with exercise prescription, as well as, functional training for the management of symptoms throughout the day.
Following the initial evaluation, four exercises were prescribed to address issues with regards to muscle length and motor recruitment (table 3). These exercises were performed by the patient at subsequent visits for review, and corrections were provided to the patient as needed.
In an attempt to reduce the superior displacement of the patella, the patient was also instructed to perform patellar mobilizations in an inferior direction as illustrated by. The patient was instructed to perform three sustained inferior patellar glides on both knees for 30 seconds each. The patient was not educated on specific mobilization grades. Rather, she was instructed to mobilize the patella within a pain free range.
Exercises specific to the impairments found during an examination are certainly an important component of treatment. However, unless the patient modifies his or her performance of daily activities that are contributing to pain, the long-term success of a home exercise program could be limited. In the present case, transitioning from sitting to standing and stair climbing were contributing to the symptoms that she was experiencing. Therefore, the patient was educated on specific compensatory and component strategies of movement to reduce the amount of patellofemoral stress experienced during these daily activities (table 4).
Given the degree of her patella alta, exercises and education were not sufficient in reducing her pain to a tolerable level. According to, some form of external support is often needed to reduce the physical tissue stress at a particular joint and to control symptoms. Taping is one form of support often employed by physical therapists to provide stabilization to a joint or assistance to a particular movement. In this case, Leukotape was used to provide stabilization to the patella in order to reduce the stress associated with the superior displacement noted. Prior to taping, the patient was educated on the purpose of the tape, doffing instructions, and appropriate skin care following removal. Because the patient believed she might be allergic to the tape, she was instructed, after the initial examination, to apply a test strip of tape and to monitor the skin for itching, redness, or rash.
During her first follow-up visit, the patient reported that she did not experience an adverse skin reaction secondary to the test strip of tape. The patient, therefore, consented to the taping intervention and tape was applied to both knees. For this patient, a novel method of taping was employed. Tape was applied in an inverted "U" pattern over the anterior knee to apply an inferiorly directed force at the superior margin of the patella.
The procedures used to apply the tape in this fashion were as follows. The patient was positioned in long-sitting and the knee was supported by a small towel roll. Cover-roll was applied first to protect the skin from the adhesive of the Leukotape. To apply the Leukotape, a strip of tape approximately 12 inches long was positioned at the superior margin and was affixed in such a manner that half of the width of the tape was on the patella while the other half of the tape was over the quadriceps tendon. An inferior force was then applied through the tape to the patella with care taken not to compress the patella within the trochlear groove. As the inferior force was applied, the tape was affixed on either side of the knee forming an inverted "U" shape over the patella (figures 2 and 3). Three to four additional strips of Leukotape were applied in a staggered fashion to increase the stability of the support. Initially, the patient was taped bilaterally.
As the treatment progressed and the tape was deemed successful at reducing her symptoms, the patient was instructed how to tape her knees independently. The same method of taping described above was used by the patient to self-tape. Self-taping allowed the patient to provide a more consistent, inferior force to the patella to help relieve her symptoms. The patient was instructed to apply the tape unilaterally and to alternate which knee was taped in order to manage her pain bilaterally and to protect her skin. Periodically, the therapist reviewed the tape applied by the patient to ensure that the taping procedure was being performed correctly. The patient continued self-taping for both knees for the duration of therapy, and was instructed to tape herself as needed following discharge.
The final component of the intervention provided to the patient was education regarding the initiation and progression of a conditioning program for general health and fitness. As the patient progressed in therapy, she was instructed on the performance of a walking program to improve her cardiovascular health while minimizing her symptoms. Because the patient had access to a pool, she was advised about the potential benefits of water exercise and cross-training and was instructed to use the pool 1 to 2 times per week. When unable to exercise in pool, the patient was given the alternative of using a stationary bike instead.
During the course of therapy, the patient demonstrated compliance with taping, as well as, the prescribed home exercises and her conditioning program. Ultimately, the patient was motivated to improve and to address her health and weight concerns with appropriate exercise.
To summarize patient improvement over the time period for which she was seen for physical therapy, a novel assessment of patient progress was developed (figure 5). Specifically, seven indicators of patient progress chosen by the authors were obtained from the patient chart. These indicators were assessed at 6 different time points throughout the duration of treatment. All indictors, excluding whether the pain was constant or intermittent and the ability to participate in physical activity such as walking and swimming, were judged relative to baseline measures at the initial evaluation. Other indicators of progress were pain severity, pain with functional activity as reported by the patient, medication use, Knee Outcome Survey score, and global level of function as reported by the patient on the Knee Outcome Survey.
For each of the five indicators that were assessed relative to baseline measures a score was provided for each patient visit. If the indicator of progress was either not assessed or unchanged relative to baseline, a score of 0 was assigned. If the indicator of progress had improved relative to baseline a score of 1 was assigned. Conversely, if the indicator of progress had worsened, a score of -1 was assigned. For the indicators of progress that were not compared to baseline, a score of 0 or 1 was assigned according to the following method. If the pain was described as constant, a score of 0 was assigned whereas if the pain was described as intermittent, a score of 1 was assigned. Likewise, if the patient was unable to participate in physical exercise such as walking or swimming, a score of 0 was assigned. If the patient reported participation in physical exercise such as walking or swimming, a score of 1 was assigned. Therefore, for each visit assessed, the patient could receive a cumulative score representing patient progress as high as 7 or as low as -5. When applying this novel assessment of patient progress, it is clear that the patient did steadily improve before worsening at visit 8. Assessment of these same indicators of progress at discharge also demonstrated significant progress relative to both visit 8 and baseline measurements. A more detailed description of specific patient progress, including the rationale for the patient's worsened status at visit 8 follows.
After initiating patella taping, the patient reported feeling "100% better" by the third visit, which was approximately four weeks after the initial evaluation. During the 3rd visit, the patient noted that the transition from sitting to standing was easier and less painful and that the tape specifically improved her ability to ascend the stairs. Therefore, as noted previously, the patient was provided instructions for self-taping. By the 5th visit, the patient reported minimal pain in both knees (1-2/10 pain that was not constant) and improvement in all functional activities. The patient also noted that she had reduced her use of pain medication to 800 mg of Advil as needed. Because of the progress demonstrated to this point, the patient was instructed to begin the conditioning exercises as described previously and the frequency of physical therapy was reduced to one visit every two weeks.
The patient's symptoms, however, worsened by her 6th visit. She reported a general increase in pain with walking, sitting to standing, and stair climbing. The patient attributed her symptoms to an increase in her activity level. She was walking at the gym more frequently than had been recommended. Therefore, the patient was provided instructions regarding activity moderation and aquatic exercise to limit the cumulative stress on the patellofemoral joint.
By the 7th visit, taping and moderate exercise enabled the patient to manage her symptoms more appropriately. In fact, the patient reported that her pain was only minimal and that the taping was helpful. Thus, the patient was instructed to continue her home program of taping and exercise as prescribed and to return in 2-3 weeks for evaluation and follow-up.
When the patient returned for her 8th visit, she noted that she had progressively worsened. She was now having more pain with the transition from sitting to standing and with walking. Though she was compliant with the home exercise program and her conditioning routine (walking and swimming), the pain was starting to limit more of her functional abilities. At this point, the tape was no longer working to relieve her symptoms. Her regression was confirmed by the change in her KOS score. Upon re-evaluation at her 8th visit, the patient only scored a 38.5 on her Activities of Daily Living Scale and rated her level of function at 20% of normal.
The patient could not attribute her increase in symptoms to any specific activity or event. However, it was observed, that the tape on the patient's knee had been applied incorrectly. The tape was positioned superior to the margin of the patella around the distal quadriceps muscle and was providing no stabilization force (figure 6). The self-taping being performed by the patient was ineffective. Therefore, the patient was re-instructed on the appropriate taping technique and was asked to follow-up in one week.
Upon return to physical therapy after one week, the patient reported a significant improvement in her symptoms with the correction of the taping application. Indeed, the patient reported decreased pain with sit to stand and noted that she was able to walk approximately one mile on the track with minimal difficulty. Visual observation of the tape applied by the patient revealed that she had positioned the tape correctly. The patient was instructed to gradually progress her conditioning program, continue with the taping, and follow-up in one month.
Despite having to cope with an episode of pneumonia, the patient reported at the one-month follow-up (10th visit) that she had been able to manage her pain with the taping and exercise. In fact, the patient noted that she was having minimal difficulty with walking and was able to actively participate in a previously planned tour to Washington D.C. Her average pain was reported to be a 1-2/10 and she noted decreased use of pain medication (actual dosage was not provided). Stair climbing was still challenging, but the patient stated that it was easier relative to her baseline level of function at the initial evaluation. At this time, the patient completed a 3rd KOS. She scored a 56 on the Activities of Daily Living Scale and rated her level of function at 70% of normal (table 5).
In addition to the administration of the KOS, many of the tests assessed during the initial evaluation were re-evaluated at this visit (10th visit). Based on clinical measurements, the alignment of the patella had not changed significantly. The IS ratio calculated for the alignment of her right patella was 1.31 while the IS ratio for her left patella was 1.4. The patient did, however, demonstrate improvement in posterior gluteus medius strength to 3+/5 bilaterally and increased knee flexion range of motion (128 degrees on the right and 125 degrees on the left). Knee extension range of motion was not reassessed. Functionally, the patient reported minimal pain and no obvious movement impairments with sit to stand and gait. Stair climbing was first assessed without tape and was found to be painful. With the application of the tape to provide an inferior force to the patella, the patient reported a significant decrease in symptoms. Based on the results of this re-evaluation, it was clear that the patient had improved relative to her baseline level and that she was able to effectively manage her symptoms with tape and exercise.
The patient returned to therapy for follow-up two weeks later. During this visit, the patient subjectively noted that pain was no longer limiting function. Furthermore, she was walking 3-4 times per week without pain and was exercising in the pool 1-2 times per week. Taping and exercise were reviewed and the patient was discharged with instructions to continue her prescribed therapy. | null | Not supported with pagination yet | null |
PMC10043165_01 | Female | 66 | A 66-year-old woman presented with a 1-month history of a painful isolated mass on the inside of the left calf. She also complained of bilateral numbness in her toes. A history of contact with patients with suspected TB could be traced: her father had had pulmonary TB 10 years previously, and her daughter had had tuberculous pleurisy 7 years previously. She was in good general condition and did not complain of systemic symptoms such as night sweats, weight loss, anorexia, fatigue, or intermittent fever. Physical examination revealed a tender mass with irregular indistinct borders in her left calf. Movement was severely restricted by knee pain. She had a slight decrease in sensation and swelling of the lower extremities. The local temperature was not elevated, and the skin over the mass was normal. No obvious mass was palpable on the right leg. Further clinical examinations, including hemogram, erythrocyte sedimentation rate (ESR), procalcitonin test (PCT), liver and renal function tests, antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), fungal G-test, and tumor marker levels, returned results within normal limits. Serological rheumatoid factor (RF) was elevated to 33.8 iu/ml (reference range: up to 15 iu/ml), serological high sensitivity C-reactive protein (CRP) waselevated to 7.48 mg/L (reference range: up to 3 mg/L), and antistreptolysin O (ASO) was positive. Tuberculin antibody IgG, IgM, gamma-interferon release test, purified protein derivative (PPD) skin test, acid-fast bacilli smear, and tissue culture of sputum were negative. Electromyography (EMG) indicated reduced motor and sensory nerve conduction velocity in the lower limbs (MCV: 25.8-33.1 m/s, SCV: 0-34.3 m/s), accompanied by decreased compound motor action potential (CMAP: 1.6-12.1 mV) and sensory nerve action potential amplitude (SNAP: 0-2.1 uV). Distal motor latency and F wave were normal. The duration and amplitude of motor unit potential (MUP) were increased, without spontaneous activity, indicating extensive chronic neurogenic lesions.
Chest computed tomography (CT) of case 1 revealed scattered bilateral inflammatory changes in the inferior lobes of both lungs and multiple nodular thickening on both sides of the pleura. Bilateral ultrasound of the calves suggested a 50 x 16-mm hypoechoic lesion in the left soleus muscle (Figure 1A) and a 43 x 6-mm hypoechoic lesion in the medial head of the gastrocnemius muscle. Additionally, 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG-PETCT) revealed multiple hypermetabolic lesions, which involved the left soleus muscle, the left musculus fibularis longus, the right soleus muscle, and the tibialis anterior muscle. The largest lesion was located on the middle of the left soleus muscle measuring 33.8 x 20 x 42 mm, and the maximum standardized uptake value (SUVmax) was 15.9 (Figure 1B). Magnetic resonance imaging (MRI) examination showed abnormal mass signals involving the inner front edge of the gastrocnemius muscle. The lesion was enhanced by gadolinium on the T1-weighted turbo spin-echo (T1W-TSE) image, and T2-weighted spectral presaturation attenuated inversion recovery (T2W-SPAIR) showed a hyperintense mass. There was a similar lesion in the gastrocnemius muscle of the right leg (Figures 1C, D). Pelvis and lumbar spine MRI showed mild lumbar disk herniation, with no other abnormal findings.
A muscle biopsy of the left gastrocnemius was performed in case 1; the result showed multiple nodular epithelioid granulomas embedded among the muscle fibers. Caseous necrosis was found under the microscope (Figure 1G). Microscopic examination for acid-fast bacilli stain and cytokeratin (AE1/AE3) was completely negative. CD3, CD31, CD34, desmin, Kp1, and PGM1 staining were weakly positive. The Ki67 labeling index was low (10%). PCR for the mycobacterium tuberculosis complex in blood, urine, sputum, and paraffin-embedded samples from case 1 returned negative results; however, the result was positive in frozen sections of muscles. A diagnosis of MT was considered in case 1, despite the fact that all the tests used for diagnosis of TB were negative, with the exceptions of PCR and histopathology. | acid-fast bacilli stain, muscular mass, muscular tuberculosis, polymerase chain reaction, tuberculosis | Not supported with pagination yet | null |
PMC10043165_02 | Female | 50 | A 50-year-old woman presented with a mass in the right calf for 4 months. There were no symptoms of cough or weight loss, and no history of intramuscular injection at the site concerned or of any contact with TB. Physical examination revealed an indurated nodule with no tenderness or elevation of local temperature, about 8 x 5 cm in size. The borders of mass were not well-demarcated. There was no abnormality of distal vascularity or sensation, and no limitation of movement. Laboratory tests revealed a normal blood count, and liver function tests, ASO titers, and renal functions were not deranged. An extensive laboratory workup, including ANA, ANCA, CRP, tumor marker levels, thyroid function tests, and inflammatory markers, returned results within normal limits. The outcomes of several infection tests for syphilis, hepatitis B, hepatitis C, and HIV were negative.
Ultrasound of the right calf was performed in case 2 and suggested a hypoechoic lesion. The patient in case 2 also underwent musculoskeletal MRI examination, and the result showed similar lesions to case 1 in the soleus muscle and medial posterior part of the right tibia and fibula (Figures 1E, F). According to radiological imaging findings, both patients had other painless muscular nodules at multiple sites throughout their entire bodies.
Resections and histopathologic observations of lesions were performed in case 2. Granulomatous inflammation, mainly composed of epithelioid histiocytes and Langerhans giant cells, was observed under the microscope (Figure 1H). Histopathologic examination showed the presence of non-necrotizing epithelioid granulomas compatible with TB. Immunohistochemistry against CD4/CD8, MHC-I, and MAC (C5b9) was negative. Moreover, the acid-fast bacilli stain was negative. PCR for TB was positive in case 2 in paraffin-embedded and frozen sections of muscles. A diagnosis of MT was considered in case 2, despite the lack of detectable focus of tubercular infection except in the PCR and histopathology results.
Many differential diagnoses were considered in both cases, including deep vein thrombosis, a soft tissue tumor, or a pyogenic abscess. Based on the diagnosis of MT, the patients in cases 1 and 2 were both prescribed standard oral antituberculosis treatment with four drugs, namely, isoniazid, rifampicin, ethambutol, and pyrazinamide, for 2 months. After treatment, the patients' symptoms were relieved, and the nodules in the calves appeared to decrease in size. Further courses of isoniazid and rifampicin were administered. At the time of writing, the patients are undergoing follow-up. | acid-fast bacilli stain, muscular mass, muscular tuberculosis, polymerase chain reaction, tuberculosis | Not supported with pagination yet | null |
PMC6263306_01 | Male | 35 | The male, 35-year-old patient was admitted to hospital with a tender and swollen left ankle, pain and limited movements in the shoulders, as well as low back pain (LBP) and pain in the area around the lumbar vertebrae (L1-L4). Three intramuscular injections with betamethasone were made before admission to the hospital.
The laboratory results were as follows: haemoglobin 139 g/l (n: 135-180); erythrocytes 4.6 x 1012 (n: 4.4-5.9); leucocytes 11.76 x 109 (n: 3.5-10.5); platelets 166 x 109 (n: 130-360); C-reactive protein 102 mg/l (< 5 mg/l); erythrocyte sedimentation rate (ESR) 78 mm/h (n: < 15 mm/h); AspAT 81 U/l (n: < 32 U/l); AlAT 49 U/l (n: < 33 U/l); GGTP 111 U/l (n: < 40 U/l); AP 141 U/l (n: < 105 U/l); total bilirubin 31.9 mumol/l (n: < 21 mumol/l); direct bilirubin 12.3 mumol/l(n: < 8.5 mumol/l). Also laboratory tests revealed rheumatoid factor positivity for IgM, IgA and IgG classes of immunoglobulin (n: 243.8; 182.1 and 95.1 U/ml respectively), as well as anti-citrullinated peptide antibodies (ACPA) 93.6 U (normal range < 20 U), and anti-mutated citrullinated peptide antibody (anti-MCV) 20.8 U/ml (normal range < 20 U/ml). HLA-B27 was negative.
Ultrasound examination of the left ankle showed synovitis with positive power Doppler signal. Ultrasound of the small joints of the hands did not present pathological features. X-ray of sacroiliac joints revealed a rough right sacroiliac joint (Fig. 1). X-ray of ankles, hands and the thoracolumbar part of the spine with sacroiliac joints did not show pathological changes.
Cultures (blood culture, sterile urine) were negative for infectious organisms. Blood serological tests for Chlamydia trachomatis antibodies (IgG, IgM, IgA class) and polymerase chain reaction (PCR) testing for Chlamydia trachomatis in a urine specimen were negative. The X-ray of the lungs and the ultrasound examination of the abdomen also did not reveal abnormalities.
The patient had no comorbidities or family history of arthritis, but he was diagnosed with hepatitis A virus in November 2016.
Analysis of symptoms and additional tests were taken into consideration diagnosis as follows:
seronegative spondyloarthropathy,
rheumatoid arthritis,
undifferentiated arthritis.
Seronegative spondyloarthropathy (SpA) was initially diagnosed - inflammatory back pain, onset before 45 years of age, in the X-ray image of the right sacroiliac joint there was a suggestion of sacroiliitis, despite the absence of the HLA-B27 antigen. MRI of the spine or sacroiliac joints had not been performed at this stage.
The patient did not fulfil the criteria for classification (ACR/EULAR classification criteria from 2010) of rheumatoid arthritis (RA); he had ACPA antibodies and rheumatoid factor (RF), but had only one joint involvement.
Undifferentiated arthritis was considered but LBP and arthritis strongly suggested an early stage of SpA, even though HLA-B27 was not present.
Corticosteroid was applied locally in the left ankle. Therapy with sulfasalazine 2 g/daily and a non-steroidal anti-inflammatory drug (NSAID) was initiated.
Also the patient consulted a gastroenterologist who concluded that the patient had protracted hepatitis A infection. Therapy with ademetionine 500 mg twice daily was prescribed.
One month later the patient presented to the rheumatologist with fever, low back pain, pain in vertebrae and spinous processes located in the lumbar region of the spine. Laboratory tests showed high inflammatory serum markers: ESR 84 mm/h and CRP 51.2 mg/l. Computed tomography of the spine demonstrated destruction of the L1-L2 disk space with the adjacent L1 and L2 vertebral bodies (the image corresponded with spondylodiscitis), as the contiguous iliopsoas muscle was affected (Fig. 2).
Blood cultures were negative. The Mantoux test and QuantiFERON (QFT) test for tuberculosis or latent tuberculosis infection were performed and were negative. Sulfasalazine treatment was discontinued. Therapy with ceftriaxone 4 g/daily and lincomycin 600 mg three times daily intravenous application was initiated. The antibiotic therapy was discontinued after 21 days after MRI examination of the lumbar spine, which showed destruction of the L1-L2 and L3-L4 disk spaces with the adjacent vertebral bodies. The T2-weighted MR image demonstrated discitis and osteomyelitis persisting as an abscess in the structure of right iliopsoas muscle (Fig. 3).
Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the next three consecutive blood cultures. The patient consulted a neurosurgeon who stated that there was considered an indication for surgery if the patient did not show improvement on treatment with targeted antibiotics. Antibiotic therapy with teicoplanin 400 mg daily and levofloxacin 500 mg daily intravenous application was started and was applied for six consecutive weeks. Rifampicin 300 mg daily was prescribed for three months. Intravenous immunoglobulins were applied in a dose of 400 mg/kg in three contiguous months.
After the end of the antibiotic course the laboratory results were as follows: haemoglobin 161 g/l (n: 135-180); erythrocytes 5.25 x 1012 (n: 4.4-5.9); leucocytes 10.5 x 109 (n: 3.5-10.5); platelets 181 x 109 (n: 130-360); C-reactive protein 4.6 mg/l (n: < 5 mg/l); erythrocyte sedimentation rate (ESR) 28 mm/h (n: < 15 mm/h); AspAT 39 U/l (n: < 32 U/l); AlAT 22 U/l (n: < 33 U/l); GGTP 69 U/l (n: < 40 U/l); AP 105 U/l (n: < 105 U/l); total bilirubin 20.5 mumol/l (n: < 21 mumol/l); direct bilirubin 11.9 mumol/l (< 8.5 mumol/l). There was no deterioration of the liver function test, but the liver enzymes and bilirubin remaining elevated.
Three months later control MRI was performed and visualized in the structure of the bodies of L1, L2, L3, L4 vertebrae and the adjacent disc surfaces irregular shaped areas with characteristic bone marrow oedema and fat bone marrow transformation. The height of the L1-L2, L3-L4 vertebrae decreased with the pathologically increased signal intensity. Zones of changed signal intensity were visualized in the structure of the two psoas muscles, at level L1-L2, with high signal intensity in T2 dependent sequences (post-inflammatory changes). | staphylococcus aureus, infectious spondylodiscitis, magnetic resonance tomography | Not supported with pagination yet | null |
PMC4706269_01 | Male | 46 | On April 30, 2014, a 46-year-old male patient was admitted to the gastroenterology department with dyspepsia, abdominal pain, vomiting, and a 4 kg weight loss. The patient had previously undergone an appendectomy and abdominal abscess debridement for right abdominal pain and fever in January 2008. Seven months after the operation, he underwent a resection of the ileocecum for a spontaneous perforation that occurred in August 2008. The pathological diagnosis was ITB and the patient underwent antituberculosis therapy for 1 year.
The patient was hospitalized for right lower quarter pain on April 30, 2014. He had a fever, and physical examination revealed a bulge on the right lower abdomen, obvious tenderness, no fluctuation, no rebound pain, and muscle tonus. The laboratory results for the patient revealed the following: a white blood cell count of 11.77 x 109/L (normal range 4-11 x 109/L), thrombocytosis (platelet concentration of 469 x 109/L, normal range 100-300 x 109/L), and a fecal occult blood test of 1+. All other tests were normal. The computer tomography (CT) scans showed a segmental and irregular thickening of the anastomosis, ascending colon, and hepatic flexure with thickened mesenteric fat; dense shadows of anastomosis; and multiple stripes, nodes, exudation, and bubbles. Colonoscopy revealed a severe hyperemia and edema of mucosa in the anastomosis that was associated with inflammation, a fistulous opening, mucopurulent exudate, and multiple deep ulcers. The pathology showed mucosal chronic inflammation associated with ulcers and acute inflammation, moderate atypical hyperplasia of the glands, and a crypt abscess. The patient became asymptomatic after anti-inflammatory and nutritional support therapy.
The patient was hospitalized for right lower quarter pain again on June 15, 2014. His vital signs were normal and physical examination revealed a mass on the right lower abdomen (5 x 4 cm in size). All laboratory tests were normal. The CT scan showed the wall thickness of the right colon and the anastomosis, and the gas shadow in swelling soft tissue of the right lower abdominal wall (Figure 1). A right hemicolectomy was performed after the preparation because of the persistent right lower abdominal mass. Macroscopic histopathology showed that the intestinal wall was thickened with luminal narrowing (Figure 2).
The pathology after the operation showed colic mucosal ulceration along with transmural inflammation, mixed inflammatory infiltrate, and granuloma (ie, lymph cells and plasmacytes infiltrated the abdominal wall, and a granulomatous change occurred in the muscular layer) (Figure 3). The Ziehl-Neelson stain for acid-fast bacilli was negative. As the time between the first diagnosis and the second diagnosis was 6 years, 2 of our pathology experts rechecked the pathological data with the permission of the patient and the hospital. Both experts considered that the pathological diagnosis should be CD rather than ITB. Ultimately, we made a diagnosis of CD, which is indicative of the pathological changes and the history of recurrent intestinal fistula. According to the patient's CDAI, he was treated with infliximab. At the time of the 8-month follow-up, the patient had remained in complete remission and made a good recovery. | null | Not supported with pagination yet | null |
PMC5714067_01 | Female | 22 | We report a case of interlobar CD, treated successfully with surgery and adjuvant radiotherapy. A 22-year-old woman, asymptomatic, non-smoker, without history of any chronic illness (including tuberculosis) was admitted to thoracic surgery department due to incidental discovery of right parahilar tumour on prophylactic chest radiograph (Figure 1). No evidence of the lesion was present 3 years earlier. There are no clear indications why chest radiographs were ordered by family physician and occupational specialist at that time. Bronchoscopy did not reveal any endobronchial abnormalities, and the bronchioalveolar lavage cytology was normal. Pulmonary function and routine blood tests were within normal range. Chest CT scan demonstrated well-circumscribed, contrast-enhancing tumour in the right horizontal fissure, tightly adherent to branches of pulmonary artery and upper pulmonary vein (Figure 1). No mediastinal lymphadenopathy, any other intrapulmonary or intraabdominal lesions were detected.
Since malignancy could not be ruled out, the right-sided video-assisted thoracoscopy (VATS) and biopsy of the tumour was planned. VATS was performed using three troacars. Inspection of the right hemithorax revealed relatively well-circumscribed, encapsulated solitary mass in horizontal fissure tightly adherent to adjacent interlobar vasculature. Tumour showed hypervascular features, and despite careful dissection, noticeable diffuse bleeding occurred. Complete macroscopic excision of the tumour was considered to be possible, but too risky thoracoscopically. Conversion to conventional axillary thoracotomy was made and tumour excised. Total blood loss was approximately 300 mL. The postoperative period was uneventful and the patient was discharged home on the fifth postoperative day. A pathological examination revealed a 2.5 x 2.5 x 2 cm3 tumour with bright-rose colouration, morphologically consistent with hyaline vascular type of CD without any evidence of malignant transformation (Figure 2). Although the tumour was macroscopically removed, we were doubtful about the radicality of the operation. Margins of apparently tumour-free tissue around the lesion was hard to assess microscopically due to avoidance of extended resection; thus, there was a risk of potential R1 - resection. Because of the tight adherence to pulmonary vessels, as well as to lung parenchyma and possible invasive nature of the tumour, the pulmonary oncology council suggested adjuvant radiation therapy. The patient received three-dimensional conformal radiotherapy to the site of operation in once daily 2 Gy fractions to cumulative radiation dose of 44 Gy. During 6-year follow-up period, the patient is free from recurrence. No complication from surgery or adjuvant radiotherapy has occurred. | castleman disease, interlobar, radiotherapy, surgery | Not supported with pagination yet | null |
PMC9779991_01 | Female | 5 | A 5-year-old female from nonconsanguineous marriage, with a medical history of snoring without sleep apnea, had presented asthenia, gingival bleeding, and diffuse bone pain evolving for three months, without associated fever. Before admission to our hospital, the patient had visited a general practitioner who ordered blood tests. Initial cell blood count showed bicytopenia (microcytic hypochromic anemia at 10.1 g/dL and thrombocytopenia at 100 G/L) with low reticulocytes at 70250/mm3. The patient was referred to the hospital for further investigations. Physical examination showed pallor, gingival hypertrophy, and petechiae over the abdomen. Palpation revealed painless and bilateral cervical lymphadenopathy, without splenomegaly or hepatomegaly. The skeletal examination showed several bony nodules on the forehead, mandible, wrists, and knees.
Cell blood count revealed microcytic hypochromic anemia (hemoglobin = 10.4 g/dL; MCV = 77.4 fL; MCHC = 26.1 pg), thrombocytopenia (platelet count = 84 G/L), and normal white blood cell count at 4.56 G/L (neutrophils = 3.11 G/L; lymphocytes = 1.2 G/L). The erythrocyte sedimentation rate was elevated at 57 mm/hour. Biochemical parameters objectified hyperferritinemia at 241 ng/mL and a high level of lactate dehydrogenase at 688 U/L.
Peripheral blood smear showed anisopoikilocytosis with mild hypochromia, without platelet clumping. Bone marrow aspiration was normocellular with the absence of megakaryocytes. It was infiltrated by 31% of large histiocytes with hypochromatic nuclei and abundant vacuolated cytoplasm, without emperipolesis (Figure 1). An infiltration by mature histiocytic cells was also observed in bone marrow, lymph nodes, and bone biopsies (Figure 2). Immunohistochemically, the histiocytes were positive for CD68 and S100 protein but negative for CD1a (Figure 3). A diagnosis of RDD involving bone marrow and bones was made. No concurrent malignancy was detected. Lymph node tuberculosis was ruled out because there was no histological evidence. Antinuclear antibodies, anti-DNA antibodies, and rheumatoid factor were absent, which ruled out an associated autoimmune disease. Serological tests for hepatitis B and C, syphilis, and cytomegalovirus were negative.
Neck ultrasound confirmed the presence of bilateral cervical lymphadenopathies. Chest and neck CT scan revealed bilateral lytic bone lesion involving both scapulas and bilateral cervical lymphadenopathies.
The patient has first received analgesics as a symptomatic treatment. On day 6 of admission, the patient's clinical course was deteriorated. She presented signs of septic shock: fever at 40 , hypotension with increased C reactive protein at 47 mg/L. The patient was transferred to the pediatric intensive care unit for appropriate management. Empirical antibiotic therapy was initiated (imipenem + vancomycin). However, the blood culture was negative without any microbiological evidence. The patient died one week after admission to the hospital before the final establishment of RDD diagnosis. | null | Not supported with pagination yet | null |
PMC10003339_02 | Male | 0 | Fifteen days later, his sister was admitted to our hospital for jaundice. The patient was 27 days old, G4P2, and delivered by caesarean section after 40 weeks and 4 days of gestation. Her Apgar score at 5 min and 10min after birth was 9 and 10. her birth weight was normal (4000 g). She was also born with skin hyperpigmentation ( Figures 1C, D ) but never had hypoglycemia.
Jaundice appeared four days after birth. It was initially relieved by phototherapy, but gradually worsened after phototherapy was stopped. Laboratory examination revealed that the cortisol level was low, and extremely high morning ACTH was observed ( Supplementary Table 2 ). She had normal glucose, electrolytes and renin levels ( Supplementary Table 1 ). Thyroid hormone levels were normal, but elevated total bilirubin (Tbil), direct bilirubin (DBIL), indirect bilirubin (IBIL), and total bile acid (TBA) were observed, cardiac ultrasound revealed that she suffered from mild mitral and tricuspid regurgitation, while the electrocardiogram was normal ( Supplementary Table 2 ). Sanger sequencing confirmed that the sister had the same homozygotic variants in c.712C>T/p.H238Y in MC2R ( Figure 1E ). The pedigree of the family is shown in Figure 2 . The sister received oral hydrocortisone at a dose of 10 mg/m2 body surface area. To date, no readily visible side effects have been observed. Informed consent was obtained from the parents for the publication of this case.
This variant was located in the transmembrane domain (PM1) and not reported in the dbSNP152, gnomAD, 1000 Genome Database, or Exome Variant Server (PM2). In-silico tools predicted this variant would be pathogenic (SIFT: Damaging, Mutation taster: Disease causing, Polyphen-2: Probably damaging, CADD: Pathogenic and Revel: Damaging), and it was located at a highly conserved site (PP3), the protein model was constructed and polar contacts of wild-type and mutated amino acid residues were compared ( Supplement Figure 1 ). A previous work showed it to be a causal variant for FGD1[8], and it was observed in the trans position against other MC2R pathogenic variants R145C (PM3). The variant was observed in both affected siblings (PP1). Thus, the variant produced PM1+PM2+PM3+PP1+PP3, which met pathogenic criteria. | acth resistance, chinese siblings, fgd1, mc2r, homozygous mutation | Not supported with pagination yet | null |
PMC4014820_01 | Male | 12 | We report a case of a 12-year-old boy with no significant past medical history who presented at Phoenix Children's Hospital Emergency Room following a motor vehicle accident (MVA). The patient was sharing a seatbelt with one other sibling in the back seat of a 4-door sedan. The vehicle was involved in a "T-bone" collision, which resulted in a temporal head injury against the side door. At the time of presentation, the patient complained of neck tenderness, pain at the right skull base, and nausea. The patient did have poor recollection of the accident; however, there was no indication of loss of consciousness. The patient denied any neck or head pain prior to the accident, and denied any fever, chills, emesis, or seizures. Prior to his presentation, the patient was otherwise healthy, performed well in school, has no family history of coagulopathies, was not taking any medications, and had a negative review of systems except what was discussed earlier. On physical examination, the patient was alert and oriented and appeared well nourished and well hydrated. His pupils were equal and reactive to light, extraocular movements were intact, his smile was symmetric and his hearing present in both ears. He had no otorrhea or rhinorrhea, but some ecchymosis was noted around the right ear. There was some neck tenderness at the level of C3, a neck brace was applied as a precautionary measure pending imaging results. He had full power and normal tone in his upper and lower extremities. His pulses were equal bilaterally to palpation. Overall, the patient was clinically stable but remained somewhat confused with a Glasgow coma scale (GCS) of 14. The patient was admitted to the pediatric intensive care unit pending imaging studies.
A computed tomography (CT) of the head [Figure 1a] on presentation revealed a small petrous bone fracture on the right side of the skull. Several small pneumocephalic collections were evident surrounding the fractured mastoid air cells. Bony fragments were visible within the vicinity of the sigmoid sinus. A magnetic resonance venography (MRV) [Figure 1b] was ordered to evaluate the cranial vascular integrity, which demonstrated a flow void of the right sigmoid sinus and the right external jugular vein.
The patient's coagulation profile was within normal limits, he was admitted and started on IV heparin and monitored with serial exam for changes in neurologic function. The patient remained stable and on the third day of admission, a repeat MRV [Figure 2] demonstrated persistent flow void of the sigmoid sinus, but improved flow through the external jugular sinus. At this point, the patient's nausea and headache had resolved and he was switched to low molecular weight heparin (enoxaparin) and transferred to the pediatric floor. The remainder of the hospitalization was uneventful, the patient was discharged on day 7 with 6 weeks of low-molecular weight heparin (LMWH) therapy with weekly clinical follow up. | anticoagulation, cerebral venous thrombosis, head trauma, pediatric, sigmoid sinus thrombosis, trauma | Not supported with pagination yet | null |
PMC4681976_01 | Female | 35 | A 35-year-old African American woman presented with a three-week history of intermittent low-grade fever, progressive dyspnea, and hemoptysis (approximately 30-40 ml/day). She reported no weight loss or sick contacts. She had two negative TB skin tests in the last two years prior to presentation, as an employee of the corrections department. She had been working in a business office setting for the year prior to the hospital visit. A chest x-ray two years prior to the presentation for pre-operative evaluation for a fibroid surgery was essentially normal. There were mild hilar calcifications which were thought to be associated with old histoplasmosis. (Fig. 1a) Chest x-ray during the current admission revealed bilateral upper lobe opacities (Fig. 1b). Her Human-Immunodeficiency Virus (HIV) test was negative and quantitative immunoglobulin levels were normal. She denied using intravenous drugs. The amount of hemoptysis was concerning and thus she had a flexible bronchoscopy (FB) which identified blood trickling from the left upper lobe into the left main-stem bronchus. Computed tomographic angiography (CTA) was done which showed biapical cavitary lesions with infiltrates and pulmonary artery aneurysms (Fig. 2 a, b and c). Her hemoptysis rapidly worsened, and she was emergently intubated and taken to the interventional radiology where a pulmonary angiogram confirmed three left upper lobe aneurysms, two of which were actively bleeding (Fig. 3a and b demonstrate one of the aneurysms). She underwent emergent glue embolization of all three aneurysms (Fig. 4). She remained stable post-procedure without further hemoptysis. Sputum and bronchoalveolar lavage (BAL) specimens were smear positive for Acid-Fast Bacilli (AFB) and grew Mycobacterium tuberculosis complex that was sensitive to all first line anti tuberculosis drugs. Patient was treated for tuberculosis and has now completed her course of ATT with no further episodes of hemoptysis.
After the diagnosis, the contact investigations by the health department, found 8 more patients with active infection at her office, which was the business office of a dance club. | pulmonary artery aneurysm embolization, pulmonary tuberculosis, rasmussen's aneurysm | Not supported with pagination yet | null |
PMC5629836_01 | Female | 19 | A 19-year-old woman was admitted comatose at the Emergency Department after a fall from a motorbike (reported low speed but no helmet) with severe TBI. She presented with a GCS of 5/15 (by component: Eyes 1, verbal 2, and motor 2) and 3 mm non-reactive pupils bilaterally. The computed tomography (CT) brain scan at admission showed few left frontal and temporal contusions, a small left frontal epidural hematoma and diffuse brain edema [Figure 1] and the decision was for nonsurgical management.
The patient was intubated and admitted to the intensive care unit (ICU) after placement of an intraparenchymal catheter for measuring and managing of intracranial pressure (ICP) [Figure 2]. The patient was treated conservatively and her condition remained stable with ICP readings of 7-17 mmHg for the following 6 days.
On the afternoon of the 7th post-injury day, while in ICU care, the patient presented an increase in ICP (>25 mmHg with surges of >30) and bilateral non-reactive mydriasis (7 mm). Initial decision was for conservative treatment using mannitol, hyperventilation, and barbiturate coma that controlled the ICP in a range of 17-27 mmHg, but despite that, mydriasis was resistant for >12 h. A reassessment of the patient's condition led to a decision for a final attempt at salvaging the patient by performing decompressive craniectomy.
The pupils were checked immediately before the operation, but no recovery was observed. The patient was then operated using a wide decompressive craniectomy that encompassed bilaterally frontal and temporal areas, and extended as far as possible in the parietal bone. No bony bridge was left above the superior sagittal sinus in the area of the craniectomy; undercutting and smoothing was also performed at the edge of the parietal bone. Furthermore, due to excessive swelling of the underlying brain, we decided to perform dural incisions instead of flap durotomy [Figures 3 and 4].
While immediately postoperatively the patient pupils did not change, the patient's condition presented gradual improvement over the period of the next 3 weeks. She was able to be decommitted from mechanical ventilation, be transported back to the neurosurgical ward and commence physiotherapy, and active kinesiotherapy. The patient's tracheostomy was removed and the patient's outcome at 1 month post-injury was at Glasgow Outcome Scale (GOS) 4 (moderate disability), reaching a GCS of 13/15 (by component: eyes 4, verbal 3, and motor 6). A 1-month post-injury magnetic resonance imaging (MRI) scan also showed significant improvement of the intracranial lesions [Figure 5].
The patient's significant improvement was halted by complications in the form of delayed recurring refractory infections (pulmonary and systematic sepsis) and her clinical status gradually deteriorated, leading to her death due to sepsis after 3 months (ultimately GOS 1) despite combined management with the hospital's infections team. | brain edema, decompressive craniectomy, dilated pupils, intracranial hypertension, traumatic brain injury | Not supported with pagination yet | null |
PMC9178119_01 | Male | 61 | A 61-year-old non-smoking Chinese male visited our hospital in August 2017, because of a persistent cough for over one month. He had hypertension for two years, taking lercanidipine tablets for blood pressure control, without any medical history of diabetes, pulmonary tuberculosis, or drug allergy. Positron emission tomography (PET) and computed tomography (CT) examinations revealed the presence of a lesion in the right upper lobe ( Figure 1A ) and multiple lymph nodes metastases at the right hilum of the lung, right mediastinum, the right-side clavicle, and pleural effusion in the right side. The percutaneous biopsy and immunohistochemistry (IHC) analysis revealed a poorly differentiated adenocarcinoma (ADC, Figure 1K ) with positive expression of Napsin A, thyroid transcription factor-1 (TTF-1), and negative CK5/6. The EGFR L858R mutation was detected ( Table 1 ) by the capture-based hybrid next-generation sequencing (NGS, GeneseeqPrime ) targeting 425 cancer-related genes ( Supplementary Table S1 ). He was primarily diagnosed with a stage IV ADC of the right lung (T2N3M1a) and received gefitinib as the first-line treatment. Partial response (PR) was achieved after one month ( Figure 1B ) and progression-free survival (PFS) was 27 months for the first-line gefitinib treatment. During the treatment of gefitinib, the patient experienced grade 2 rash, which was symptomatically treated.
In December 2019, multiple metastatic lesions were found in both lungs and rapidly progressed. As shown in Figures 1C, D , the two CT images taken with an interval of 19 days (2019.12.06 and 2019.12.25) showed over two times size increase on multiple metastatic sites. As the primary tumor remained stable, a re-biopsy of the metastatic lesion was performed. However, the pathological examinations suggested a histology change to squamous cell carcinoma (SCC, Figure 1L ) with positive expression of CK5/6 and P63 but negative for NapsinA and TTF-1. The SCC antigen and CYFRA21-1 levels in serum were significantly increased compared to the baseline tests ( Figure 1J ). He firstly received one cycle of paclitaxel (175 mg/m2), carboplatin (AUC5) plus endostar (15 mg/m2). Then, the IHC test showed a positive PD-L1 expression with a tumor proportion score (TPS) of over 50% ( Figure 1M ). The L858R mutation of EGFR was maintained in the metastatic SCC and companied by the amplification of MET, CD274, and PDCD1LG2 ( Table 1 ). Thus, a combination of paclitaxel (175 mg/m2), carboplatin (AUC5) plus pembrolizumab (200 mg) was administrated. The follow-up examination after one cycle of combined treatment showed that the rapidly progressed metastatic lesions had been under control ( Figure 1E ). Then, partial response was achieved after an additional 5 cycles of this combined therapy and another four cycles of paclitaxel (300 mg) plus pembrolizumab (200 mg) were performed as maintained treatment. The disease remained stable until August 2020 and the patient tolerated well with current treatment.
Due to the progression of the primary tumor in August 2020, a second biopsy for the primary site was performed ( Figure 1F ), whose pathologic histology was still ADC ( Figure 1N ) with dramatic decreases in the levels of SCC antigen and CYFRA21-1 in serum ( Figure 1J ). Compared to the mutational profile of the metastatic SCC lesion, the progressed ADC maintained the oncogenic EGFR (L858R) mutation. However, the amplification of MET, CD274, and PDCD1LG2 was not detected ( Table 1 ). Whereas no genetic alterations were detected in the circulating tumor DNA by targeted NGS which suggested a very low level of tumor mutational burden. After a total of 3600cGy radiotherapy targeting the progressed primary lesion (12 times in 4 weeks), the patient continued pembrolizumab (200 mg) treatment until the March of 2021.
Multiple metastatic sites were found by repeat PET-CT including kidney, liver, and chest wall ( Figure 1G ) with a dramatic increase in carcinoembryonic antigen (CEA) level ( Figure 1J ). The metastatic chest wall lesion was pathologically identified as ADC ( Figure 1O ) with the same genetic alterations as the progressed ADC ( Table 1 ). Due to the clearance of the gene amplification of CD274 and PDCD1LG2, the IHC test of PD-L1 was negative for the chest wall lesion ( Figure 1P ). A combination treatment of pemetrexed (500 mg/m2), carboplatin (AUC5), and bevacizumab (7.5 mg/kg) led to a stable disease for five months until August 2021. With the progression on the metastatic chest wall lesion ( Figure 1H ), afatinib (40 mg/d) and anlotinib (10 mg/d) were administrated to the patient, but anolotinib was discontinued after one month because of severe side effects, including hemoptysis and tooth loss. Afatinib monotherapy relieved chest pain and led to a PR of the metastatic chest wall lesion as shown by the CT scan in December 2021 ( Figure 1I ). Until the last follow-up in January 2022, the PFS upon afatinib treatment reached five months and the treatment is ongoing. | egfr tki, pd-l1, adenocarcinoma, case report, squamous cell carcinoma | Not supported with pagination yet | null |
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