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PMC9528542_02 | Female | 7 | Her history includes treatment for a cold abscess in 2018, following which antitubercular treatment was initiated and completed. She was born of a nonconsanguineous marriage and had no history of similar illness reported in the family. She is married and has a 7-year-old son. She was not on any medication when she presented to our surgery OPD.
Following surgery consultation in our hospital, she underwent ultrasonography and fine-needle aspiration cytology. The findings were consistent with branchial cyst. Preanesthetic workup picked up a saturation gap (SPO2 was 84% in room air with ABG showing PO2 of 98.5 mmHg) for which a hematology consultation was done.
A detailed evaluation was done at the hematology department which revealed a history of dark brown-colored blood on cuts in the past. A history of giddiness and easy fatigability was present. On examination, she had cyanosis in oral cavity and tongue. There is no history of exposure to any chemicals, antimalarial, fava beans, drug allergy. Considering all the positive finding including saturation gap, a decision was taken to evaluate for methemoglobinemia.
A complete workup including a complete blood count, reticulocyte count, peripheral blood smear, liver function test, renal function tests was done. Cardiology and pulmonology evaluation to rule out secondary causes of cyanosis was also done. Special tests to investigate for methemoglobinemia were also advised done. Her blood investigation is as shown in Table 1.
Genetic analysis revealed a novel mutation (R192C) in CYBR3 gene which is associated with an autosomal recessive congenital methemoglobinemia type 1. NADH-cytochrome b5 reductase (cytb5r) enzyme activities were measured by standard methods, and molecular analysis was performed by polymerase chain reaction followed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software and PyMOL molecular graphics program. Spectroscopic analysis of the hemolysate showed normal peaks suggesting the absence of Hb-M. Molecular characterization showed a novel homozygous mutation p. Arg192Cys in CYB5R3 gene is an evolutionarily conserved position located in exon 7. This mutation has been elucidated as a possibility of high prevalence of heterozygous in Indian population causing type I restrictive cardiomyopathy. The patient was started on Vitamin C and niacin. Samples were sent for G6PD levels before initiating methylene blue for surgery. Unfortunately, her G6PD levels came back as deficient: 5.9 units/g of Hb (6.97-20.5). She was advised to continue Vitamin C and niacin and to review after 1 month. It was also decided to do a G6PD genetic workup too for the patient.
Her G6PD genetic study was suggestive of G6PD Kerala Kalyan pathogenic heterozygous variant. In India, around 13 variants have been characterized biochemically and as per the mutation studies, the most common variants are G6PD Mediterranean (563 C-->T; 60.4%) followed by G6PD Kerala Kalyan (949 G-->A; 24.5%) and G6PD Orissa (131 C-->G; 13.3%). G6PD Chatham (1003 G-->A) with undetected red cell enzyme activity and G6PD Insuli (989 G-->A) with normal G6PD activity were very rare in the Indian population.
G6PD Kalyan, a mildly deficient variant first described in the Koli, a tribal group inhabiting the Kalyan district of Bombay. G6PD Kerala reported in Indians living in the Pacific North West of America, originating from Kerala state. Both were independently identified and later clubbed together to become Kerala Kalyan pathogenic heterozygous variant G6PD. A single base change was found, namely a G:A transition at nucleotide position 949 in exon 9, resulting in the substitution of lysine for glutamic acid at amino acid position 317. Being a mild variant, she was taken up for surgery with adequate precautions. She reviewed after 1 month with a preoperative saturation of 90% in room air. After detailed discussion with anesthesia department, a patient-specific protocol was formulated to ensure safe surgery. Our plan was to avoid methylene blue and dehydration along with monitoring for acidosis, hypoxia, sensorium, and renal function. Plan for hyperbaric oxygen therapy and exchange transfusion if the need arises was also discussed. Propofol and atracurium were used for induction and muscle relaxation, respectively. Maintenance of anesthesia was achieved using oxygen, air, and sevoflurane. Throughout the surgery, her saturation was maintained at 93%. The surgery and postoperative period were uneventful. She was discharged on postoperative day 4. It was also decided to the send the blood samples of family members for Methemoglobinemia and G6PD genetic screening as it is a rare phenomenon. | glucose-6-phosphate dehydrogenase, methemoglobinemia, novel mutation | Not supported with pagination yet | null |
PMC5788106_01 | Unknown | 1 | After approval by our institutional review board (No. 08-001342), all patients with a history of primary MPFL reconstruction at our institution from 2005 to 2013 were identified in a surgical database with Current Procedural Terminology and International Classification of Diseases codes. Patients were included if they (1) underwent primary MPFL reconstruction at our institution for recurrent patellar instability after failed nonoperative treatment, (2) had pre- and postoperative lateral knee radiographs within 1 year of surgery, and (3) were >=18 years old at surgery. Patients were excluded if they had (1) concomitant cruciate ligament reconstruction, (2) multiligament knee injury, (3) no lateral knee radiographs, (4) tibial tubercle-trochlear groove (TT-TG) measurement >20 mm, and (5) moderate trochlear dysplasia (Dejour type C or greater) and were (6) <18 years old at the time of surgery. A total of 32 patients satisfied these criteria and were included in the study.
Chart review was performed to verify patient information (age, sex, surgical characteristics) and pre- and postoperative lateral knee radiographs. All lateral radiographs were performed with the knee positioned in 20 to 30 of flexion and the epicondyles perpendicular to the image receptor. Lateral radiographs were assessed for patellar height with the Caton-Deschamps, Blackburne-Peel, and Insall-Salvati ratios. Two authors (J.M.W. and R.A.C.:an orthopedic sports fellow and a chief resident, respectively) calculated these ratios to ensure interrater reliability (Figure 1). Means of the measures between the 2 observers were calculated and used to compare pre- and postoperative patellar height. Mean values of patellar height in the cohort were compared with values reported in the literature as normal. Femoral tunnel location was plotted in relation to Schottle's point on a true lateral femoral radiograph. A position within 7 mm of this point was considered anatomic as described by Servien et al.
Isolated MPFL reconstruction was performed at a single institution by 1 of 3 senior authors (A.J.K., D.L.D., M.J.S.) on patients with a clinical history of RPFI and a positive apprehension test result. Diagnostic arthroscopy was performed in all cases, with grading of the cartilage status of both the undersurface of the patella and the femoral trochlea. Mechanical chondroplasty of unstable cartilage was performed when indicated.
After diagnostic arthroscopy, the graft (11 semitendinosus autografts, 2 quadriceps tendon autografts, 11 gracilis autografts, and 8 gracilis allografts) was prepared with a running whipstitch placed in both free ends. A 4-cm incision was made over the medial aspect of the patella. Sharp dissection was carried down to the medial retinacular layer, where the interval between medial layer 2 (retinaculum) and medial layer 3 (capsule) was then defined for graft passage. A small shallow trough was then created in the superomedial aspect of the patella, in the area of the native MPFL origin. The graft was then secured to the patella with two 2.8-mm FASTak suture anchors (Arthrex) or two 3.5-mm biocomposite SwiveLock anchors (Arthrex), spaced 1 cm apart. The femoral insertion point was identified by fluoroscopy, according to the method described by Schottle et al. An incision was made at this designated point, and sharp dissection was performed down to the medial aspect of the distal medial femoral condyle. The graft was then looped to create a double-bundle construct, and the free ends were passed from the patella to the femur. The graft was placed around the femoral guide wire as the knee was brought through an arc of motion to test for relative graft isometry from 0 to 90 . The diameter of the doubled graft determined the diameter of the tunnel that was drilled; typically, a 6-mm socket was made by advancing a cannulated drill over the guide wire to a depth of 30 mm. With the knee held in 30 of flexion, a 6 x 23-mm bioabsorbable interference screw (Arthrex) was then used to secure the 6-mm graft in the femoral socket. A layered closure was then performed, sterile dressings applied, and a knee immobilizer initially provided.
Postoperative rehabilitation consisted of a knee immobilizer for 2 weeks and partial weightbearing with crutches for 6 weeks. Range-of-motion exercises were performed immediately and without restriction. Full weightbearing, full knee range of motion, and progressive strength and proprioceptive training were allowed after 6 weeks.
The interclass correlation coefficient was used to quantify interrater reliability for each measure of patellar height. Adequate correlation was accepted as an interclass correlation coefficient >0.5; good, >0.7; and excellent, >0.8. Paired Student t tests were used to evaluate for postoperative changes in each continuous measure of patellar height. The McNemar test for paired categorical data was used to compare the number of patients with patella alta pre- versus postoperatively. All statistical analyses were performed with SAS Statistical Discovery JMP (v 7.0; SAS Inc). Differences in the means of the groups preoperatively and at final follow-up were evaluated, and significance was determined with an alpha level of 0.05. | mpfl reconstruction, patellar height, patellar instability, patellofemoral arthritis | Not supported with pagination yet | null |
PMC3929933_01 | Male | 72 | A 72 years old normotensive, non-diabetic male smoker presented with dull aching pain in the upper anterior chest wall adjacent to sternum, along with cough with scanty, white, mucoid expectoration for one month. His night sleep was disturbed due to severe chest pain which was not relieved by non-narcotic analgesic. He also complained of a gradually progressive hoarseness of voice for fifteen days. He had a history of anorexia and a significant weight loss, but there was no history of hemoptysis or dyspnoea. No past history of pulmonary tuberculosis was present either.
On general survey, he had pallor, clubbing, and left sided supraclavicular lymphadenopathy. His axillary temperature, respiratory rate, pulse rate and blood pressure were 36 C, 16 breaths/minute, 100 beats/minute and 110/80 mmHg respectively. On examination of respiratory process, the chest was acutely tendered in the left infraclavicular area and in sternal region, but no mass was palpable. Percussion note over left second and third intercostal spaces near parasternal area and over sternum was dull. Complete hemogram, blood biochemistry and urinalysis proved normal. Sputum smear for acid fast bacilli and malignant cells was negative. Chest X-ray (posteroanterior view) showed left sided para-hilar mass with irregular margin. Contrast enhanced computed tomography (CECT) of the thorax showed a soft tissue mass in the left upper lobe with variegated appearance and irregular margin without any calcification, associated with left sided mediastinal lymphadenopathy and osteolytic erosion of left half of the manubrium sterni (Figure 1). Radioisotope bone scan using Technetium -99m (99mTc) labeled methylene diphosphonate (MDP) showed sternal deposit without the involvement of other bones. Ultrasound of abdomen was also normal. Fibreoptic bronchoscopy (FOB) showed no endobronchial lesion and bronchoalveolar (BAL) lavage fluid revealed no acid fast bacillus or malignant cell. Fine needle aspiration cytology (FNAC) of left supraclavicular lymphadenopathy showed metastatic squamous cell carcinoma. CT-guided FNAC of the left lung mass showed dispersed clusters of malignant epithelial cells with squamous differentiation and cytoplasmic keratinization in the background of inflammatory cells (Figure 2). CT-guided FNAC of sternal lesion yielded a similar cytology. Hence, final diagnosis was squamous cell carcinoma of left lung with sternum and mediastinal plus cervical lymph node metastases. The patient was advised for cytotoxic chemotherapy comprising of cisplatin and etoposide, but unfortunately, he succumbed to his illness before initiation of first cycle of chemotherapy. | local spread, lung cancer, sternal erosion | CECT thorax showing left upper lobe mass with erosion of manubrium sterni. |
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PMC2808565_01 | Female | 9 | A 9 yr-old girl was admitted to Samsung Medical Center due to chronic productive cough and shortness of breath. During the infancy she developed cough and sputum, which was associated with frequent respiratory tract infection. Diarrhea persisted from 1 month of age regardless of the dietary formula and is unresponsive to antibiotics. Diarrhea led to poor weight gain and generalized edema, which necessitates hospitalization twice. Mantoux test performed at 10 months of her age because of chronic cough was positive (15x15 mm). Hence she was treated with anti-tuberculosis regimen for 9 months, but her symptoms did not improve. When she was 2 yr old, clubbing fingers were noticed, and at 5 yr of age, she received ventilator care due to severe respiratory distress. At that time, Pseudomonas aeruginosa was isolated from her sputum. Since then, her respiratory symptoms were waxed and waned, and she had been hospitalized several times. | null | Not supported with pagination yet | null |
PMC5645167_01 | Male | 46 | A 46-year-old Saudi male right-handed teacher was in his usual state of health until four months prior to his presentation. This was when he started to have a wide-based gait, unsteadiness as well as several attacks of staring and unresponsiveness. It was associated with lip smacking lasting a few seconds as noticed by his colleagues and students at school. The patient would occasionally complain of a holocranial headache lasting hours to days, incapacitating him from doing his duties of teaching and home commitments.
One week prior to his presentation to our institute, he started complaining of severe headache while in class. His colleagues directed him to a local hospital. On his way he developed abnormal movements with loss of consciousness in the car. The semiology of the abnormal movements reflected left-sided tonic-clonic seizures with uprolling of the eyes, urinary incontinence, frothing of saliva that lasted few minutes and was aborted spontaneously. This was followed by a state of confusion for hours.
During the admission at the local hospital, his brother witnessed some tonic posturing of the left arm for an estimated duration of 2 minutes during which the patient was unresponsive to verbal stimuli. The patient was discharged from the local hospital without anti-seizure therapy.
The patient was referred from the local hospital to our center for seizure evaluation. He presented to the Epilepsy clinic at KFSH&RC with altered consciousness and found to have aphasia. He was non-fluent, and following commands by gesture only. He was rushed to the neurophysiology clinic for an urgent electroencephalogram (EEG).
A 30-minute EEG recording revealed non-convulsive status epilepticus (NCSE). It showed a severely abnormal EEG consisting of a slow background of 6-7 Hertz (Hz) with 1-3 Hz focal slowing in the left anterior and mid temporal region. Several seizures during the recording were associated with evolution of sharp waves and spikes recurring at 3-5 Hz over the left mid and posterior temporal region. During this time the patient was unresponsive with eye blinking. This expedited his admission for investigation and management of his seizures.
He was admitted with a diagnosis of NCSE, started on intravenous (IV) phenytoin and long-term EEG monitoring. He continued to have frequent attacks of non-convulsive seizures, despite being on multiple anti-seizure drugs including lamotrigine, carbamezapine, valporic acid and pyridoxine. Long term EEG monitoring captured 13 attacks of seizures during the first 48 h. Electrographic seizure onset occurred with the onset of rhythmic sharply-contoured theta evolving to delta activity maximal in the left temporal region during unresponsiveness for 5-7 minutes.
Computed tomography (CT) brain was unremarkable for any abnormality. Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis showed an elevated protein of 747 mg/dl, and white blood cells (WBC) of 51 with 94% lymphocytes. Because the CSF analysis revealed lymphocytic pleocytosis in the presence of NCSE, the patient was started on antiviral and antibiotics for possible meningo-encephalitis. CSF viral and bacterial etiologies as well as, mycobacterium tuberculosis, syphilis, brucella and sarcoidosis were ruled out.
Brain Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography and Magnetic Resonance Venography was performed. Brain MRI revealed the presence of multi-territorial, scattered small deep white matter lesions on the fluid-attenuated inversion recovery (FLAIR) sequence involving the right corona radiate, right inferior cerebellar and cortical areas of the left parietal lobe with corresponding slight enhancement following gadolinium administration. There was no major arterial vascular occlusion, and preserved flow related enhancement of the major dural venous sinuses. The images were thought to be radiologically suggestive of inflammatory vasculitic lesions or ictal hypoxemia. (Fig. 1).
The seizures became drug-resistant despite extensive investigations and maximum therapy for 48 h with antibiotics, antiviral and the multiple anti-seizure medications. At that point, the diagnosis of NORSE was entertained.
Autoimmune encephalitis was suspected. Serum and CSF autoimmune and paraneoplastic markers were obtained and the patient was started empirically on intravenous steroids for three days. Erythrocyte sedimentation rate (ESR) was mildly elevated. Surprisingly, the patient's autoimmune workup including C-reactive protein, antinuclear antibodies, rheumatoid factor (RF), cytoplasmic anti-neutrophil cytoplasmic antibody titers and cryoglobulins were negative (Table 1, Table 2). A CT scan of the chest, abdomen and pelvis was done and revealed no abnormalities. Cerebral angiogram was done as part of the workup for CNS vasculitis and showed no evidence of small vessel disease. (Fig. 2) Despite extensive investigation no identifiable cause could be delineated.
Interestingly, his speech, gait and orientation improved dramatically returning to near normal after the intravenous pulse steroid therapy. He was discharged on oral prednisolone tapering dose, and scheduled for follow up Brain MRI 3 months from the discharge date.
On follow up, he was doing well clinically with great satisfaction in performing the daily activities independently, but still unable to return to work. His repeated brain MRI showed dramatic worsening which was attributed most probably to the tapering of corticosteroid (Fig. 3). He was readmitted for further investigation for investigation of the worsening Brain MRI. LP was repeated and showed elevated protein of 454 mg/dl and WBC of 2 cells.
Inclined to reach a diagnosis, brain biopsy was performed and the histopathology picture was suggestive of small vessel vasculitis. The biopsy was composed of many cortical and white matter fragments showing many focal angiocentric mononuclear inflammatory cell infiltrates composed almost exclusively of lymphocytes, predominantly T cells (Fig. 4). Patient was started on cyclophosphamide and showed a dramatic response to the treatment. | cns angiitis, cns vasculitis, norse, primary angiitis, status epilepticus | Not supported with pagination yet | null |
PMC9872259_01 | Female | 38 | 38 years old Malay lady presented with a month's history of bilateral neck swelling. The swelling was painless, gradually increasing in size and did not reduce any neck movement. She also experienced intermittent fever but was not associated with any other constitutional symptoms such as chills, weight loss, anorexia and night sweats. There was no history of epistaxis, rhinorrhea, nasal blockage, chronic cough, sore throat, hoarseness, ear fullness, tinnitus, or hearing impairment.
She sought treatment at the health clinic and was prescribed with a course of oral augmentin. However, the neck swelling persisted. She had no history of contact with pulmonary tuberculosis-infected individuals and no history of malignancy in her family.
Neck examination revealed two lymph nodes over the left posterior triangle at level 5a, each measuring 1.5cm x 1.5cm and 3cm x 3cm, firm in consistency and non-tender.
On the right side of the neck, there was one lymph node at level 2 measuring 3cm x 3cm with similar characteristics. Oropharynx and ear examinations were unremarkable. Nasoendoscopy examination revealed a centrally located mass predominantly at the left posterior nasopharyngeal wall with an irregular surface but an otherwise normal fossa of Rosenmuller (FOR) and Eustachian tube (Figure 1).
Blood parameters were within normal limits with the erythrocyte sedimentation rate (ESR) value of 14 mm/hour and a negative sputum acid-fast bacilli (AFB) staining. Chest radiography showed normal lung findings.
Fine needle aspiration (FNAC) was performed over the left posterior triangle lymph node and showed features consistent with the necrotic lymph node. However, tuberculous lymphadenitis or tumour necrosis cannot be excluded from the cytological findings. Therefore, a contrasted enhanced computed tomography (CECT) scan was done and revealed a well-defined enhancing hypodense lesion, predominantly at the left posterior nasopharyngeal wall, measuring 8.2mm x 6.2mm, without any extension towards bilateral FOR (Figure 2a, 2b).
There were also enlarged rim-enhancing hypodense lesions over bilateral level 2 and left level 5a of the neck (Figure 2c).
An excision biopsy of the left posterior triangle lymph node and a biopsy of the nasopharyngeal mass was performed under general anaesthesia. Histopathological examination (HPE) revealed epithelioid cell granulomas with central areas of necrosis surrounded by epithelioid cells mixed with lymphoplasmacytic cell infiltrates and occasional Langhans type multinucleated giant cells (Figure 3).
No fungal elements, atypical or malignancy cells present. Surprisingly, the Ziehl-Neelsen (ZN) stain for acid-fast bacilli was negative. A further study performed on the paraffin-embedded tissue for mycobacterium (MTB) polymerase chain reaction (PCR) was also negative for acid-fast bacilli. Given the histopathological findings showing typical features of necrotizing granulomatous lymphadenitis together with the clinical presentation, a diagnosis of nasopharyngeal tuberculosis was made. She was referred to the chest clinic at Hospital Sultan Abdul Halim, Sungai Petani, for the commencement of directly observed treatment short-course (DOTS) for nasopharyngeal tuberculosis.
She was treated with an anti-tuberculous therapy regime consisting of Isoniazid, Rifampicin, Ethambutol, Pyrazinamide and Pyridoxine for 2 months during the intensive phase followed by 4 months of Isoniazid and Rifampicin during the maintenance phase. Upon completion of her intensive phase of treatment, her neck swelling had completely resolved, and the nasopharyngeal mass was no longer visualized. | lymphadenopathy, nasopharyngeal mass, neck mass, tuberculosis | Not supported with pagination yet | null |
PMC6349988_01 | Female | 6 | A 6-year-old female with a history of left FH and limb-length discrepancy presented for orthopedic evaluation of knee instability. Anterior tibial instability appeared to be the most pressing clinical issue with frequent subluxation episodes. The patient's medical history revealed a left Achilles tendon lengthening at 11 months of age. Bilateral imaging of the legs revealed an absent left fibula (Figure 1). The patient's left leg was 3.5 to 4 in. shorter than the right with the left foot also smaller in size than the unaffected right side. On the affected left side, she was also ACL and PCL deficient. Physical exam revealed a normal straight leg raise with full range of motion, a grossly positive Lachman at 30 of knee flexion and a positive tibial sag at 90 of knee flexion. Varus-valgus stress tests in full extension and in 30 of flexion were normal.
Previous consultations with a pediatric orthopedic surgeon addressed procedures to potentially equalize the length of the legs through limb lengthening. Specifically, a tibial osteotomy of the left leg with the application of ring external fixator was recommended. It was also recommended that prior to the lengthening surgery, the knee ligaments should be stabilized. The patient was primarily symptomatic with instability from the anterior; this was visibly evident with anterior tibial subluxation episodes during walking. She was thought to be a candidate for ACL reconstruction using the Micheli procedure, a physeal-sparing technique utilizing the patient's iliotibial band (ITB) autograft. However, due to the degree of anterior laxity and the expected small width and thickness of the ITB, graft augmentation procedures were considered.
In the operating room, the exam under general anesthesia again revealed a grossly positive Lachman with an excess of 2 cm of anterior tibial translation and a positive pivot shift. Her medial collateral ligament and laterlal collateral ligament were intact and stable and the PCL absent. A photo of the legs demonstrates the marked difference in limb length (Figure 2).
After incision and exposure of the lateral thigh, a portion of the ITB was harvested producing a graft, 120 mm in length and 10 mm wide (Figure 3(a)). As the graft was considerably small in cross-section, and the anterior tibial laxity was quite significant, the decision to use a semitendinosus allograft to augment the reconstruction was made (Figure 3(b)). The allograft was baseball stitched to the ITB under tension.
Arthroscopic examination of the knee was consistent with the clinical examination finding of complete absence of both the cruciate ligaments (Figure 4(b)). In addition, she had a relatively small notch. The geometry of the notch was not altered at the time of surgery because of the relatively horizontal position of the ACL graft, nor was the posterior cruciate ligament deficiency addressed. The femoral portion of the graft was sutured to the intermuscular septum, while the tibial side was sutured to the periosteum of the proximal anterior tibia at 0 of extension after being passed intra-articularly. This patient was very young and therefore had a small transverse meniscal ligament. After intra-articular routing of the graft, it was decided to not place the graft under the intermeniscal ligament as is normally done in the Micheli procedure as a precaution to avoid damage to intermeniscal ligament. After the graft was secured to the tibia with sutures in the periosteum (Figure 4(a)), the Lachman exam was repeated and the anterior laxity of the tibia on the femur had been minimized. Anterior tibial translation was reduced to an appropriate 3 mm at 30 of flexion. The patient tolerated the procedure well and left the operating with the leg in full extension in a posterior splint. The patient returned to the clinic 13 months postoperatively. She subjectively reported that she has been very active playing on the playground with friends and feels that the knee is quite stable and strong. Her physical exam revealed full range of motion from 0 to 140 with no terminal flexion pain, a stable Lachman's exam, good quadriceps contraction from a straight leg raise, and no tenderness to palpation along the ITB. Radiographic imaging of the knee and tibia revealed no growth alterations or damage to the physes on the proximal tibia or distal femur. | sports medicine, orthopedics/rehabilitation/occupational therapy | Not supported with pagination yet | null |
PMC4774465_01 | Female | 73 | A 73-year-old female with a past medical history of hystero-oophorectomy for uterine cancer at 60 years of age, who had never smoked, was examined in our department (Respiratory Medicine and Infection Control, Tokai University Hachioji Hospital, Tokyo, Japan) on November 12, 2012 after abnormal chest shadows were observed during a health check-up with a radiographer. The patient had no fever or cough, and no particular clinical manifestations were observed. Additionally, no superficial lymph nodes were palpable, and no skin rashes were noted. Chest radiography and computed tomography (CT) revealed infiltrative shadows primarily in the left pulmonary hilum, and small nodular shadows in both the right and left lung fields (Figs. 1 and 2). The blood examination and tumor marker results were within normal limits (CEA 2.0 ng/mL, CYFRA 1.1 ng/mL, RProGRP 31.6 pg/mL, NSE 8.7 ng/mL, sIL-2R 327 U/mL and KL-6 410 IU/mL); the interferon-gamma release assay for active tuberculosis (IGRA: T-SPOT.TB) was negative, and neither sputum cultures or cytology yielded any significant findings. Two weeks following the first relevant examination (FRE), a transbronchial lung biopsy (TBLB) was performed on the patient on November 26, 2012, who was admitted to the Tokai University Hachioji Hospital overnight. Histopathological assessment of the biopsy tissue revealed nonspecific organized tissue with no evidence of malignancy. No clinical manifestations were observed during that time; however, a definitive diagnosis was deemed necessary, and after consulting with the patient and obtaining consent, video-assisted thoracic surgery (VATS) and excision of the right upper nodule was performed on December 18, 2012, three weeks after the TBLB, for which the patient was admitted until December 28, 2012. Histological evaluation of the frozen material demonstrated the presence of an organizing pneumonia with no malignancy. A detailed pathological evaluation of fixed tissue led to the preliminary diagnosis of an IgG4-related, solitary, fibrous IMT, which required further immunohistochemical investigation. The immunostaining revealed that the nodule was vimentin-positive, strongly alpha-SMA-positive, CD34-negative, CD68-positive, Congo-red-negative, ALK-negative and IgG4-negative (Fig. 3). No evidence of malignancy, including evidence of cancer or spindle-cell carcinoma, was detected. The macroscopic findings showed a clearly demarcated mass. Based on the above findings, a final diagnosis of IMT was made. As there were no clinical manifestations, we consulted with the patient and decided to carefully follow her course. The chronic inflammation in the ALK-negative tissue was considered to be a chronic respiratory tract inflammation at that time. Clarithromycin was administered as a long-term macrolide antibiotic therapy, three months following the FRE, as we expected it would be effective in controlling the inflammation. The chest shadows slowly resolved on follow-up imaging examinations, performed every two months. The chest shadows had almost completely disappeared on the images obtained eight months following clarithromycin therapy (Figs. 1 and 2). Clarithromycin therapy was performed for ten months in total, and during this time there were no clinical manifestations and no impairments to the patient's everyday life. The patient has experienced no relapses, and appears to have followed a favorable course almost one year following the FRE. | anaplastic lymphoma kinase, anti-inflammatory agent, clarithromycin, inflammatory myofibroblastic tumor, macrolide | Not supported with pagination yet | null |
PMC7654211_01 | Female | 50 | On December 2017, a 50-year-old Caucasian woman, previously in good health, developed cutaneous erythematosus papular lesions both on the palmar and dorsal surface of hands and fissuring of the distal fingers, in the absence of other symptoms. She consulted a dermatologist who prescribed topical steroids. Three months later, Raynaud's phenomenon and dryness of the skin appeared. She consulted a rheumatologist who, after laboratory examinations showing antinuclear antibody (ANA) positivity, made the diagnosis of undifferentiated connective tissue disease (UCTD) and prescribed prednisone 25 mg daily with progressive tapering until 12.5 mg daily, with partial improvement. Two months later, she developed arthritis of hands and wrists, alopecia, and worsening of the skin lesions. She consulted another rheumatologist who added hydroxychloroquine 400 mg daily without any improvement. Instead, asthenia, muscle weakness, and pain appeared. For this reason, the rheumatologist prescribed cyclosporine 160 mg daily; hydroxychloroquine was stopped because of the onset of vertigo, which disappeared with drug suspension, while prednisone 12.5 mg daily was continued. On October 2018, because of further worsening of asthenia and myalgia and the onset of mild dyspnea, high-resolution computed tomography (HRCT) of the chest was performed, and it showed initial signs of ILD.
Then, the patient was referred to our attention and she was admitted to our rheumatology ward.
Concerning the medical history, she did not report comorbidities, pregnancies, or miscarriages. She had smoked for ten years, but she was not smoking anymore. She was in menopause from the age of 45. Her family history was unremarkable. At the physical examination, she was afebrile, normotensive, and breathing and cardiac rates were, respectively, 16 times/min and 90 beats/min. Cardiac and abdominal examinations were normal; pulmonary examination showed fine bilateral basal crackles. There were papular erythematosus lesions on both the palmar and dorsal surface of her hands and extensor surface of elbows and concomitant fissuring of the distal fingers (Figure 1). Musculoskeletal examination did not evidence joint tenderness/swelling or deformity, but it revealed a reduction of muscle strength at the four limbs. Laboratory tests showed a mild normochromic, normocytic anemia, a slight increase of aspartate aminotransferase (AST) (52 U/L; normal range <40 U/L) and of lactate dehydrogenase (LDH) (688 U/L; normal range <400 U/L), a modest polyclonal hypergammaglobulinemia, and an increase of C reactive protein (CRP) (10 mg/L; normal range <5 mg/L), while white blood count, platelets, creatinine, electrolytes, erythrocyte sedimentation rate (ESR), uric acid, alanine aminotransferase (ALT), creatine phosphokinase, and urinalysis were normal. Screening for hepatitis B and C virus was negative, while the QuantiFERON-TB Gold test was indeterminate.
A skin right hand biopsy revealed the presence of interface dermatitis, with perivascular inflammatory infiltrate prevalently at the dermoepidermal junction and injury of the basal cells keratinocytes, as it can be observed either in systemic lupus erythematosus (SLE) or in DM.
Electromyography (EMG) of the upper limbs evidenced signs of median neuropathy in the right hand and no other pathological sign.
Muscle magnetic resonance (MRI) of the lower limbs showed diffuse and symmetric oedema of all the muscles of the thigh without fatty degeneration (Figure 2).
Chest HRCT confirmed the presence of bilateral apical pleural thickening and various subpleural, paramediastinal, and basal areas of reticular thickening associated with ground glass lesions. There was no pleural effusion or linfoadenopathy. Spirometry with diffusing capacity for carbon monoxide (DLco) evidenced signs of a disventilatory obstructive syndrome with severe DLco reduction (53% of the predicted value). Echocardiogram was normal.
A nailfold capillaroscopy revealed different alterations such as a disordered loops architecture, capillary enlargement with some megacapillaries, microhaemorrhages, and neoangiogenesis, suggestive of a "scleroderma-like pattern" (Figure 3).
Indirect immunofluorescence (IIF) for ANA showed a cytoplasmic pattern at a titer of 1 : 160; rheumatoid factor, anti-SSA (Ro), anti-SSB (La), anti-Sm, anti-RNP, anti-Jo1, anti-SCL-70, anti-ds DNA, C3, C4, and anti-citrullinated peptide antibody (ACPA) were normal, while a myositis panel immunoblotting test evidenced anti-MDA5 positivity (53 AU; normal range <10).
Therefore, the patient was discharged with a diagnosis of anti-MDA5 DM and ILD. Prescribed therapy was mycophenolate mofetil 2 gm daily and prednisone 25 mg daily associated with a weekly bisphosphonate tablet and a prophylactic therapy for Mycobacterium tuberculosis.
At the follow-up visit, two months later, the patient reported worsening of fatigue, weakness, and dyspnea. Her laboratory exams showed an increase of inflammatory indexes (ESR 50; normal range <30; CRP 15 mg/L; normal range <5 mg/L), while a spirometry evidenced a further DLco reduction (42% of the predicted value).
After consultation with the respiratory physician, we decided to discontinue mycophenolate and start a second-line therapy with RTX 1000 mg on two occasions 2 weeks apart. Prednisone was continued with progressive tapering to 12.5 mg daily.
Patient was re-evaluated two months later. She reported a marked improvement of fatigue, muscle weakness, and dyspnea. At physical examination, the skin lesions had improved. Laboratory tests showed a reduction of ESR and CRP values (ESR 30; normal range <30; CRP 5; normal range <5 mg/L). DLco parameters were significantly ameliorated (from 42% to 56% of the predicted value). Therefore, it was possible to reduce prednisone dosage from 12.5 mg to 10 mg daily.
The patient is currently under follow-up in our unit. | null | Not supported with pagination yet | null |
PMC10328179_01 | Female | 46 | A 46-year-old female patient with a P2L2 medical history visited our emergency department due to gradual onset of abdominal pain, which was progressively worsening with time. It was more on the right lower quadrant. Movement and touch exacerbated the pain, while rest provided relief. In addition, the patient had experienced symmetrical abdominal distension for over a month, which was accompanied by early feelings of fullness, nausea, diarrhea, and alternating constipation. No incidents of vomiting, heartburn, yellow discoloration, or swelling in the lower limbs were reported. The patient also reported no respiratory symptoms, such as difficulty breathing or coughing. She denied history of contact TB. Vital signs were measured as follows: temperature of 36.7 C, blood pressure of 116/76 mmHg, pulse rate of 90 beats per minute, respiratory rate of 18 breaths per minute, and oxygen saturation of 99% on room air.
On physical examination, the abdomen was distended with normal contour and a small scar in the lower quadrant; normal bowel sounds were heard upon auscultation. Tenderness was noted in the right iliac fossa region, but there were no palpable masses. Both external and internal genitalia were normal upon examination, with a healthy cervix observed. Other systems were unremarkable. The laboratory results showed leukocytosis with a count of 14.5 (4-11) and a predominant 76% of neutrophils, as well as a low hemoglobin level of 10.6 (11.5-16.5). The CA-125 level was elevated to 52.5 (normal range: 0-35 units per mL). The renal and liver function tests, including urea and creatinine levels, were normal. Inflammatory marker C-reactive protein test was high 800 (0.8-3 mg/L). A chest X-ray showed normal results, while the abdominal ultrasound revealed the presence of massive ascites, a suspicious heterogeneous mass in the posterior aspect of the uterus, and mesenteric lymphadenopathies. The findings led to the impression of an ovarian mass and a clinical diagnosis of ovarian cancer. However, due to financial constraints, a computed tomography (CT) scan was not conducted, and no biopsy was performed prior to surgery.
Intra-operatively, no obvious ovarian tumor was encountered instead; disseminated creamy white patches on the uterus and left adnexa were seen. About 4500-mL straw-colored ascitic fluid and disseminated creamy white patches on the bowels and omentum were evident giving an impression of carcinomatosis. Therefore, diagnosis of ovarian cancer was entertained. The liver and right ovary were essentially unremarkable. Total hysterectomy and partial omentectomy were done, and the specimens were submitted for histopathology analysis. Peritoneal fluid was submitted for cytological analysis and for GeneXpert for the TB. While the GeneXpert results were negative, the histopathological studies of the ovary, endometrium, and fallopian tube revealed numerous caseating granulomatous inflammation with Langhans-type multinucleated giant cells (Figure 1). Similar findings were observed on the omental tissue. Ziehl-Neelsen staining confirmed the presence of acid-fast bacilli (AFB) (Figure 2). Therefore, the final diagnosis of FG-TB was established. The patient was kept on anti-TB rifampicin/isoniazid/pyrizinaamide/efavirenz as well as ceftriaxone and antipain medications. She did well immediately after surgery and was discharged on day 5. The patient completely recovered during the 6 months of close follow-up visits and had resumed her daily activities. | female genital tuberculosis, diagnostic challenge, fallopian tube, malignancy, ovary | Not supported with pagination yet | null |
PMC10294283_01 | Female | 28 | A 28-year-old female was referred with progressive left visual loss to no perception of light. She had a background history of smoking, alcohol excess, treated pulmonary tuberculosis, traumatic joint dislocations, hypertension, and dilated cardiomyopathy. The patient was of Pacific Islander ethnicity. There was no clear family history of aneurysm, organ rupture, or joint hypermobility.
The patient first presented to another ophthalmologist with left retrobulbar headache and proptosis, with normal optic nerve function at the time. Magnetic resonance imaging (MRI) scan of the orbits demonstrated a tubular tortuous intraconal enhancing lesion in the left orbit. A conservative approach was adopted, but the patient failed to attend her subsequent follow-up appointments. Four months later, she presented to her local emergency department with at least a 2-week history of severe progressive left visual loss. Computed tomography (CT) venogram at this point reported a single left orbital vascular lesion with no evidence of thrombosis. She was then referred urgently for a formal ophthalmic assessment.
On examination, her visual acuity was no perception of light in the left eye and 6/5 in the right. Intraocular pressures were normal. There was a left relative afferent pupillary defect, and a 3-mm relative proptosis measured with a Hertel-style exophthalmometer, which did not increase with Valsalva maneuver. Ocular motility showed mildly reduced left abduction. Anterior segment examination was normal. Posterior segment examination demonstrated temporal optic disc pallor on the left and grade 2 hypertensive retinopathy bilaterally. The OCT retinal nerve fiber layer was unable to be obtained for the left eye due to poor fixation, but there was evidence of ganglion cell atrophy at the left macula. OCT findings for the right eye were consistent with hypertensive changes.
After review of her CT and MRI, a primary orbital arterial or arteriovenous anomaly with subsequent thrombotic or ischemic sequelae was suspected. She was admitted for a trial of intravenous methylprednisolone 1 g daily for 3 days for any inflammatory component of her left optic neuropathy. Digital subtraction angiography demonstrated a slow-filling, tortuous dilated aneurysm of the entire intraorbital segment of the left ophthalmic artery (shown in Fig. 1a) corresponding to the left orbital vascular structure seen on CT (shown in Fig. 1b) and MRI. In addition, digital subtraction angiography demonstrated multifocal vascular abnormalities including other intracranial and extracranial fusiform aneurysms (shown in Fig. 2). Nonspecific vasculopathy, collagen-vascular anomalies, and large vessel vasculitis were all considered; CT angiogram of the chest, abdomen, and pelvis was performed, and it did not demonstrate additional vascular abnormalities. Autoimmune screen including complement C3, C4, rheumatoid factor, cyclic citrullinated peptide antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigen antibodies, antinuclear antibodies, and double-stranded DNA antibodies was normal.
The patient's visual acuity remained as no perception of light despite a trial of methylprednisolone. No other specific interventions were pursued, given that the damage to her left optic nerve was deemed irreversible. Her antihypertensive regimen was optimized, and she was counseled regarding smoking cessation and alcohol intake reduction by drug and alcohol services. Genetic testing was strongly recommended to investigate genetic syndromes including polycystic kidney disease, fibromuscular dysplasia, connective tissue disease, neurocutaneous syndromes, and vasculitis, but the patient declined to proceed. Follow-up appointments by ophthalmology, neuro-interventional radiology, complex vascular anomaly service, cardiology, medical genetics, and rheumatology were planned. However, the patient has failed to attend any of her scheduled specialist appointments at the time of writing despite efforts from multiple specialties to make contact. | compressive optic neuropathy, intraorbital aneurysm, ophthalmic artery, ophthalmic artery aneurysm | Not supported with pagination yet | null |
PMC10286156_01 | Male | 29 | A 29-year-old Canadian male of Indian descent without a significant past medical history presented to the emergency department (ED) in Tucson, Arizona directly from a local optometry office after significant bilateral papilledema was noted on a routine exam required for an updated prescription for his corrective lenses. He denied nausea, vomiting, eye pain, and acute vision changes. However, he endorsed ongoing headaches for 6 months, initially starting in late spring following a job interview for a materials engineer position at a nearby mine and exploring other Sonoran Desert attractions in Arizona earlier in the year. He reported briefly living in India 4 years prior to presentation but was otherwise without notable travel history or high-risk social behaviors. He repeatedly presented to local EDs in Canada and underwent neuroimaging for his new-onset, severe headache postjob interview. Head computerized tomography (CT) and magnetic resonance imaging (MRI) during those visits revealed no acute abnormalities. At these ED visits, he was treated for migraines before discharging home. The patient also reported a 20-pound weight loss in the following months, but his weight stabilized and headache improved gradually after relocating to Arizona for his new job.
In our ED, a CT of the head showed ventriculomegaly with hydrocephalus (Figure 1A). Subsequently, an MRI of the brain confirmed extensive basilar meningeal enhancement with communicating hydrocephalus (Figure 1B). Neurosurgery was immediately consulted based on neuroimaging results. Following a successful lumbar puncture (LP), the patient was initially treated empirically for viral, fungal, bacterial, and mycobacterial meningitis, given his degree of hydrocephalus and hyperdense basilar meningeal enhancement on neuroimaging.
Initial cerebrospinal fluid (CSF) studies showed low glucose (19 mg/dL), elevated protein (279.8 mg/dL) with lymphocytic predominant leukocytosis (87% of 335 per microL), and an opening pressure of 33 cmH2O. Empiric coverage was narrowed to cover Mycobacterium tuberculosis and Coccidiosis spp. based on his international travel history and endemic exposure. Cerebro spinal fluid Gram stain did not visualize any organisms, spherules, molds, or yeasts. Bacterial and fungal cultures of CSF fluid did not yield any growth. Diagnosis of disseminated coccidioidomycosis meningitis was confirmed with positive Coccidioides enzyme immunoassay (EIA) IgG antibody, positive Coccidioides immunodiffusion (IMDF) IgM tube precipitin antibody, positive Coccidioides IMDF IgG complement fixation (CF) antibody, serum Coccidioides CF titer of 1:128, and CSF Coccidioides CF titer of 1:32. Computed tomography thorax imaging also identified a 3-mm left lower lobe pulmonary nodule without parenchymal consolidation, cavitary lesion, or pleural effusion (Figure 1C).
Our patient was treated with intravenous amphotericin B for 5 days with concurrent intravenous fluconazole until therapeutic azole levels reached blood-brain barrier penetrance concentrations. Consistent with Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines, our patient was advised to undergo ventriculoperitoneal (VP) shunt surgery with neurosurgery for definitive management of symptomatic hydrocephalus. However, he declined any invasive procedure due to his perception that his symptoms were not hindering his ability to perform his highly demanding occupational and daily activities. He was transitioned to oral fluconazole before discharging home with close outpatient follow-up in subspecialty clinics while waiting to establish care with a primary-care physician. Prior to discharge, he was educated on warning signs and symptoms (including but not limited to visual changes, new neurological symptoms, urinary or bowel dysfunction, worsening headaches, refractory nausea, and vomiting) and given strict ED return precautions. He was also scheduled for a repeat outpatient brain MRI 3 months postdischarge.
Since discharge, he has been closely monitored for any progression of his intermittent headaches or further clinical signs of neurologic impairment and completed repeat brain MRI imaging (Figure 2A-C). Thus far, our patient endorses a positive response to and tolerance of oral fluconazole treatment with symptomatic and radiographic improvement. | coccidioidomycosis study group, idsa, coccidioidal meningitis, communicating hydrocephalus, ventriculoperitoneal shunt | Not supported with pagination yet | null |
PMC4840426_01 | Male | 65 | A 65-year-old Japanese male was admitted to our hospital with a productive cough and progressive dyspnea. His comorbidities were hypertension and T2DM; therefore, he regularly received some medications. Several days before the appearance of his chief complaints, vilidagliptin (100 mg/day) was started for uncontrolled T2DM. His respiratory condition gradually worsened over about two weeks.
On hospital admission, his vital signs were as follows: body temperature 35.8 C, blood pressure 120/79 mmHg, heart rate 66 bpm, and oxygen saturation 98% under 2 L/min of oxygen. On physical examination, the patient had fine crackles in both lung fields on chest auscultation. There were no physical signs suggestive of collagen vascular diseases. The laboratory tests showed high levels of serum immunoglobulin E (IgE: 4216 mg/dl, normal range<400 mg/dl) and Krebs von den Lungen-6 (KL-6: 9781 U/ml, normal range<500 U/ml). Examination of autoantibody titers, including anti-nuclear antibody, anti-ribonucleoprotein antibody, anti-smith antibody, anti-Ro/SSA antibodies and anti-La/SSB antibodies, as well as anti centromere antibody, anti-topoisomeraseI antibody, anti t-RNA synthetase antibody and serum complement, demonstrated that all were within normal range. Arterial blood gas analysis on 2 L/min of oxygen revealed respiratory alkalosis (pH: 7.450, PaO2: 111.6 Torr, PaCO2: 32.1 Torr, HCO3-: 21.8 mmol/L). A chest radiograph showed reduction of bilateral lung-volume and reticular shadows in all lung fields (Fig. 1a). Chest computed tomography (CT) demonstrated extensive ground-glass opacity (GGO) with associated irregular reticulation throughout both lungs. The distribution of interstitial shadows was peribronchovascular and basal dominant (Fig. 1b and c). Pulmonary function test (PFT) revealed a restrictive defect; forced vital capacity (FVC) was 43.2% of the predicted value. Flexible bronchoscopy showed normal airway anatomy. Bronchoalveolar lavage (BAL) fluid revealed inflammatory changes with a cell differential count of 23% macrophages, 57% lymphocytes, 5% neutrophils, and 12% eosinophils. Microbiological studies of BAL fluid were negative. Transbronchial lung biopsy (TBLB) was performed and biopsy samples were obtained from both the left upper and lower lobes. Biopsy specimens of the lung showed atypical and multinucleated regenerative alveolar epithelial cells, and infiltration of eosinophils, lymphocytes and plasma cells was observed (Fig. 2a). Interstitial fibrosis was seen both in the alveoli and around the thickened alveolar walls (Fig. 2b). These findings of TBLB specimens were consistent with subacute interstitial pneumonia, which is an organizing pneumonia with an acute alveolar injury pattern. In addition, the drug lymphocyte stimulation test (DLST) for vildagliptin was positive. From these results, we diagnosed the patient as having vildagliptin-induced interstitial pneumonia.
Vildagliptin was discontinued on the day that the patient was admitted (day 20) and glucocorticoid therapy was initiated on day 27 (Fig. 3). The respiratory condition and GGO findings on chest CT gradually improved after glucocorticoid treatment was started. The patient was discharged on day 75. The patient continues to take his regular his regular medications except vildagliptin, and has had no recurrence. | bal, bronchoalveolar lavage, ct, computed tomography, dlst, drug lymphocyte stimulation tests, dpp-4 inhibitor, dpp-4, dipeptideylpeptidase-4, drug-induced lung injury, fvc, forced vital capacity, ipaf, interstitial pneumonia with autoimmune features, ige, immunoglobulin e, kl-6, krebs von den lungen-6, pft, pulmonary function testing, t2dm, type 2 diabetes mellitus, tblb, transbronchial lung biopsy, vildagliptin | (b and c) Chest computed tomography showed extensive ground-glass opacity including irregular reticular opacity in both lung fields. The distribution of interstitial shadows was peribronchovascular and basal dominant. |
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PMC4840426_01 | Male | 65 | A 65-year-old Japanese male was admitted to our hospital with a productive cough and progressive dyspnea. His comorbidities were hypertension and T2DM; therefore, he regularly received some medications. Several days before the appearance of his chief complaints, vilidagliptin (100 mg/day) was started for uncontrolled T2DM. His respiratory condition gradually worsened over about two weeks.
On hospital admission, his vital signs were as follows: body temperature 35.8 C, blood pressure 120/79 mmHg, heart rate 66 bpm, and oxygen saturation 98% under 2 L/min of oxygen. On physical examination, the patient had fine crackles in both lung fields on chest auscultation. There were no physical signs suggestive of collagen vascular diseases. The laboratory tests showed high levels of serum immunoglobulin E (IgE: 4216 mg/dl, normal range<400 mg/dl) and Krebs von den Lungen-6 (KL-6: 9781 U/ml, normal range<500 U/ml). Examination of autoantibody titers, including anti-nuclear antibody, anti-ribonucleoprotein antibody, anti-smith antibody, anti-Ro/SSA antibodies and anti-La/SSB antibodies, as well as anti centromere antibody, anti-topoisomeraseI antibody, anti t-RNA synthetase antibody and serum complement, demonstrated that all were within normal range. Arterial blood gas analysis on 2 L/min of oxygen revealed respiratory alkalosis (pH: 7.450, PaO2: 111.6 Torr, PaCO2: 32.1 Torr, HCO3-: 21.8 mmol/L). A chest radiograph showed reduction of bilateral lung-volume and reticular shadows in all lung fields (Fig. 1a). Chest computed tomography (CT) demonstrated extensive ground-glass opacity (GGO) with associated irregular reticulation throughout both lungs. The distribution of interstitial shadows was peribronchovascular and basal dominant (Fig. 1b and c). Pulmonary function test (PFT) revealed a restrictive defect; forced vital capacity (FVC) was 43.2% of the predicted value. Flexible bronchoscopy showed normal airway anatomy. Bronchoalveolar lavage (BAL) fluid revealed inflammatory changes with a cell differential count of 23% macrophages, 57% lymphocytes, 5% neutrophils, and 12% eosinophils. Microbiological studies of BAL fluid were negative. Transbronchial lung biopsy (TBLB) was performed and biopsy samples were obtained from both the left upper and lower lobes. Biopsy specimens of the lung showed atypical and multinucleated regenerative alveolar epithelial cells, and infiltration of eosinophils, lymphocytes and plasma cells was observed (Fig. 2a). Interstitial fibrosis was seen both in the alveoli and around the thickened alveolar walls (Fig. 2b). These findings of TBLB specimens were consistent with subacute interstitial pneumonia, which is an organizing pneumonia with an acute alveolar injury pattern. In addition, the drug lymphocyte stimulation test (DLST) for vildagliptin was positive. From these results, we diagnosed the patient as having vildagliptin-induced interstitial pneumonia.
Vildagliptin was discontinued on the day that the patient was admitted (day 20) and glucocorticoid therapy was initiated on day 27 (Fig. 3). The respiratory condition and GGO findings on chest CT gradually improved after glucocorticoid treatment was started. The patient was discharged on day 75. The patient continues to take his regular his regular medications except vildagliptin, and has had no recurrence. | bal, bronchoalveolar lavage, ct, computed tomography, dlst, drug lymphocyte stimulation tests, dpp-4 inhibitor, dpp-4, dipeptideylpeptidase-4, drug-induced lung injury, fvc, forced vital capacity, ipaf, interstitial pneumonia with autoimmune features, ige, immunoglobulin e, kl-6, krebs von den lungen-6, pft, pulmonary function testing, t2dm, type 2 diabetes mellitus, tblb, transbronchial lung biopsy, vildagliptin | (b and c) Chest computed tomography showed extensive ground-glass opacity including irregular reticular opacity in both lung fields. The distribution of interstitial shadows was peribronchovascular and basal dominant. |
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PMC10090349_01 | Male | 34 | A 34-year-old male came to our hospital for 4 days due to limited extension of his left ring finger after playing basketball. The affected finger was temporarily fixed by splint. X-ray examination was performed to confirm the diagnosis of bony mallet finger (Figures 2A,B). The next day, the patient was treated with the new technique under fluoroscopy (Figures 2C,D). Postoperative X-ray examination was performed (Figures 2E,F). After discharge, the patient was informed to review the X-ray at the outpatient clinic every 2 weeks. X-ray examination 6 weeks later showed that the fracture had healed and the K-wires were removed (Figures 3A,B). Then the patient was informed to review every 4 weeks. The recovery of finger function was evaluated at the last follow-up (Table 1 Patient No. 4, Figures 3C-F). | bony mallet finger, fracture, kirschner wire, phalanx, tendon | Not supported with pagination yet | null |
PMC3412107_01 | Male | 0 | A five-month-old male infant presented with the history of fever and eye gaze from 3 days ago. Fever was mild to moderate without any associated chills.
His birth history as well as developmental history was uneventful. The child was immunized up to date. The mother had no signs of mastitis. The child was apparently asymptomatic until two days before admission.
There was no evidence of other focal deficit, altered sensorium, or seizures. Patient neither swam nor recently took a bath in pond, pool, or lake. All relevant history for tuberculosis was negative.
CBC showed WBC 20,500 /mm3 (PMN 65%, lymphocytes 30%, monocytes 1%, eosinophils 1%, band cell 3%), hemoglobin 10.5 g/dL, hematocrit 31.9%, platelet count 731,000 /mm3. Serum electrolyte showed Na = 138, K = 5.7. ESR and CRP were 92 mm/h and 11.3 mg/L, respectively. Stool exam and urine analysis were normal; blood, urine, and stool culture were negative.
A plain and contrast CT revealed communicated hydrocephalus. Following CT, lumbar puncture was done and CSF sent for microbiological and cytological analysis which revealed milky color, 2500 WBC cells/mm3 (PMN = 75%, Lymph = 25%) without any RBC with 391 mg/dL protein and 3 mg/dL of sugar. No bacteria or fungal elements were seen on gram stain. Bacterial culture was negative. Provisional diagnosis of acute bacterial meningitis was made, and the child was treated empirically by intravenous ceftriaxone 100 mg/kg/day and vancomycin 15 mg/kg/dose.
Smear and PCR of CSF for tuberculosis was negative. Four days after starting of vancomycin and ceftriaxone, fever has not decreased so CSF examination was repeated. Second CSF analysis revealed 150 WBC cells/mm3 (PMN = 70%, Lymph = 30%), RBC 500 cells/mm3 with 121 mg/dL protein and 16 mg/dL of sugar. Naegleria Fowleri was seen on microscopic examination of wet preparation of CSF.
Following the demonstration of amoebae in CSF, clinical diagnosis of primary amoebic meningoencephalitis (PAM) was made. Rifampin was started in a dose of 10 mg/kg orally per day and Amphotericin B in a dose of 1 mg/kg/day. CSF culture for Naegleria was also positive.
Three days after beginning of treatment with Amphotericin B and Rifampin, there was improvement in clinical signs and symptoms but fever has not decreased yet, so brain MRI was performed that revealed just hydrocephalus (Figure 1). The patient was referred to the Postgraduate Institute for the insertion of a ventriculoperitoneal shunt. Fever discontinued after surgery. After complete treatment, the patient was discharged. On followup, two months later the patient was totally asymptomatic. | null | Not supported with pagination yet | null |
PMC3883597_01 | Male | 69 | A 69-year-old male patient presented as an outpatient with increased creatinine levels (281 mumol/L) associated with proteinuria (2.5 g/24 h) and hematuria (110 g/L). His history was not unusual and he denied any abuse of alcohol, drugs, or over-the-counter stimulants. Review of his history was negative for any recent fever, rash, contact with sick persons, or acute illness involving the respiratory or gastrointestinal tract. The examination of ANCA and a chest radiograph were unusual. He was diagnosed with ANCA-associated vasculitis after findings of a perinuclear ANCA (p-ANCA) positive reaction (495 U/mL), urine examination, renal insufficiency by creatinine assay, and lung infiltration by CT scan. After starting treatment with cyclophosphamide pulse therapy, sequential therapy with low-dose prednisone (10 mg qid [every other day]), he underwent a 4-year follow-up. During this time, the level of serum creatinine was stable (Figure 1), and both proteinuria and hematuria improved (Figure 2). A chest CT scan was performed, which showed that the lung fibrosis remained unchanged (Figure 3).
However, after the 4-year follow-up, the patient experienced a sudden and rapid deterioration in lung infiltration and exhibited pulmonary hemorrhage (PH) along with a progressively lower hemoglobin (Figure 3). Interestingly, there was not only no increase in creatinine levels (Figure 1), but also a negative conversion of p-ANCA. The galactomannan assay and Mycobacterium tuberculosis antigen-specific interferon (IFN)-gamma release assays (T-SPOT -TB test; Oxford Immunotec Ltd, Oxford, UK) were both negative. After immunosuppressive therapy (methylprednisolone and cyclophosphamide pulse therapy for 1 week), and empirical widened coverage of anti-infective therapy, progressive lung fibrosis occurred, the PH worsened, and he died from respiratory failure. | anca, lung fibrosis, pulmonary hemorrhage, renal insufficiency, vasculitis | Not supported with pagination yet | null |
PMC9390486_01 | Male | 14 | A 14-year-old boy without burdened family, pregnancy and perinatal history. At 3 months of age, he was diagnosed with cytomegalovirus (CMV) and EBV infection with severe hepatitis, which was confirmed by PCR. The boy did not meet diagnostic criteria for HLH. The parameters of humoral and cellular immunity assessed at that time were normal. At the age of 5, he had an episode of diarrhea, followed by pneumonia complicated by a pleural empyema, which required decortication of the left lung. The patient was also highly hypersensitive to insect bites [Figure 1A]. In repeated immunology tests at the age of 5, agammaglobulinemia was observed (IgG 0.5 g/l; IgA <0.06 g/l; IgM 0.12 g/l), the percentage and absolute number of CD19+ cells were normal for the primary lymphocyte subpopulations, the CD3+CD4+/CD3+CD8+ ratio was inverted. In our case NK studies were not performed. In addition, a decreased percentage of memory switched B cells was demonstrated. Genetic tests using the next-generation sequencing method (NGS) were carried out at the age of 13. A mutation in the TNFRSF13B gene was detected, which resulted in defective production of the TACI protein. Thus, the diagnosis of the heterozygous variant of CVID was confirmed and a heterozygous variant in the STX11 gene was also demonstrated.
At the age of 5, substitution therapy with intravenous human immunoglobulin was implemented. After one year, subcutaneous infusions were introduced and carried out for 7 consecutive years, without complications. EBV and CMV viremia was not determined at that time.
At the age of 13, an erythematous papular rash occurred on lower limbs and then papulopustular skin lesions were observed, which receded leaving deep scars. Moreover, periorbital edema was also periodically observed. A relapse of new skin lesions was accompanied by high fever. Laboratory tests revealed thrombocytopenia, neutropenia and hypertransaminasemia. After three months, serous-filled vesicles began to appear around the papular erythematous changes [Figures 1B, C]. The skin lesions occurred with periods of exacerbation and remission [Figure 1D]. HHV6, Adenovirus, Parvovirus B 19, VZV, HSV 1, HSV 2, HIV, Aspergillus spp, influenza A, influenza B, RSV, SARS-Cov-2, as well as tuberculosis and other mycobacteriosis were excluded. Staphylococcus epidermidis was cultured from swabs of the vesicles on the scalp. Targeted treatment was applied but with no improvement. At the same time, a rapid increase in EBV viremia (>5X106 IU/ml) was observed. In therapy, 4 doses of anti-CD 20 monoclonal antibodies (rituximab) were used. Rituximab was used before the final diagnosis of T-cell involvement was obtained. A transient reduction in EBV viremia was achieved, but with no clinical improvement. The treatment was followed by a complete depletion of B cells. Additionally, a significantly increased percentage and absolute number of CD3+CD8+ cells (cytotoxic T cells) were noticed. A skin biopsy was performed, and histopathological examination showed features of vasculitis. Therefore, prednisone 1 mg/kg body weight was used in the treatment, however with no clinical improvement. Due to the above, histopathological examination of skin tissue samples was performed in a reference center. The consulting pathologist recognized EBER+ CD8. The images of the histopathology results and their description are presented in Figure 2 [Figure 2]. The child was assessed for T-cell receptor (TCR) clonality in peripheral blood T lymphocytes. The result was normal. PET-CT scanning showed features of scalp involvement, with no changes in the lymph nodes, liver and spleen [Figure 3]. Based on the above clinical presentation and hystopatologic findings the systemic form of HV-LPD from mature cytotoxic T cells infected with EBV was diagnosed. According to the WHO classification fulfilled criteria were presence of general symptoms, hypersensitivity to insect bites [Figure 1A] and no signs of organ involvement (besides skin). The literature analysis showed that the best treatment effects of systemic forms of HV-LPD were achieved in patients in whom the EBV load in peripheral blood was reduced to <200 IU/ml, and then allogeneic hematopoietic cells were transplanted. Based on individual reports, different therapeutic regimens were used in the treatment preparing for HCT, as shown in Figure 4. None of them resulted in the expected decrease in viral load. Additionally, the disqualification of an unrelated donor made it necessary to postpone the planned HCT for another month. For this reason, it was decided to conduct an experimental cell therapy with the use of T cells sensitized by EBV. Before HCT, the boy underwent 2 cycles of immunotherapy with Tabelecleucel (TabCel) (i.v. 2x106/Kg, partially HLA matched) by Atara Biotherapeutics Inc. (Thousand Oaks, CA, USA). TabCel was administered three times in each cycle: on days 1, 8 and 15. The patient tolerated the treatment well, fever appeared on the 6th day after the first administration of the drug. Massive inflammation occurred on the scalp (erythema with subcutaneous swelling, petechiae and dark scabs), which disappeared after one day. Papular eruptions healed quickly with no tendency to deep scar [Figures 1E, F]. These changes were treated as the effect of immunotherapy. No such reactions were observed after subsequent intravenous administrations of the TabCel. Periodically, new HV skin lesions appeared that healed quickly leaving scars, but the general symptoms (fever, swelling) subsided. The EBV viremia did not decrease to the expected value of <200 IU/ml. In the first cycle of immunotherapy, the patient was infected with SARS-CoV-2, which was associated with a short-term fever, cough and increased fatigue that lasted for about 4 weeks. Pneumonia with the involvement of about 10% of the lung parenchyma was diagnosed. The treatment included remdesivir, convalescent plasma and empirical antibiotic therapy, which resulted in stabilization of lung lesions. Complications of COVID-19 were mild myocarditis and arterial hypertension. It was necessary to implement dual antihypertensive therapy (enarenal and metoprolol). COVID-19 and its treatment did not interfere with the implementation of specific immunotherapy. In the 8th week after the end of the 2nd cycle of HV-LPD therapy, conditioning according to Sawada was started and then allogeneic hematopoietic cell transplantation was performed from a 10/10 HLA matched unrelated donor, ABO and Rh incompatible with the recipient. Cyclosporine and methotrexate were used to prevent graft-versus-host disease (GvHD). On the +5 th day after allo-HCT, a single dose of anti-CD20 antibodies was administered. Due to the positive CMV infection status in the recipient and negative in the donor (high risk of CMV reactivation), letermovir was administered prophylactically. Engraftment was achieved on day +24. The early post-transplant period was complicated by gastrointestinal mucositis. No new skin lesions were formed since HCT. In addition, CMV infection was not reactivated and there were no reports of other infections or fever. Since the administration of the conditioning regimen, a gradual decrease in EBV viremia was observed until undetectable levels on day +17. Due to viremia (103 IU/ml) on day +24, it was decided to administer monoclonal anti-CD20 antibodies single dose as pre-emptive therapy. Symptoms of GvHD were not observed. From day +31, 2 consecutive cycles of EBV immunotherapy with specific cytotoxic T cells were administered on days 1, 8 and 15 of each cycle. Immunosuppressive treatment was completed on day + 134 after allo-HCT.
From day +38 to day +300, no reactivation of EBV and CMV was observed. At the time of preparing the paper (approx. +300 after HCT) the patient's condition was good. No clinical signs of HV-LPD recurrence occured but there still were elevated levels of transaminases and gamma-glutamyl transferase (GGT). Hematological parameters were normal, except for a slightly reduced number of platelets (in the range of 70-150 K/microl). The boy required systematic human immunoglobulin supplementation, which was carried out from day +180 by the subcutaneous route. In cyclic determinations of immunoglobulin levels around day +280, an increase in IgM concentration was observed, which may be an indication of reconstruction of humoral immunity. There was also an improvement in the analyzed lymphocyte subpopulations. The percentage of CD19+ cells decreased (3.4%), but their absolute number increased to normal (224/microl). | allo-hct, cvid - common variable immunodeficiency disorders, ebv-ctls, ebv-specific cytotoxic t cells, hv-lpd, ngs - next generation sequencing, allogeneic hematopoietic stem cell transplantation | Not supported with pagination yet | null |
PMC3657446_01 | Female | 9 | A thirty-nine-year-old African American female with no significant past medical history presented to the emergency department cachectic and "feeling sick" for two weeks with generalized fatigue, malaise, and productive cough with hemoptysis. Review of systems was positive for anorexia, unquantified weight loss, nausea, vomiting, and dizziness. She had no history of hypertension, hematologic disorders, or cancers in herself or in her family.
The clinical examination at the time of admission revealed severe pallor and oral candidiasis with the rest of the examination benign. Her mental status was normal and she was alert and oriented to person, place, and time. Medical research scale (MRC) grade was 4/5 in all extremities, likely secondary to deconditioning and severe anemia. The patient's vital signs were normal, including a blood pressure of 122/65 mm Hg.
On admission, laboratory analysis revealed severe abnormalities including blood urea nitrogen (BUN) of 138 mmol/L, serum creatinine of 22.3 mumol/L, hemoglobin of 4.9 g/dL, and hematocrit of 16.4% with a normocytic anemia. Arterial blood gas revealed pH 7.17, pCO2 18.8 mm Hg, pO2 143 mm Hg, and oxygen saturation of 99 percent on room air. The other laboratory parameters including white blood count, chemistry panel, platelets, and liver function tests were within normal limits. Urine toxicology screen and pregnancy tests were negative.
She was admitted to the intensive care unit and placed on droplet precautions until tuberculosis was ruled out. She was given 4 units of packed red blood cells after ruling out reversible causes of blood loss. Gynecologic history included eleven live births with poor antenatal care. During the hospital stay, the patient was diagnosed, for the first time, with new onset ESRD classified as Stage 5 chronic kidney disease. It had gone unchecked and the patient was unaware of any kidney issues. During this admission, She received multiple rounds of dialysis which brought her blood urea nitrogen and creatinine ratio (BUN/Cr) to near normal ranges over 3 days. Also, due to the patient's oral candidiasis her HIV status was checked. HIV ELISA and Western Blot were positive with a CD4 T lymphocyte count of 112 cells/muL and a viral load of 780,000 cells/mm3.
The patient was stable for the first 4 days until she had 2 seizures within 24 hours and became nonverbal, uncooperative, and encephalopathic. By this point, her BUN/Cr was brought down to 25/6.2 from the rounds of dialysis. Her blood pressure during the period of seizure was 152/96 mm Hg, which was thought to be secondary to the seizures, and electrolytes were within normal limits. She responded to painful stimuli, pupils were equally reactive, deep tendon reflexes intact, MRC rated 3/5, and there was no papilledema or neck stiffness. Keppra was started for seizure control.
Computed tomography (CT) without contrast showed white matter hypodensity in the posterior parietal-occipital lobes with the remaining findings within normal limits (Figure 1). A CT performed the following day confirmed the presence of hypodense regions but with newly noted small hemorrhages within the parietal and occipital regions. Magnetic resonance imaging (MRI) without contrast revealed areas of T2 prolongation in the subcortical white matter, predominantly in the occipital and parietal regions with scattered foci of susceptibility artifact bilaterally in the occipital lobes. The largest focus measured 10 cm x 0.6 cm in the left occipital lobe (Figure 2). A repeat MRI with gadolinium showed a stable image with no pathologic enhancement and the foci of hemorrhage remained stable (Figure 3).
Given that PRES is a diagnosis of exclusion and based on clinical and radiographic findings, infectious causes of this acute change in mental status were ruled out. Cerebrospinal fluid analysis showed protein of 164 mg/dL, glucose of 49 mg/dL, 630 RBCs/mm3, 0 WBCs/mm3, and LDH of 37 U/L. No acid fast bacilli were seen. Polyomavirus, herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Toxoplasma Gondii IgG, and VDRL were negative. Two sets of blood and urine cultures were negative. There were no further complications with mental status and her cognitive function recovered completely. The patient's vital signs, hemoglobin, and BUN/Cr were stable when she was discharged to home with follow up at the HIV and renal clinics. | null | Not supported with pagination yet | null |
PMC1142328_01 | Female | 3 | A girl, diagnosed enzymatically for MPS I (McKusick's OMIM (MPS I, Hurler syndrome, Scheie syndrome): 25280) at the age of 3 years and 9 months, was investigated until the age of 5 years and 4 months. Genetic analysis (performed by us) indicated that one allele of the alpha-L-iduronidase gene contains a mutation causing a common Q70X truncation in the enzyme amino acid sequence. Further studies (performed at Consorzio Genetica Moleculare Umana, Monza, Italy, supervised by Prof. Andrea Biondi and coordinated by Genzyme Co.) confirmed the presence of this allele and indicated that the second mutation is an in frame deletion of three base pairs (codon 349), resulting in the loss of aspartic acid residue (Delta349). The investigated MPS I patient suffered, between other symptoms characteristic for this disease, from frequent diarrhea or loose stools, often accompanied by vomiting. No obvious contacts with persons suffering from intestinal infections, including family members (who also had no documented chronic or often diarrhea), were noticed shortly before or during these episodes. During the most severe episodes of diarrhea, detailed microbiological analyses of stools were performed. The patient was never treated with antibiotics before stool collection, thus, results of microbiological assays were not affected by such a treatment. Bacterial, viral or fungal infections were detected in all these analyses (Table 1).
Isolation and preliminary analyses for identification and characterization of bacteria, viruses and fungi were performed using S-F selenium, blood agar, CNA, McConkey, SS, XLD, Sabouraud, Kligler and Singer, and BHI media (purchased from Becton Dickinson, Biomed or Bimex). Detailed analyses were performed using biochemical assay kits ID GN 32 (BioMerieux), EN-COCCUStest (Lachema) and ATB ID 32 C (BioMerieux), and immunological tests (kits purchased from Immunomed and BioMarieux). The microbiological assays were performed according to the semi-quantitative method, described previously. Non-enteropathogenic strains of Escherichia coli, strains of Enterococcus faecalis and small amounts of other bacteria belonging to Enterobacteriaceae were considered as normal aerobic bacterial flora. Identification of enteropathogenic E. coli strains was performed using a specific latex-immunological assay (purchased from Biomex). In this assay, 10 randomly chosen E. coli colonies (classified on the basis of microbiological and biochemical tests described above) were streak onto nutrient agar plates, and following 18 h incubation at 35 C bacteria were tested immunologically using the Biomex kit. The O antigens (characteristic for enteropathogenic E. coli strains but not for other strains of this bacterium), were detectable in this assay, and corresponding strains, bearing particular antigens, were divided into following groups: group A (antigens O26, O55, O111, O127 and O142), group B (antigens O86, O119, O124, O125, O126 and O128) and group C (antigens O18, O25, O44 and O114). | null | Not supported with pagination yet | null |
PMC9650969_02 | Male | 40 | The outbreak of monkeypox in the European region is characteristic of males between 31 and 40 years old, predominantly among men who have sex with men. Although cases outside endemic regions are often linked to international travel, in this outbreak there are no travel links to Africa. Human-to-human transmission occurs by direct contact including during sex, as we described in our case. The clinical presentations in this outbreak are unusual with lesions in the ano-genital region and mild prodromal symptoms. Hence, the disease could be confused with sexually transmitted infections (secondary syphilis, genital herpes, chancroid) or varicella-zoster virus infection. This stresses the importance that dermatologists at outpatient clinics identify and isolate cases early and promptly trace contacts. Dermatologists should remain vigilant, although monkeypox is not a classic venereal disease, it could be transmitted during sexual intercourse. | null | Not supported with pagination yet | null |
PMC6742875_01 | Male | 27 | A 27-year-old professional soccer goalkeeper sustained blunt trauma to his left thigh while diving to catch a football. He immediately developed pain and swelling over the lateral aspect of his left thigh below the greater trochanter. The pain was exacerbated by weight-bearing on the affected limb, radiated into the left gluteal region, and was associated with subjectively reduced range of movement in the left hip joint. He struggled with sprinting, jumping, and diving onto the affected side for the remainder of the match but managed to walk independently off the field of play after finishing the game. There was also an associated swelling over the zone of injury, which progressively increased in size in the hours following the match. The player did not have any other concurrent injuries and did not have any significant medical history. Clinical examination revealed a soft, fluctuant, lobulated mass measuring 5.0 cm x 4.0 cm approximately three finger breadths below the left greater trochanter. The mass was exquisitely tender to touch and located in the plane between the skin and underlying fascia. There was an associated effusion around the mass but no overlying erythema or breach in skin integrity. The skin was not warm to touch compared to the right side. There was no tenderness over the bony prominences of the anterior superior iliac supine, ischial tuberosity, greater trochanter, or iliac crest and no snapping of the iliotibial band over the greater trochanter. The patient had full active range of motion in the left hip and knee joints. Specialist hip tests including flexion abduction and internal rotation, flexion abduction and external rotation, Thomas test, and Ober's test were negative. The patient had a normal gait and did not require any walking aids. Plain anteroposterior and lateral radiographs of the left hip joint and left femur were unremarkable. Magnetic resonance imaging (MRI) of the left thigh revealed a well-circumscribed, lobulated mass measuring 5.2 cm x 4.3 cm x 3.2 cm in size. This was arising from the adipose tissue located between the subcutaneous tissue and fascia immediately inferior to the left greater trochanter (Figs. 1 and 2) and was associated with a surrounding effusion (Fig. 3). There was no other bone or soft-tissue pathology identified on the MRI scan. These clinical and radiological findings were consistent with an acute traumatic fat fracture. The differential diagnosis included the following: Fat fracture, benign tumor (e.g., lipoma), malignant tumor (e.g.,liposarcoma), abscess, and hematoma. The patient was reviewed by the team doctor and sports physiotherapist on the day of injury and commenced onto a supervised physiotherapy program the following day. Initial treatment consisted of resting the affected limb, avoiding any exacerbating positions or maneuvers, and limiting any pressure (e.g., laying on the affected side, tight clothing) over the zone of injury. The patient was commenced on regular non-steroidal anti-inflammatory medication. Physiotherapy consisted of isometric muscle exercises, core strengthening, neuromuscular control activities, cryotherapy, and hydrotherapy. After 3 weeks of conservative treatment, the patient still had persistent pain and tenderness over the lateral aspect of his left thigh and could not participate in any level of training or competitive sporting activity. The patient was further counseled about the likely diagnosis and further management options. These included continuing conservative treatment, acute surgical excision, or delayed surgical excision if symptoms persisted despite further rehabilitation. As a professional soccer goalkeeper, his main treatment priorities were early return to sporting activity and minimal risk of recurrence with diving onto the affected side in the future. The patient elected to undergo acute surgical excision of the traumatic fat fracture. The procedure was performed under general anesthetic with the patient in the lateral decubitus position. A longitudinal incision measuring 6 cm center in length was centered over the soft-tissue mass, and dissection performed through the subcutaneous tissue down to the underlying capsule of the fat fracture. Finger dissection was performed between the underlying muscular fascia and the capsule of the fat fracture. Electrocautery was used to dissect fibrous bands adhering the cystic mass to the underlying fascia. The mass was excised with the surrounding capsule intact (Fig.4). Hemostasis was performed and the wound closed with absorbable sutures. Histological analysis of the excised specimen revealed lobulated and focally degenerate adipose tissue. This was covered by a thick layer of inflamed fibrous tissue which extended into the lesion. There was no evidence of fat necrosis or any neoplastic process. The findings were consistent with the working diagnosis of a fat fracture. The patient was followed up in clinic at 2 weeks after surgery. The pain over the left lateral thigh had completely resolved, and the patient had discontinued all analgesia. The patient had returned to his pre-injury level of sporting function without any problems. On examination, the wound was clean and wellhealed without any evidence of infection. There was no underlying collection or mass palpable, and he had full active range of motion in the left hip and knee joints. He did not require any walking aids and had a normal gait. The patient remained asymptomatic and continued to participate in full sporting activity without any complications at 1-year follow-up and was discharged from clinic at this time point. | acute, fat fracture, pain, surgery, trauma | Not supported with pagination yet | null |
PMC4899883_01 | Male | 17 | A 17-year-old high-school football player fell on his shoulder during practice. When the pain continued for several weeks, the boy saw his primary-care physician, who obtained radiographs that showed a mixed lytic and sclerotic lesion at the inferior border of the body of the scapula with adjacent, disorganized, new bone formation (Fig. 1). These aggressive features prompted further evaluation with MR imaging, which showed a large region of bone-marrow edema and adjacent periostitis that was suspicious for Ewing sarcoma, lymphoma, or infection (Figs. 2A and 2B). The only abnormal activity on bone scan was increased uptake in the body of the scapula.
The youth continued to lift weights and participate in football despite the persistent shoulder pain that was somewhat decreased by the time of his scheduled bone biopsy one week following the MRI. One hour before the biopsy, a screening chest CT for pulmonary metastasis showed smooth periosteal reaction around the inner and outer surfaces of the scapula (Fig. 3A), which would be atypical for an aggressive bone neoplasm. Reformatted coronal oblique images of the scapula also showed a fracture line as an oblique linear lucency through the neck of the scapula (Fig. 3B).
Given the chest CT findings and the patient's slight symptomatic improvement, the biopsy was deferred. The patient was instructed to cease all athletic activity for four weeks and then return for a repeat chest CT, which confirmed healing of the fracture. | ct, computed tomography, mri, magnetic resonance imaging | Not supported with pagination yet | null |
PMC5328914_01 | Male | 62 | A 62-year-old patient with high blood pressure and alcohol-related cirrhosis was admitted from the emergency department with deterioration of his general condition developing for some months. On admission, he had hypothermia and signs of severe sepsis. Laboratory tests showed biological inflammatory syndrome, acute renal failure, troponin with NTproBNP levels at 275 ng/L and 30 749 ng/L, respectively. Transoesophageal echocardiography revealed an acute endocarditis on a narrowed bicuspid aortic valve with both a vegetation and an aortic root abscess. Left ventricular ejection fraction was 30%. Blood cultures (Bact-Alert3D; BioMerieux, Marcy l'Etoile, France) were performed before amoxicillin-clavulanic acid and ceftriaxone injections. The patient was then transferred to the cardiologic ICU. Clinical examination highlighted a regular heartbeat with an inconspicuous systolic aortic murmur, left heart failure and splenomegaly with associated necrosed abscesses, pulse rate at 109/min and blood pressure at 80/49 mmHg. Despite the risk of poor evolution, the patient declined the surgery procedure and progressed to an acute respiratory distress syndrome caused by nosocomial pneumonia. Therapy was replaced by cefepime, amoxicillin-clavulanic acid and gentamicin associated with mechanical ventilation and sedation. The patient remained free from fever, CRP level and leukocytosis decreased. However, the respiratory, renal and hemodynamic functions declined rapidly, making surgery impossible. He finally died 13 days after his admission from septic shock with refractory multiple organ failure syndrome secondary to M. nonliquefaciens acute endocarditis.
Regarding microbiological documentation, five aerobic bottles sampled within the first three days of hospitalization were positive. After 24 h of culture at 37 C in Columbia agar with blood 5%, we identified M. nonliquefaciens using MALDI-TOF spectrometry mass (Bruker Daltonics, Wissembourg, France) with a score = 2.297. This phenotypical identification was confirmed by molecular 16S rRNA gene bacterial sequencing using the primers described by Gauduchon et al.. The 444 pb fragment obtained and compared with GeneBank sequences using the BLAST algorithm (http://www.ncbi.nlm.nih.gov/BLAST) showed 100% identity with M. nonliquefaciens strain V0542163 (GeneBank accession n KC866286.1). Rapid detection of beta-lactamase by chromogenic test was positive. In vitro susceptibility tests were performed using the disc diffusion method on Mueller-Hinton blood agar (Difco, Becton Dickinson, Le Pont de Claix, France) with 5% lysed horse blood. As recommended by CA-SFM 2016 (Comite de l'Antibiogramme de la Societe Francaise de Microbiologie; http://www.sfm-microbiologie.org), the breakpoints described for Moraxella catarrhalis were used to determine the susceptibility of this bacterium. This strain was susceptible to amoxicillin-clavulanic acid, cefotaxime, erythromycin, minocycline, nalidixic acid, ciprofloxacin and resistant to trimethoprim/sulfamethoxazole. | 16srrna pcr, endocarditis, fatal issue, maldi-tof, moraxella | Not supported with pagination yet | null |
PMC8346294_01 | Female | 25 | A 25-year-old healthy woman presented complaining of distortion and a blind spot near the central vision of her left eye of one month duration. One week preceding visual symptom onset, she endorsed night sweats, headache, and new-onset anosmia. The night sweats and headaches lasted 3 days. The anosmia lasted 2 weeks. She had multiple confirmed ill COVID-19 contacts at her workplace before the onset of her symptoms. Best corrected visual acuity was 20/20 and 20/25 in the right and left eyes, respectively. Intraocular pressures, previously documented as normal, were 20 mmHg on the right and 24 mmHg on the left after one month of topical difluprednate therapy. The anterior chambers were both quiet with no cell or flare. Examination of the vitreous revealed rare cell and no haze in both eyes. Dilated fundus examination revealed placoid lesions in the macula and midperiphery of both eyes. Peripheral punched-out scars with Schlaegel lines were also noted. Fundus imaging (Figure 1) demonstrated hypoautofluorescent lesions in the macula and midperiphery of both eyes with irregular hyperautofluorescent borders. Hypofluorescent lesions were observed on indocyanine green angiography in a distribution more widespread in the left eye than appreciated on fundus examination. Fluorescein angiography (FA) demonstrated early progressive staining and leakage from the placoid lesions without significant early blockage. Optical coherence tomography demonstrated bilateral outer retinal disruption (Figure 2). Laboratory evaluation was negative for QuantiFERON-TB gold, HIV, and syphilis antibodies. COVID-19 antibody testing returned positive for IgG. COVID-19 PCR testing was not performed. The patient's systemic symptoms had occurred 4 months following the initial pandemic lockdowns in the United States when the patient's county of origin had reported a total of 450-460 cases per 100,000 inhabitants. Neuroimaging was not pursued due to the resolution of headaches and absence of neurologic symptoms at the time of evaluation. She was treated with a taper of oral prednisone starting at 60 mg. The retinal lesions did not progress, and steroid-sparing therapy with azathioprine (1.5 mg/kg) was initiated at 3 weeks. Visual acuity remained 20/20 in both eyes at 10-month follow-up after completing a 3-month oral prednisone taper and continuing azathioprine. | null | Not supported with pagination yet | null |
PMC7468372_01 | Male | 44 | A 44-year-old male presented with sudden onset, diminution of vision in both eyes for 10 days. He gave history of fever, myalgia, and weakness one week prior to onset of ocular problem. He was previously healthy, not known to have diabetes mellitus or hypertension. There was no relevant family or social history of medical significance. During clinical evaluation and laboratory investigation for fever; typhoid, malaria, tuberculosis, syphilis, collagen vascular disease and bleeding disorders were absent. He was diagnosed to have dengue fever as NS1 antigen and IgM antibody were positive. After conservative management, his platelet count had improved from 49x103/microL to 176x103/microL (normal range, 150-450x103/microL) over a week period. At presentation, his best-corrected visual acuity was 1/60 in the right eye (OD) and 6/18 in the left eye (OS). Anterior segment findings were normal. Fundus examination revealed vitritis, perivascular exudates, intraretinal hemorrhages, macular edema, peripapillary retinal whitening, and cotton wool spots in both eyes, with additional retinal whitening affecting the right macula (Figure 1). Fundus fluorescein angiography revealed disc and perivascular leakage limited to posterior pole along with patches of blocked fluorescence. In addition, there was capillary nonperfusion due to occlusion of multiple small arterioles supplying the macula of the right eye confirming macular ischemia (Figure 2). Optical coherence tomography of both eyes demonstrated macular edema with subretinal fluid. A diagnosis of bilateral retinal vasculitis with right eye macular infarction was made. Echocardiography and carotid Doppler studies revealed normal cardiac and carotid artery status. The patient was treated with intravenous methylprednisolone which was futile even after three days of treatment. Then he was counseled for treatment with immunoglobulin, which the patient refused and left for a second opinion without returning back to us. | dengue fever, macular infarction, retinal artery occlusion, thrombocytopenia, vasculitis | Not supported with pagination yet | null |
PMC4748756_01 | Male | 84 | An 84-year-old male was admitted to our respiratory ward on November 23 last year because of intermittent fever with maximum temperature not exceeding 38.5 centigrade for more than 10 days, accompanied by cough with sputum and fatigue. He was a retired army pilot and a nonsmoker. He was treated with acetylcysteine due to PF detected by annual physical examination 5 years ago, with a coexistent anterosuperior mediastinal mass, which did not show much progression. He also had a past history of diabetes for 20 years.
On admission, his temperature was 37.6 centigrade. On physical examination, a fine moist rale over both lower lung fields was noted. Skin exam did not reveal any rash. Musculoskeletal exam revealed no joint swelling or tenderness and he had no edema of the limbs. Neurological exam was normal.
Complete blood count showed eosinophilia with an absolute value of eosinophils of 1.71 x 109/l (13%). Renal function tests were normal (urea 4.5 mmol/l, creatinine 97 mumol/l) on admission. C-reactive protein was 47.7 mg/l. Chest X-ray revealed thickened lung marking in both lower lung fields (fig. 1a). Empirical antibiotics treatment with amoxicillin potassium and doxycycline was used and was changed to piperacillin tazobactam and then tienam but the patient's symptom did not resolve. Blood culture, sputum culture, respiratory virus, sputum acid-fast bacillus smear, Streptococcus pneumoniae antigen, corps antigen, Mycoplasma pneumoniae DNA, tuberculosis DNA and tumor markers were all negative. Complement component C3 was 0.73 g/l and immunoglobulin G (IgG) was 17.94 g/l. Antinuclear antibodies and anti-double-stranded DNA antibodies were negative. Indirect immunofluorescence revealed perinuclear ANCA positive with anti-MPO ANCA specificity by ELISA (125 RU/ml, normal <20 RU/ml); immunofluorescence for cytoplasmic ANCA, and ELISA for antiproteinase 3 ANCA were negative, but anti-GBM antibodies titer (ELISA) was positive at a titer of 1:32. Tuberculosis screening for bronchoalveolar lavage fluid via bronchoscope was negative. Chest CT scan showed honeycombing, reticular and ground glass opacities in the lower lung fields (fig. 1b). Pulmonary function was roughly normal. Lung biopsy showed eosinophilia with vasculitis changes and granuloma formation (fig. 2). During his stay, the renal function was deteriorated (creatinine gradually increased to 171 mumol/l). Percutaneous renal biopsy was performed and immunofluorescence microscopy disclosed linear staining of glomerular capillary basement membrane for IgG and C3, diagnostic for anti-GBM disease (fig. 3).
Diagnosis of AAV with coexistent anti-GBM disease in the patient with acute pulmonary-renal syndrome and long-existing PF/anterosuperior mediastinal mass was made. The patient was then given a regimen consisting of i.v. methylprednisone (80 mg/day) with i.v. cyclophosphamide 0.4 g every week and plasmapheresis (PE) every other week for 6 times. Perinuclear ANCA/anti-MPO ANCA returned to normal 1 week later but anti-GBM antibodies were still positive with the same titer. The symptoms disappeared without relapse. Steroids were then tapered to 60 mg/day. Unfortunately, the patient experienced shortness of breath, palpitation and hypotension during PE, ongoing continuous bleeding from the puncture point of the femoral vein with a dramatic drop of platelet count (32 x 109/l at the lowest), which suggested the diagnosis of heparin-induced thrombocytopenia (HIT). Bilateral lower extremity compression ultrasonography was applied in this patient to rule out silent deep vein thrombosis. PE was discontinued and rivaroxaban was used until the platelet count returned to normal. Anti-GBM antibody was still positive and renal function did not ameliorate after 3 weeks of cyclophosphamide. Therefore, immunosuppressant was switched to rituximab 700 mg/week. Anti-GBM antibody turned to negative after 1 month and creatinine decreased to 149 mumol/l. Mycophenolate mofetil with the dosage of 1.5 g/day was then used for maintenance treatment and oral prednisone gradually decreased to 25 mg/day.
At the latest follow-up visit after around 4 and a half months' treatment, all the antibodies remained negative and creatinine was 123 mumol/l. Repeated chest CT revealed a novel nodule in the upper lobe of the left lung (0.9 x 1.0 cm) with concomitant mild progression of interstitial changes. A further PET/CT showed the novel lesion with a standardized uptake value of 3.0 suggesting inflammatory pseudotumor. Meanwhile, the anterosuperior mediastinal mass was remarkably diminished without thymectomy intervention (fig. 4). | anti-glomerular basement membrane antibody, mediastinal mass, myeloperoxidase-antineutrophil cytoplasmic antibody, pulmonary fibrosis, vasculitis | CT scan. on admission. b; Chest CT scan showed honeycombing, reticular and ground glass opacities in the lower lung fields (arrows). |
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PMC5954791_02 | Male | 17 | A 17 year old male patient presented after a motorcycle accident where he was not wearing a helmet. Upon his arrival at the hospital with a diagnosis of TBI (traumatic brain injury), he was evaluated by the Department of Neurosurgery who decided to treat the patient with a decompressive craniotomy. A CT was done to complete the diagnosis and plan the surgery. The patient had a bifrontal 20 cm cranial defect from the temporal fossa of one side to the other and 10 cm vertical distance (Fig. 4). The thickness of the implant in this case was of 6 mm. It is 1 mm thicker than that of the previous case due to patient anatomic differences in diploe thickness. After surgery, he remained hospitalized for 2 weeks before discharging him. He was referred to us after 3 months of physical therapy once the Neurosurgical Department considered cranial reconstruction feasible. The patient was evaluated and was found to have no neurologic damage and an intact scalp. The patient was deemed an excellent candidate for the placement of a 3D PMMA pre-operative manufactured cranial prosthesis, 2 days after which the patient had a good evolution and was discharged. After 2 months, the patient returned to his normal school activities.
In Mexico these procedures have to be payed in full by the patient, limiting their reach and practice in the general population since they are costly. A customized titanium implant costs around US$5000, and those made from PEEK around US$7000 or more depending on their size. The customized prostheses proposed by the authors have a cost of about US$600, including the digital design, printing of a 3D prototype and the PMMA prosthesis itself. Both titanium and PMMA are the most commonly used alloplastic materials.
The CT scan data is stored in the standard format DICOM (Digital Images and Communications in Medicine) which allows generating an interface between the medical equipment and any other device to visualize the images. Through the DICOM viewer, Osirix generated a three-dimensional reconstruction of all the CT cross-sectional images. A bone filter is applied in order to only observe the bone structure, achieved by taking as reference its attenuation degree.
The implant is generated using the software of the computer-aided design (CAD) ZBrush 4R5 since Osirix is only a viewer.
The implant piece, Vimplant, is generated from the CT skeletal reconstruction of the patient's cranium. With volumetric reconstruction, Vtotal, and considering its symmetry; an imaginary division is made on the sagittal plane, obtaining two volumes, Vleft and Vright. A boolean operation is applied to the volumes Vleft and Vright: Vimplant = Vleft - Vright (Fig. 5).
The implant design must have a precise shape and volume according to each patient's cranial anatomy. Finally, the data is exported in a stereolithography extension file (STL) and fed to the printer.
A CUBE 3D (from 3D System) printer is used to print out a PLA prosthesis from the STL file using a fused deposition model by means of a 1,75 mm filament at a 260 C extruder temperature (Fig. 6). Once the printing process is finished, which takes about 20 h, the scaffolds are removed with a low-speed motor and a carbide bur and the adjustment is verified (Fig. 7). The prosthesis is then taken to the dental laboratory.
The prosthesis is placed in metal containers to obtain two plaster impressions (an internal and an external surface impression). A transparent PMMA OPTI-CRYLR is poured into the space created by the internal plaster impression and pressed with the external mold. The casts are opened and the prosthesis is revealed after a 25-min polymerization time (Fig. 8). The prosthesis is then cut, perforated, and polished with a low-speed motor. Precise anatomical compliance to the model is verified and approved by the multi-disciplinary team (including the neurosurgeons), and the prosthesis is then placed on a mannequin for academic and illustrative purposes (Fig. 9). After obtaining the prosthesis in the laboratory, it is washed with normal saline solution and then submerged in a chlorine based antiseptic solution (Microdacyn 60 by Oculus lnnovative Sciences in Petaluma, CA.) for 15 min before taking it to the hospital where it is sterilized with ethylene oxide gas before its implantation (Fig. 10).
Cranioplasties were carried out 3 months after craniotomy in conjunction with the neurosurgeons. The prostheses were then placed over each of the defects to adjust them in vivo with minimum adjustments with the same low-speed electric motor, and fixed with 3 long titanium bridge plates, each held down with 2 screws (Fig. 11). The procedure ended without any unexpected events. The patients were hospitalized for 2 days and discharged after a single drain is removed from each patient to continue their care as outpatients (Fig. 12).
The patients were evaluated every week for 6 months to register PMMA behaviour, biological sefety and any eventualities (Fig. 13). | cranial implant, cranial vault reconstruction, cranioplasty, low cost prosthesis 3d printing, pmma prosthesis, polymethylmethacrylate resin, skull defects | Not supported with pagination yet | null |
PMC9131087_01 | Female | 63 | We report a case of a large, ulcerating proliferating trichilemmal cyst in a 63-year-old woman, with clinical, radiological, macroscopic, and microscopic correlation. The outbreak of the Coronavirus pandemic delayed her treatment. We review the literature on proliferating trichilemmal cysts, which are relatively rare tumors, which generally are considered benign. However, we found a high rate of malign cases, which stresses the importance of rapid surgical excision and histological diagnosis. Even though our proband had delayed treatment, the tumor did not transform to a malignant form.
Introduction
Proliferating trichilemmal cysts (PTCs) are relatively rare tumors that may appear all over the body but most frequently on the scalp in middle-aged women (1). PTCs occur in a benign and malignant form, but the differentiation between malignant PTC and benign PTC has been debated, implying that all PPT should be treated with the expectation that it could transform into a malignant tumor (2). There are no absolute clinical criteria that can differentiate between benign and malign PTC, why surgery is necessary to give a correct histopathological diagnose. The malignant form may metastasize (3). | case report, corona, lipoma, pilar tumour, proliferating trichilemmal cyst, trichilemmal cyst | Not supported with pagination yet | null |
PMC9131087_02 | Female | 63 | We here report the case of a 63-year-old woman with a large PTC, where surgical treatment was delayed due to the outbreak of the Coronavirus pandemic and a review of the relevant literature on PTCs.
Case description | case report, corona, lipoma, pilar tumour, proliferating trichilemmal cyst, trichilemmal cyst | Not supported with pagination yet | null |
PMC5749271_01 | Male | 78 | Mr. A. is a 78-year-old man with a late-onset Bipolar I Disorder (DSM-5) that started at the age of 64. The onset was with a hypomanic episode characterized by easy irritability, anger, and hyperactivity in work and social life. No specific treatment was necessary at that time. The first manic episode was several years later, at the age of 76, with mood swings, psychomotor hyperactivity, increased levels of energy, and delusions. Mr. A. was hospitalized for the first time and treated with valproate (1000 mg/day). During the following months, Mr. A. showed mood instability with subclinical episodes of depressed mood, apathy, anhedonia, and clinophilia. However, he was no longer on pharmacological treatment. He was admitted again to a psychiatric hospital at the age of 78, after 3 months of apparent well-being. He had a manic episode, characterized by elevated and irritable mood, reduced need for sleep, pressured speech, racing thoughts, distractibility, disorganized behaviours, and auditory and visual hallucinations.
These symptoms started abruptly one week before hospitalization. His family reported that at home he showed fluctuating levels of consciousness and incoherent speech. He also had outbursts of anger and destructive behaviours. After hospitalization, Mr. A.'s symptoms persisted despite acute treatment with valproate (1000 mg/day), quetiapine (75 mg/day), and lorazepam (2.5 mg/day). As part of the clinical evaluation, the patient had a work-up to rule out medical or neurological causes for his condition. A specialist in internal medicine and a neurologist evaluated Mr. A. but no acute medical or neurological signs and symptoms were found. They decided to continue the medications he was taking at home for the diagnoses of hypertension, hypercholesterolemia, Barrett's oesophagus, and a mild benign prostatic hypertrophy. His medications included bisoprolol (2,5 mg/day), alfuzosin (10 mg/day), enalapril (20 mg/day), hydrochlorothiazide (12,5 mg/day), ticlopidine (250 mg/day), and pantoprazole (20 mg/day). A computed tomography (CT) scan was performed. Chronic ischemic changes and mild ventricular dilatation were found but considered as compatible with old age. Electroencephalographic (EEG) results showed poor alpha waves and mild cortical dysfunction. The neurologist concluded that these were findings frequently seen in elderly patients and not related to the acute condition. Acute metabolic syndromes were also excluded: all blood examinations, including blood count, serum glucose, sodium, potassium calcium, magnesium, chloride, and phosphates, were within normal ranges. Vitamin B12 and folate were also normal. Blood culture, urine culture, and VDRL (venereal diseases research laboratory) testing were negative. No substance use, abuse, or withdrawal were diagnosed. Neuroleptic malignant syndrome and serotonin syndrome were considered but excluded as no pyrexia, autonomic instability, or marked rigidity was detected. A diagnosis of delirious mania was made. Over the first seven days of hospitalization, Mr. A. showed a state of partial orientation, with fluctuating cognition, hyperactivity with purposeless activities. On better days, Mr. A. was able to answer the simpler questions with regard to orientation to place and person. In these intervals, the patient had nearly normal speech and thought processes with only occasional racing thoughts. During the worst days, he was noted mumbling to himself, apparently busy without clear goals, often shouting, and frightened by auditory and visual hallucinations. After 12 days of hospitalization, Mr. A. had a syncope episode with release of faeces and urine, followed by a quick recovery of consciousness. The neurologist was alerted again. An acute ischemic transitory attack was excluded. An EKG was performed together with the search for markers of heart necrosis but all tests were negative. The monitoring of pressure levels for the subsequent hours revealed that the patient had in clinostats average arterial blood pressure (PA) of 100/70 mmHg with an average heart rate of 78; in orthostats PA was 95/70 with average heart rate of 90. Most of the antihypertensive therapy was stopped, maintaining only bisoprolol (2.5 mg/day). A cardiac Holter, a pressure Holter, an echocardiogram, and an echo-colour-Doppler of the carotids were performed. The carotid echo-colour-Doppler showed a mild degree of bilateral stenosis, but again not significant from a clinical point of view.
In the subsequent 3 days, temporally related to a progressive rise in pressure values (stabilized around 130/80 with regular heart rate), and with no changes in psychopharmacological treatments, the patient showed a marked improvement, with reduction of psychomotor agitation and normalization of behaviour. Mr. A.'s irregular sleeping patterns were normalized and he was able to sleep through the night. The disorientation resolved completely. He became stable enough for discharge to outpatient care on quetiapine, valproate, and lorazepam at fixed dosages. After considering delirious mania and his lack of response to standard therapies, including lorazepam, we hypothesized that the resolution was due to the discontinuance in antihypertensive medications and to the subsequent normalization of blood cerebral perfusion. | null | Not supported with pagination yet | null |
PMC7670254_01 | Female | 10 | We present a 10-year-old girl who received allogeneic hematopoietic stem cell transplant (HSCT) for Philadelphia chromosome (Ph)-positive acute lymphoblastic leukaemia (ALL) and subsequently developed cytomegalovirus (CMV) encephalitis, successfully treated with CMV-hyperimmune globulin (Figure 1).
The girl was diagnosed with ALL one year prior, and as a result of the positivity for the Ph chromosome, she underwent HSCT in first complete remission. The virological screening performed during the pre-transplant workup by quantitative polymerase chain reaction (PCR) showed a CMV viral load of 4.0 x 103 copies mm-3. The patient received antiviral treatment with ganciclovir, obtaining a complete virus clearance in a few days. Immediately before the HSCT, ganciclovir was replaced with valganciclovir.
After total body irradiation (TBI)-based myeloablative conditioning, the girl received 4.8 x 108 kg-1 bone marrow total nuclear cells from the 10/10 HLA-matched, CMV-positive, unrelated donor. Graft-versus-host disease (GVHD) prophylaxis was performed with tacrolimus and mycophenolate mofetil. The patient received continuous antiviral prophylaxis with valganciclovir, except between days -1 and +20. Neutrophil and platelet engraftment were achieved at day +15 and day +22, respectively. The peripheral blood chimerism analysis at day +30 proved full donor chimerism, and the absence of BCR/ABL transcript in the bone marrow cells confirmed the complete molecular remission.
The patient could not start the maintenance treatment with tyrosine kinase inhibitors because of suboptimal graft function. She showed a marked lymphocyte depletion with a total lymphocyte count of 206 mm-3, CD3 4 mm-3, CD4 2 mm- 3, CD8 1 mm- 3 and CD19 4 mm- 3 at day +150. For this reason, and because the loads of CMV, Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and BKV remained low, the immunosuppressive regimen was discontinued.
At day +164, she developed a persistent headache and high blood CMV, EBV, HHV6 and BKV virus loads were detected. Valganciclovir was shifted to foscarnet. Magnetic resonance imaging (MRI) of the brain did not show central nervous system (CNS) involvement.
Despite the rapid viral blood clearance, the headache worsened, and severe fatigue developed. To rule out CNS disease relapse, at day +178, a lumbar puncture was performed. The cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis (68 cells mm-3), slightly elevated protein level (49 mg dL-1) and normal glucose level (39 mg dL-1), without evidence of blast cells (CD19+CD58+CD10++) on flow cytometry. Tests for CSF toxoplasma, panfungal PCR and JC virus (JCV) were negative. The CSF specimen was stored at -80 C, pending some other diagnostic hypotheses, and the girl continued her outpatient antiviral treatment with valganciclovir.
At day +203, the patient presented with high fever and further worsening headache and fatigue. Lansky performance status decreased from 100% to 60%. A second MRI, serum C reactive protein (CRP) and all viral blood determinations were negative, while the total lymphocyte count increased to 2000 mm-3 with > 600 CD3 mm-3 and > 200 CD4 mm-3. At day +210, the girl was admitted because of fourth cranial nerve palsy with vertical diplopia and positive Bielschowsky test. A brain MRI showed multiple focal lesions with T1 hypointensity and diffusion hyperintensity without enhancement after contrasting medium administration. These findings were suggestive of an immune reconstitution inflammatory syndrome (IRIS). Quantitative PCR on CSF for CMV, EBV, all herpesviruses, JCV, toxoplasma and panfungal PCR was performed and showed a very high CMV load (7.3 x 105 copies mm-3), whereas the CMV PCR on blood was negative. A CMV PCR was also performed on the frozen CSF sample, collected at day +178. The viral load in this sample was also very high (6.8 x 105 copies mm-3). To detect why the clinical and radiological pictures were so different between the two episodes, despite the similar CSF viral loads in both specimens, CSF inflammatory cytokines concentrations were measured. IL-6 value was very high (96.07 pg mL) only in the CSF sample collected during the onset of neurological symptoms, suggesting a robust immune restoration and a likely CMV-induced IRIS.
The girl was started on a combined dual antiviral therapy with ganciclovir (10 mg kg-1 day-1), foscarnet (1800 mg kg-1 day-1) and weekly CMV-hyperimmune globulin (Cytotect CP, Biotest, Germany) infusions (200 U kg-1 dose-1). All the neurological symptoms began to improve right away. Unfortunately, the CSF viral load did not drop significantly after two, four and eight weeks of dual therapy. The possibility of a drug-resistant CMV strain was ruled out by the genotypic resistance test, which was aimed at detecting specific mutations in UL97 and UL54 genes.
At day +266, after two months of dual antiviral therapy, the girl developed severe renal impairment, neutropenia and thrombocytopenia. The CSF viral load was still very high, despite the complete clinical and radiological recovery. To avoid further renal and bone marrow toxicity, the dual antiviral therapy was suspended and Cytotect CP treatment alone was continued, at an increased frequency of 200 U kg-1 dose-1 for five consecutive days every week. At day +287, the CSF viral load dropped to 900 copies mm-3 and was undetectable at day +308. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery. On discharge, the girl was in excellent clinical condition, and she continued the CMV-hyperimmune globulin prophylaxis once a week for two months as an outpatient. Five years out of HSCT, the girl remains in perfect health and has not experienced any further CMV reactivations. All data regarding blood and CSF viral loads are displayed in Table 1.
During the Cytotect CP treatment, we measured the CMV-IgG antibody levels in the blood and CSF of our patient. The CNS antibody levels were significantly higher than those in blood in all the tests. For comparison, we conducted a retrospective analysis based on plasma and CSF samples stored in our biobank. From our records, we identified 30 CMV-IgG-positive paediatric patients affected by haematologic malignancies who had undergone standard treatment protocols and for whom both plasma and CSF samples were stored. None of these patients had CMV-related CNS involvement. All samples were obtained 3-5 months post-transplant. A minimum of three peripheral blood samples were collected for each patient. Except for the patient featured in this paper, there was only a single CSF sample for each of the patients. We divided selected patients into two comparable groups of 15 each. The patients in the first group had received prophylactic treatment with Cytotect CP (Cytotect group), while those in the second group had not (Control group). We performed serum and CSF CMV-IgG antibodies titre evaluation on the frozen samples. Comparing the titres of CMV-IgG antibody in blood and CSF, we found a statistically significant correlation in antibody concentration within each group, with an inverse correlation in the Cytotect group (P < 0.001 for the Cytotect group, P < 0.0001 for Control group). Comparing the titres of CMV-IgG antibody in blood and CSF across both groups, a positive correlation was found in blood antibody concentration, while CSF antibody concentration showed an inverse correlation (P < 0.0001 for both). Comparing the CMV-IgG antibodies blood/CSF ratio, we found statistically significant differences in antibody concentrations between the two groups, with inverse correlation in the Cytotect group (P < 0.001 for Cytotect group, P < 0.0001 for Control group). Similarly, comparing blood and CSF CMV-IgG titres in both groups, the positive correlation was found in blood antibodies concentration, while CSF antibodies titre showed an inverse correlation (P < 0.0001 for both). The results are shown in Figure 2. | cmv‐hyperimmune globulin, il‐6, cerebrospinal fluid cmv antibodies, cytomegalovirus (cmv)‐related encephalitis, immune reconstitution inflammatory syndrome (iris) | Not supported with pagination yet | null |
PMC5992291_01 | Male | 62 | A 62-year-old man was admitted to the Emergency Department for dyspnea and chest pain. His medical record was notable for unilateral renal agenesis. He worked as a clerk and did not smoke, drink alcohol, or use illicit drugs. He had neither a family nor a personal history of cancer or autoimmune diseases; however, he reported having been hospitalized twice during the previous year for recurrent pericardial effusions, for which he had been diagnosed with IRP and was receiving treatment with colchicine and NSAIDs.
On examination, blood pressure was 120/60 mmHg, heart rate 96 beats per minute, and respiratory rate 30 breaths per minute, with normal oxygen saturation. Physical examination revealed muffled heart sounds, but no jugular vein distention or paradox pulse. Blood tests revealed mild anemia, mildly elevated troponin levels (43 ng/L, normal values < 14), elevated levels of pro-BNP (3,600 pg/mL, normal values < 227), and strikingly high levels of inflammatory markers C-reactive protein (CRP, 135 mg/L, normal values < 6), erythrocyte sedimentation rate (ESR, 118 mm/1 h, normal values < 20), and ferritin (640 ng/mL, normal values 15-150 ng/mL). A full autoantibody panel, including rheumatoid factor, anti-citrullinated protein antibody, antinuclear antibodies, cryoglobulins, and anti-neutrophil cytoplasmic antibodies, was negative. Electrocardiogram showed diffuse ST-segment elevation. Trans-thoracic echocardiography revealed ubiquitous pericardial effusion, with a maximum thickness of 45 mm. Following ineffective attempts to drain the excess pericardial fluid, a pleuro-pericardial window was surgically created. Pericardial fluid analysis revealed elevated concentrations of lactate dehydrogenase and total protein. A search for cancer cells and Mycobacterium tuberculosis through polymerase chain reaction was negative, as were Gram stain and bacterial culture studies.
Over the following days of hospitalization, dyspnea and chest pain progressively worsened. Repeated echocardiography revealed a closure of the pleuro-pericardial window and relapse of the pericardial effusion, with a maximum thickness of 40 mm. A whole-body contrast-enhanced computed tomography (CT) confirmed pericardial effusion with thickening of the pericardial sheets, while also revealing a pseudo-tumoral infiltration of the right atrium (Figure 1). Moreover, abdominal scans revealed solid tissue surrounding the right kidney and aorta (Figure 2). Together with cardiac involvement, these findings of retroperitoneal involvement with peculiar "coated aorta" and "hairy kidney" radiologic signs pointed at a diagnosis of ECD. Since the skeletal system is almost invariably involved in ECD, a bone scan was then requested, which revealed pathognomonic symmetric radiotracer uptake in the long bones of the lower limbs (Figure 3). A CT-guided biopsy of the perinephric solid tissue was performed. Histology studies identified xanthogranulomatous infiltration with foamy histiocytes staining positive for CD68, but negative for S100 and for CD1a, all findings diagnostic for ECD. Molecular techniques revealed the presence of the BRAFV600E mutation in pathological histiocytes, as described.
Once a diagnosis of ECD was established, a critical problem to be faced was which pharmacological approach to choose following failure of the pleuro-pericardial window. The traditional drug of choice in ECD is IFN-alpha. However, we preferred not to choose IFN-alpha, as previous experience suggests limited efficacy in cases of severe heart inflammation. As a valid alternative, we focused on vemurafenib, a small molecule inhibitor of BRAFV600E, which is highly effective in the treatment of ECD. However, efficacy of vemurafenib is normally observed only after months of treatment, while the pericardial effusion of our patient was quickly worsening and dictating the need for a rapid intervention. The last alternative therapeutic strategy involved the use of anti-cytokine agents. The main anti-cytokine therapies that have been investigated in ECD are (1) anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, (2) infliximab, a TNF-alpha monoclonal chimeric antibody, and (3) tocilizumab, a monoclonal antibody blocking the IL-6 receptor. Between these three drugs we chose anakinra, because of its rapid onset of action, excellent safety profile, and:above all:the demonstrated efficacy in the treatment of idiopathic pericarditis, as well as ECD.
Anakinra was thereby started at a standard daily subcutaneous dose of 100 mg. Already 2 days after initiation of anakinra treatment, laboratory tests showed a steep reduction of ESR and CRP levels (22 mm/1 h and 16 mg/L, respectively), and the patient reported a marked improvement of fatigue and asthenia. In the following days, repeated echocardiography evaluations revealed progressive reabsorption of the pericardial effusion. The patient was thereby discharged and re-evaluated after 2 months of daily anakinra treatment. At this point, inflammatory markers had completely normalized, hemoglobin levels increased, and the patient reported no signs of cardiac failure and a considerable improvement in quality of life. A new echocardiography showed a substantial reduction of pericardial effusion, which had a maximum thickness of 16 mm. Anakinra was maintained as monotherapy, and the patient remained asymptomatic in the absence of disease flares for the following 1 year. Imaging restaging of ECD confirmed improvement of heart involvement and stability of retroperitoneal fibrosis. | erdheim–chester disease, anakinra, cytokines, inflammation, interleukin-1, pericarditis | Not supported with pagination yet | null |
PMC10062096_01 | Male | 25 | A 25-year-old young man who was a cleaner by occupation coming from a low middle-class family attended at outpatient department of chittagong eye infirmary and training complex Institute with a history of sudden painless vision loss in his left eye for 20 days. He did not give any significant past medical history. He was a smoker who used to take 1 pack per day. He was neither a drug user nor had any history of alcohol intake. At first, he denied any sexual exposure but eventually agreed.
On examination, visual acuity of the right eye was 6/6 and the left was 6/60. Both pupils were round and regular. Direct and consensual reactions of both eyes were normal. The left pupil showed a relative afferent pupillary defect. Color vision by Ishihara test on the right eye, he read all plates but on the left eye, he could identify only two plates. The anterior segment of both eyes was found normal. The posterior segment showed a hyperemic left optic disc, margin blurred, swollen, and nerve fiber layer edema [Figure 1a and b]. Fluorescence angiography showed hyperfluorescence of the left optic disc indicating edema, and the rest of the retina of both eyes was within normal limits [Figure 2]. Routine blood tests, urine tests, random blood sugar, and magnetic resonance imaging (MRI) of the brain were within normal limits. He was diagnosed with optic neuritis in the left eye and injectable corticosteroid was given for 3 days followed by oral corticosteroids as per the schedule of optic neuritis. His vision was gradually improving within 1 month and became 6/9 on his left eye. However, after a month, the patient returned with a blurring of vision in the same eye for 3 days. An extensive blood test was done including the Monteux test, C-reactive protein, venereal disease research laboratory (VDRL) test, T. pallidum hemagglutination assay (TPHA), and HIV serology. Notably, we also performed serum autoimmune antibody neuromyelitis optica immunoglobulin-G (NMO-IgG)/antibody to aquaporin-4 to exclude NMO, which was found negative. No abnormality was detected in all other blood tests except VDRL and TPHA in blood were found positive. TPHA had a high titer (1:1280 dilutions) and rapid plasma reagin (RPR) titer (1:64 dilutions) was also high. The patient then admitted having had a history of unprotected commercial sex 1 year ago, after which he had a single, painless ulcerated penile lesion healed without any antibiotic treatment. He did not notice any later symptoms attributable to secondary syphilis. We also examined but did not find any local genital skin lesions. Then, he was advised to do a cerebrospinal fluid (CSF) study. The CSF analysis showed leukocytosis (80 cu/mm lymphocyte), and VDRL and TPHA were found positive with TPHA titer found 1: 80 dilutions. RPR was also reactive. The biochemistry examination of CSF showed glucose 55 g/dl and protein 45 g/dl. No bacteria were found including tuberculosis. Adenosine di aminase was also negative (<5 U/L). Based on these clinical and laboratory examinations, he has been diagnosed with a case of neurosyphilis with optic neuritis.
The ideal treatment of neurosyphilis is intravenous (IV) injection of 3-4 million units of aqueous crystalline penicillin at every 4 h for 10-14 days or intramuscular injection of 2.4 million units penicillin G procaine daily along with oral 500 mg probenecid four times daily for 10-14 days. However, penicillin formulations are not currently available in our country. Therefore, as an alternative treatment, IV 2 g ceftriaxone had been given for 14 days. The systemic steroid was also administered under the coverage of antibiotics. The patient's visual acuity was improved within 1 month. On the left eye, it was 6/9, could read five plates of Ishihara chart and the optic disc showed mild edema, which are the signs of improvement. He was advised to repeat VDRL, TPHA, and CSF study after 3 months. | cerebrospinal fluid analysis, injectable ceftriaxone, neurosyphilis, optic neuritis | Not supported with pagination yet | null |
PMC4005207_01 | Male | 48 | A 48-year-old married male, tobacco user presented with darkening of skin of the right leg and appearance of red colored spots on his abdomen since last 1 week. There was no history of fever, joint pains and bluish discoloration of fingers or bleeding from any site. He was diagnosed as a case of tuberculosis of the ankle joint 3 weeks before presenting to us and started taking anti-tubercular therapy since then. Examination of the right leg showed blackening of skin overlying anterior aspect of the tibia and foot [Figure 1]. There were hyperkeratotic purpuric eruptions on the left leg [Figure 2] and red macular lesions of varying size over the lower part of abdomen [Figure 3]. There was mild tenderness over the right leg and dorsalis pedis artery was palpable in both limbs. Systemic examination was normal. A provisional diagnosis of cellulitis with vasculitis was made and skin biopsy was planned. His other significant investigations were the thin-layer chromatography-11,600/cu mm, erythrocyte sedimentation rate 29 mm/1st h, perinuclear anti cytoplasmic antibody pANCA and anti-saccharomyces cerevisiae antibodies negative, rheumatoid factor: <8 IU/mL. Patient was started with amoxicillin and clavulanic acid along with anti-inflammatory drugs. However, his condition did not change. Skin biopsy reported negative for any changes of vasculitis. Suspecting it as the case of drug reaction we stopped anti-tubercular drugs isoniazid, rifampicin, pyrazinamide and ethambutol, which the patient was taking in a fixed dose regime. After 2 days, the eruptions over abdomen disappeared. The skin changes over legs did not progress any further. | antitubercular therapy, cutaneous drug reactions, vasculitis | Not supported with pagination yet | null |
PMC8107658_01 | Male | 54 | A 54-year-old man originally presented to his primary care physician in January 2019 complaining of two painful swellings in the arch of his left foot. An ultrasound scan (USS) examination was requested. Two well-defined hypoechoic lesions arising from the distal portion of the left plantar fascia were described. The distal lesion measured 13.5 mm in length x 5.2 mm in width (Figure 1) the proximal lesion measured 7.9 mm x 2.8 mm (Figure 2). No significant intra-substance vascularity was seen. The remaining plantar fascia was normal. Appearances were in keeping with LD.
The patient had a history of nicotine use (15-20 cigarettes a day), essential hypertension and chronic lumbar region pain. He had stable epilepsy and was recovering from alcohol abuse. His current medication was lisinopril 20 mg od, gabapentin 400 mg tds, codeine/paracetamol 30/500 mg combination prn and sodium valproate 500 mg tds. The patient had concomitant palmar Dupuytren's disease on the left hand with fascial nodules and contracture of the fourth finger. There were no known allergies and no relevant family or surgical history.
Following the results of the USS organised in primary care, he was seen by our service in February 2019 complaining of searing pain on the medial longitudinal arch of the left foot of 6 months duration. He described the pain as severe and debilitating and rated his discomfort at 9/10 on a visual analogue scale (VAS). On examination he had two firm, sub-epidermal swellings in the distal-medial aspect of the arch associated with the central slip of the plantar fascia. Normal neurovascular status was observed. His symptoms had worsened over the previous 3 months, aggravated by activity and weightbearing. Prior treatment included accommodative footwear and orthoses. Intralesional CSI in combination with a fenestration/needling was recommended and informed, written consent was obtained, backed up with a patient information leaflet. Written permission to use images for publication was obtained.
One week following initial consultation, the patient attended for their planned procedure. As the patient presented with significant pain, the procedure was performed under tibial nerve block, performed at the level of the ankle with 3 mL of 0.75% ropivacaine under aseptic technique. The injection sites were prepared with a chlorhexidine gluconate 2%/isopropyl alcohol 70% mix. A sterile cover was placed on the ultrasound probe and sterile coupling gel utilised. The ultrasound probe was placed plantarly and longitudinal to the lesion to allow for a medial injection approach. A mixture of 20 mg (40 mg/mL) triamcinolone acetonide and 1 mL of mepivacaine hydrochloride was deposited with intralesional fenestration (20-30 repeated passes with multiple micro-deposition sites from proximal to distal and medial to lateral without removing the needle from the skin) initially to the distal lesion followed by an identical preparation administered to the proximal lesion. The whole of the fibroma is targeted but avoiding being too superficial (skin atrophy), or too deep (reduced effectiveness). A sudden loss of resistance during the injection indicates that the lesion has been penetrated too deeply or adjacent to the lesion.
Both injections were performed under ultrasound guidance with confirmation of intralesional deposition. An extremely small amount of perilesional injectate leakage was noted. Importantly, a 2.5-mL Luer lock syringe with a 23 gauge/25 mm needle was utilised as experience has shown the presence of pressure when injecting a solid mass which can cause de-coupling of the syringe from needle. No significant bleeding was associated with the procedure. A simple self-adhesive dressing was applied to the injection sites. Post procedure advice included rest and foot elevation for the remaining day. The patient could return to daily living activities the following day but was to refrain from impact activity, for example, sports until follow-up at 6 weeks post procedure. As well as the usual post-injection advice, particular reference to the small risk of fascial rupture was made.
No significant beneficial effect was witnessed at the 6-week review, as such, a second injection was recommended. Eight weeks following the original procedure, the same protocol as described above was undertaken. In this instance, palpation-guided injection and fenestration was undertaken (Figure 3). Six weeks post the second procedure (total 14 weeks post index procedure), a significant reduction in the size and rigidity of both lesions was reported clinically. A repeated VAS was 2/10.
For purposes of audit, the patient was reviewed at 12 months post procedure and a further USS examination was undertaken showing a significant regression of both nodules: the distal nodule to 6 mm x 1.9 mm (Figure 4) and the proximal nodule to 2.4 mm x 1.2 mm (Figure 5). During this period, the patient had no regression of symptoms. A VAS completed at 12 months was 0/10. Clinically, the proximal nodule was no longer palpable or visible, the distal nodule remained palpable but not visible. No pain was felt on palpation. The patient remarked they were unable to feel any nodule on ambulation. No adverse signs or symptoms were reported. | ledderhose disease, corticosteroid injection, fenestration, needling, peppering, plantar fibromatosis, triamcinolone | Not supported with pagination yet | null |
PMC8107658_02 | Female | 55 | A 55-year-old woman attended our service in August 2018 complaining of bilateral plantar nodules; at initial presentation only the right foot was symptomatic. The patient's medical history included type 2 diabetes mellitus of 12 years duration (recent HbA1c 52 mmol/mol) and essential hypertension. Current medication was empagliflozin 10 mg od, linagliptin 5 mg od, gliclazide 80 mg bd, ramipril 10 mg od, atenolol 50 mg od and amlodipine 15 mg nocte. There were no known allergies and no relevant family/social or surgical history.
When assessed the patient described a 12-month history of a symptomatic mass within the medial longitudinal arch of the left foot, a VAS of 8/10. Symptoms were exacerbated by prolonged periods of ambulation and weightbearing. Orthoses and footwear adaptation had not yielded any symptomatic reprieve. Clinically, a solitary mass could be palpated within the medial longitudinal arch of the right foot, and tenderness was apparent on palpation. The mass was rigid, overlying tissue unremarkable. Neurovascular observations were unremarkable. Subsequently, an USS examination was requested (Figure 6). The proximal plantar fascia appeared normal; however, a large solitary well-defined hypoechoic mass was seen within the medial band of the plantar fascia measuring 24.1 mm in length and 7 mm in width. Appearances again were consistent with LD. As conservative treatment options had failed so far, a CSI was suggested. Informed written consent was obtained, backed up with a patient information leaflet. Written permission to use images for publication was obtained.
In September 2018, the patient underwent a single injection, without fenestration, of 40 mg (40 mg/mL) methylprednisolone acetonide pre-mixed with lidocaine (10 mg/mL) under USS guidance. While moderate improvement was seen at 6 weeks post procedure, the patient returned 3 months following the injection noting complete recurrence of symptoms. The patient was subsequently listed for the triamcinolone acetate injection with fenestration under USS guidance. This was performed in March 2019: the injection technique mirrored that described in case study 1. At 6 months post final procedure, the patient reported VAS as 1/10 and return to full activities.
For audit purposes, the patient was contacted for review at 12 months post procedure and USS examination performed in March 2020. The VAS was 0/10; clinically the mass was significantly smaller with only minimal deciphering on manual palpation. The USS demonstrated a small hypoechoic mass sited in the same area as previously demonstrated but with reduced dimensions, as seen in Figure 7 (note: as this coincided with the start of the Covid-19 pandemic, the lesion was scanned by ourselves rather than by the local sonography team who were only taking emergency cases at that time, and therefore no definitive dimensions are offered). No adverse signs or symptoms were noted and no further treatment of any sort had been required. | ledderhose disease, corticosteroid injection, fenestration, needling, peppering, plantar fibromatosis, triamcinolone | Not supported with pagination yet | null |
PMC9674503_01 | Female | 33 | A 33-year-old woman was admitted to the emergency department due to acute onset of abdominal pain in the right side without any reported trauma or other apparent causes.
The US abdominal examination revealed the presence of two masses: one at the right kidney, and the other one at the right lobe of the liver.
A contrast-enhanced computed tomography was then acquired and confirmed the two lesions. The one on the right kidney (Fig. 1) measured 7 cm and showed intense arterial enhancement. The lesion on the VI-VII hepatic segments (Fig. 2) measured 5 cm and showed arterial enhancement with wash-out in portal phase.
Also, an enhanced magnetic resonance imaging (MRI) study of the upper abdomen with hepato-specific contrast agent was performed and showed the same angio dynamic behavior of the lesions, which also had high signal intensity in DWI with high b-value (800) (Fig. 3).
The physical examination was completely silent. In anamnestic history, the patient reported psoriasis, previously treated, a mild smoke habit lasted for about 15 years, no alcohol abuse and a varied diet. At the time of symptoms presentation, no drug therapy was mentioned.
About family oncological history, the patient reported a bladder cancer in the paternal grandfather and a prostate cancer in the father.
At the admission, the serum biochemistry analysis was all in the normal range, except for CA125 and AFP a little over the norm, as follows: CEA 1.2 ng/ml (normal range, 0-5), CA 19-9 7.4 U/ml (normal range 0-37), CA 125 42.3 U/ml (normal range, 0-35), CA 15-3 19.5 U/ml (normal range, 0-23.5), AFP 13.4 ng/ml (normal range < 10).
After CT finding, further investigations were required for staging purposes: head and chest CT enhanced scan, bone scintigraphy, and liver and kidney biopsy for a definitive diagnosis.
The CT scan reported multiple areas of thickening with a tendency for peri-bronchial distribution to both lung fields; no lymphadenopathies, no brain lesions (Fig. 4). Bone scintigraphy was negative.
Liver and kidney biopsies revealed the presence of 2 primary synchronous malignancies: high grade HCC (G3, Edmondson classify.) (Fig. 5) and clear cell renal carcinoma (nucleolar grade 3, WHO classify) (Fig. 6).
To characterize the lung lesions, the patient underwent to a wedge resection through video-assisted thoracoscopic surgery. Subsequent histological analysis showed that the lung lesions were not secondary nodules, as suspected, but sarcoidosis granulomas.
Genetic surveys were also carried out to identify a genetic syndrome that could explain the presence of a double neoplasm in young patient without familiar predisposition and in the absence of hepatopathy. However, no specific genetic syndrome was detected.
The patient was referred to surgeons for surgical treatment of the 2 neoplasms. During the surgery, she underwent an intraoperative hepatic contrast-enhanced ultrasound that depicted additional nodules at the II, III, and VIII hepatic segments of doubtful nature. Thus, she underwent a resection of HCC at VI and VII segments and an additional wedge resection of the above segments plus right nephrectomy. The histological analysis revealed that the lesion at the III segment was focal nodular hyperplasia, whereas the nodules at II and VIII segments turned out to be sarcoidosis granulomas.
The histopathologic stage of renal cancer was pT2a Nx Mx (G3) (AJCC 8th 2016).
The postoperative course was uneventful, and the patient was discharged on day 9 post-surgery. Approximately 1 year after surgery, a follow-up CT scan shows the appearance of some solid nodular formations at the right lung, characterized by radiopharmaceutical uptake at the PET-CT scan as suspicious for secondary pulmonary nodules.
The patient underwent a wedge resection through video-assisted thoracoscopic surgery for nodule exheresis and the histological examination confirmed their secondary nature from HCC. The postoperative course was characterized by the appearance of PNX that resolved in the following days by drainage.
The patient started systemic therapy with Lenvatinib. Four months later, on follow-up CT scan, there was evidence of suspicious mediastinal lymphadenopathy. The patient underwent endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA).
Histological examination was diagnostic of lymph node metastasis from high-grade HCC.
Due to disease progression, the systemic therapy was switched to second line Sorafenib and then to Cabozantinib as third line.
To date, the patient is still being followed up and the disease is stable.
In addition to systemic therapy, the patient starts Prednisone for sarcoidosis, Amlodipine for hypertension, and Levothyroxine for hypothyroidism. | hepatocellular carcinoma, renal cell carcinoma, sarcoidosis, synchronous, young | Not supported with pagination yet | null |
PMC5505920_01 | Female | 19 | A 19-year-old Japanese woman was admitted to a local community hospital (day 1) with a 6-day history of a fever, chills, dyspnea, and general malaise. Chest computed tomography (CT) obtained at the hospital showed diffuse ground-glass opacity in both lungs and multiple mediastinal lymphadenopathy (Fig. 1), and empiric antibiotic therapy (SBT/ABPC, MINO) was started. She underwent a transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL) on day 4 that disclosed noncaseating epithelioid granuloma without any organisms. Acid-fast staining of the sputum (three sets) and bronchoalveolar lavage fluid (BALF) also showed negative results. After a bronchoscopic examination, she developed respiratory failure, and steroid pulse therapy was started (day 4). After the steroid pulse therapy, her breathing state and pulmonary abnormal findings on computed tomography (CT) improved (day 9). However, on day 13, the high fever recurred during steroid reduction, and her multiple mediastinal lymphadenopathy persisted. In addition, her plasma soluble interleukin-2 receptor (sIL-2R) level was elevated (2,587 pg/mL). Therefore, the previous doctor suspected malignant lymphoma, and she was referred to our hospital for a definitive diagnosis.
On admission to our hospital (day 15), she presented with a fever and general malaise. She did not smoke or consume alcohol or travel, and she had no remarkable medical history. Her grandfather had a history of tuberculosis three years prior, and she occasionally interacted with him. Her body temperature was 40 C, heart rate 90 beats/min, blood pressure 109/62 mmHg, respiratory rate 18 breaths/min, and oxygen saturation 93% under normal conditions. On a physical examination, the edge of the liver could be felt 2-3 cm below the right costal margin without splenomegaly or lymphadenopathy. There were no rales on chest auscultation, and a cardiac examination revealed a regular rate and rhythm with no murmurs. Chest X-ray and CT obtained on admission revealed consolidation in the left upper lung field, ground-glass opacity in both lungs, and multiple mediastinal lymphadenopathy (Fig. 2). Abdominal ultrasound showed hepatosplenomegaly with coursing echogenicity of the liver. Laboratory work-up revealed decreased levels of hemoglobin and elevated levels of AST, ALT, ALP, gamma-GTP, LDH, CRP, TG, fibrinogen, FDP, D-dimer, ferritinm, sIL-2R, and ACE (Table 1). A peripheral blood smear showed monocytosis with hemophagocytosis. Further evaluations, including (1,3)beta-D-glucan, legionella, mycoplasma, chlamydia, cytomegalovirus, Epstein-Barr virus antigen titers, and HIV ELISA, were all negative. The result of QuantiFERON-TB 3Gold (QFT-3G) was indeterminate. Several sets of blood cultures were negative, and sputum culture disclosed only yeast-like microorganisms.
On day 22, pancytopenia developed (white blood count cell count of 2,320x103/muL, hemoglobin 7.3 g/dL, platelet count 8.0x104/muL), and these results and clinical course suggested potential diagnoses of HPS, malignant lymphoma, sarcoidosis, hypersensitivity pneumonia, and tuberculosis. Therefore, we performed a bone marrow biopsy and TBLB again (day 23). The biopsy showed hemophagocytosis and noncaseating granulomatous inflammation without evidence of acid-fast bacilli or lymphoma. TBLB also disclosed noncaseating epithelioid granulomatous inflammation without evidence of acid-fast bacilli (Fig. 3). After a bronchoscopic examination, she developed respiratory failure, and steroid pulse therapy (intravenous methylprednisolone 1,000 mg/body for three days) was started on the same day. Both acid-fast staining and tuberculosis-polymerase chain reaction (PCR) testing of the BALF showed negative results. On day 24, we learned that the BALF culture obtained at the previous hospital had grown Mycobacterium tuberculosis. The patient then underwent tuberculosis-PCR testing of the urine, and the result was positive. Our patient now met five of the eight criteria for HPS. Therefore, a diagnosis of tuberculosis associated with HPS was given.
Antituberculous therapy (isoniazid 5 mg/kg/day, rifampicin 10 mg/kg/day, ethambutol 15 mg/kg/day, and pyrazinamide 20 mg/kg/day) was started on day 24. She responded well to the treatment, and her fever and respiratory failure improved on day 31. In addition, her hematological abnormalities resolved, and her radiological abnormalities improved on day 38. Four weeks later, it was revealed that the sputum culture obtained on admission at our hospital had also grown M. tuberculosis. The patient has been in a stable condition without any recurrence during or after treatment for two years. | hemophagocytic syndrome, miliary tuberculosis, noncaseating epithelioid granulomatous inflammation | Not supported with pagination yet | null |
PMC9888409_01 | Female | 5 | The proband was a five-year-old female patient (deceased). The proband (II-1) had the clinical features such as chondrodysplasia, short stature, and global developmental delay (Figure 1A).
The midline structures, including the pituitary gland and suprasellar regions, were normal. The foramen magnum is unremarkable. There was no evidence of basilar invagination. The base of the skull angle measures 179 , suggestive of platybasia. The gray/white matter differentiation was preserved. There was delayed myelination for the patient's age. No definite cortical deformity was identified. Posterior fossa structures were normal with no evidence of Chiari 1 malformation. Prominent and extra-axial CSF spaces with prominent ventricular consistency were observed at infancy. There was no hydrocephalus, hemorrhage, or space-occupying lesion. Posterior fossa structures were normal with no Chiari I change. The visualized parts of the orbit, paranasal sinuses, and labyrinthine structures were normal. There was occurrence of platybasia at the skull base, and delayed myelination for the patient's age was observed (Figure 1B).
The right kidney measures 6.7 cm (previously 6.5 cm), and the left kidney measures 7 cm (previously 6 cm). Both kidneys demonstrated normal parenchymal echogenicity and good corticomedullary differentiation with multiple non-obstructed stones. Persistent bilateral non-obstructing renal stones were more on the right side. Grade 1 right hydronephrosis was observed, along with urinary bladder debris correlating with urinalysis laboratory values.
The enteric feeding tube was placed in the proper position within the stomach. A double stoma was observed in the left upper quadrant. The afferent and efferent loops were observed to be collapsed. The contrast was observed in the efferent loop opacifying the sigmoid colon. The significant proximal jejunum, duodenum, and gastric dilatation were related to high-grade mechanical bowel obstruction. The distal bowel loops were collapsed. The maximal diameter of the small bowel that courses behind the mesentery into the left abdomen was 3.1 cm. However, it was difficult to assess the proximal continuity of the bowel loop. This could be related to an internal hernia. The pelvis had minimal free fluid and several non-obstructive right renal stones. The largest stone recorded was of size .8 cm. The visualized chest parts showed bilateral subsegmental atelectasis/consolidation in the lower lobes. The liver, spleen, pancreas, and adrenals were unremarkable (Figures 1B-E).
The affected individual manifested widened irregular metaphysis with more destructive changes at the proximal femoral ends. In addition, there was a bilateral superolateral displacement of the proximal femur and stippled calcification along the knee joints. Levoscoliosis in the thoracolumbar spine and symmetrical limb shortening were observed. All these skeletal changes favor the chondrodysplasia punctata type of skeletal dysplasia (Figures 1B-E).
DNA of the affected member (II-1) was subjected to WES using standard methods. The variant filtration criteria were based on the gnomAD frequency of <=.0001, CADD-Phred score of >=15, exonic and splice site (+/- 12 bp) variants, and Kaviar allele count of <=10. A de novo nonsense variation in the TBX2 gene (c.529A>T; p.Lys177*; NM_005994.4) was detected which was validated by Sanger sequencing (Figures 1F, G). The variant had a CADD-Phred score of 39 and a GERP++ score of 4.81. Combined Annotation-Dependent Depletion (CADD) and other associated tools are widely used to measure the disease-causing nature of variants that can effectively prioritize causal variants in genetic analyses. These tools are integrative annotation built from several genomic features and can score human single-nucleotide variants and short insertion and deletions effectively. The Lys amino acid at position 177 was highly conserved across different species (Figures 1H, I). According to ACMG, the identified variant was classified as likely pathogenic (Class 2).
Structural analysis of TBX2WT and TBX2LYS177TER revealed several differences between the two proteins. Specifically, in TBX2LYS177TER, the alpha2 and alpha3 regions were fused together to form a single alpha2 region, while the alpha7 region was converted into a loop. Additionally, the loop between alpha7 and alpha8 was converted into a helix (designated alpha8 in TBX2LYS177TER), and the alpha11 region was extended from Lys166 to Ala175 (Figures 1J, K). These structural changes were unique to TBX2LYS177TER and were not present in TBX2WT.
The root mean square deviation (RMSD) is a measure of the stability of a protein structure over time. In this study, the observed RMSD values of 8-12 A for TBX2WT and 10-15 A for TBX2LYS177TER suggest that both systems displayed relatively stable behaviors during the simulation. However, the higher RMSD values for TBX2LYS177TER may indicate that this protein is less stable than TBX2WT. This difference in stability may be due to structural differences between the two proteins, such as the fusion of the alpha2 and alpha3 regions and the conversion of the alpha7 region into a loop in TBX2LYS177TER, which may introduce additional conformational flexibility into the protein. The analysis of fluctuating amino acids also indicates that TBX2LYS177TER is less stable than TBX2WT, as TBX2LYS177TER exhibits increased fluctuation in certain amino acids, including Pro21, Asp23, Ala63, Ala65, Lys112, Trp115, Phe118, Lys148, and Arg164. These structural changes, such as the extension of the alpha11 region and the formation of a new helical region (alpha8) in TBX2LYS177TER, may also contribute to the increased fluctuation in certain amino acids. Additionally, the radius of gyration, which is a measure of the compactness of a protein structure, indicates that TBX2WT has a more compact structure than TBX2LYS177TER. The observed radius of gyration values of 33-35 A for TBX2WT and 25-30 A for TBX2LYS177TER suggest that TBX2WT has a more tightly packed structure. This difference in the packing density may also contribute to the overall stability of the proteins, as a more compact structure may be less prone to conformational changes. In summary, the observed differences in RMSD values, fluctuation in amino acids, and radius of gyration values suggest that TBX2LYS177TER is less stable than TBX2WT. At the 0 ns time scale, both TBX2WT and its mutant form are in open conformations. However, upon reaching the 100 ns time scale, both proteins exhibit a shift toward close conformations. This change is likely due to the close contact between the N- and C-terminals over the course of the simulation. As a result of this interaction, TBX2WT assumes a circular shape, with the inner side forming a circular cavity (as depicted in Figures 2G, H). It is worth noting that the shift from open to close conformations may have different functional consequences for the wild-type and mutant forms of TBX2. Further investigation is necessary to fully understand the impact of these conformational changes on the function of these proteins. | tbx2, wes, chondrodysplasia, nonsense mutation, novel variant | Not supported with pagination yet | null |
PMC4018290_01 | Unknown | 15 | Of the 8.6 million people diagnosed with tuberculosis (TB) disease in 2012, an estimated 530, 000 (6%) were children under 15 years old. The actual percentage of TB occurring in children is likely as high as 11-15%, given the lower case ascertainment rates in children compared with adults. The impact of TB is particularly profound in young children because they progress more rapidly to TB disease and are more susceptible to severe TB. Viet Nam, one of 22 high burden countries that collectively account for about 80% of the world's TB cases, has an estimated TB disease incidence of 147 cases per 100,000, with an estimated prevalence of TB infection (as measured by Tuberculin Skin Test (TST) >= 10 mm) of 16.7% among 6-14 year-olds. Despite the suspected high burden of TB disease among children in Viet Nam, there have been few childhood TB studies in this region, and the clinical manifestations and treatment outcomes of childhood TB in Viet Nam remain unclear. Bacteriologic confirmation of childhood TB is low, necessitating a heavy reliance on clinical characteristics to direct diagnosis and treatment in the majority of cases. As such, a better understanding of the complex and heterogeneous clinical manifestations of childhood TB is necessary for developing and implementing more effective TB prevention, diagnostic, and treatment strategies. To address this need, we conducted a case series study at a large referral hospital in Northern Viet Nam to better characterize the demographics, clinical presentation, radiographic and microbiologic findings, treatment, and clinical outcomes of children diagnosed with TB disease in Northern Viet Nam. | null | Not supported with pagination yet | null |
PMC3195365_01 | Female | 47 | A 47-year-old woman was admitted to the Nagoya City University Hospital, Nagoya, Japan, complaining of an abdominal swelling that had been present for the past 12 months. Her abdomen was markedly swollen and felt hard without tenderness. Peripheral blood examination revealed slight anemia and slight elevation of C-reactive protein. No other disorders, including any tumor markers, were detected. A computed tomography scan (CT) showed two masses in the retroperitoneum, one of which was 26 x 15 x 29 cm and enhanced slightly, and the right kidney was involved and pushed aside. Almost all retroperitoneal cavities were filled with the giant tumor. The other mass was walnut-sized tumor adjacent to the large one, and mostly of low density. Magnetic resonance imaging (MRI) revealed the giant tumor was T1-low intensity and T2-high intensity, but the small tumor was T1-high intensity, with a changed low signal in fat suppression (Figure 1). This indicated that the small tumor was mainly fat-containing, and the giant tumor appeared to be mainly composed of mucinous tissue. Under general anesthesia, the tumor was excised with the right kidney en bloc. There was not much adhesion to surrounding tissues. Upon gross examination, the tumor was well circumscribed and encapsulated and weighed 8.5 kg (Figure 2). The tumor had two components as determined by CT and MRI. The two components were very clearly divided. The small one was yellowish, and histopathologically, they were mainly composed of fat cells that varied in size, that is, mature-appearing adipose tissue with scattered lipoblasts exhibiting large hyperchromatic nuclei. Immunohistochemical analysis revealed that the cells were strongly stained by S-100 protein which is a marker for fat (Figure 3). Therefore, this small tumor was diagnosed as a well-differentiated liposarcoma. On the other hand, giant tumor was white and, histopathologically, mainly contained abundant mucinous mesenchyme and filled with atypical spindle cells. There was extensive in-depth invasion into the renal parenchyma, but the surgical margin was negative. According to immunohistochemical analysis, the poorly differentiated tumor cells had no expression of several mesenchymal markers containing S-100 protein. Therefore, a comorbid malignant fibrous histiocytoma (MFH), or other myxoid tumor could not be ruled out. Consequently, we focused attention on FISH analysis, using specific probes for the MDM2 gene (Figure 3). The amplification of MDM2 gene was detected in the nuclei of both small and giant tumors. Thus, a definitive diagnosis was made of the two tumors as a dedifferentiated liposarcoma. The patient was strictly observed without adjuvant therapy. During the last follow-up investigation, performed 12 months after surgical intervention, the patientbecame well with no clinical or radiological signs of recurrence. | null | Not supported with pagination yet | null |
PMC8461369_01 | Male | 19 | A 19-year-old male, with no significant past medical history presented to the emergency room with severe headache, blurred vision and confusion. Headaches began 2 months prior, with acute worsening with changes in vision for the last 3 days. He did not report fevers, cough, shortness of breath or chest pain. Originally from Honduras, the patient moved to the United States 6 months prior to presentation. He denied illicit drug use, recent trauma or injury. He denied consumption of raw seafood or shellfish. He did not report any contact with animals.
His vital signs on admission were within normal limits. Physical examination was remarkable for decreased visual acuity in both eyes with complete loss of peripheral vision in right eye. Extraocular movements remained intact. No other focal neurological deficits were noted. Initial laboratory findings revealed a normal total white blood cell count with peripheral eosinophilia of 1230/microL. Serum interferon-gamma release assay for mycobacterium tuberculosis was positive, HIV test was negative. He received the Bacille Calmette -Guerin (BCG) vaccine as a child.
A non-contrast computed tomography (CT) of the head revealed an acute parenchymal hemorrhage in the left parieto-occipital region. These findings were confirmed with Magnetic Resonance Imaging (MRI) of the brain (Fig. 1). A diagnostic cerebral angiogram did not reveal aneurysm, arteriovenous malformation, or fistula. Echocardiography did not show any evidence of endocarditis. CT angiography of the head and neck was unremarkable except for bronchiectasis in the right upper lobe of the lung. These findings prompted a CT of the chest that showed bilateral ground-glass infiltrate with cystic thin-walled linear tracks in the right upper lobe, some of which communicated with the pleural space (Fig. 2).
Subsequently he underwent a diagnostic bronchoscopy followed by a lumbar puncture. Bronchoscopic alveolar lavage (BAL) remained negative for routine bacterial, fungal, acid-fast organisms, as well as ova and parasites. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with white cell count of 315/microL, and 4% eosinophils. CSF protein and glucose were within normal limits. CSF cultures, meningitis/encephalitis polymerase chain reaction (PCR) panel as well as stain for ova and parasites was negative. Serum cysticercosis antibody as well as strongyloidiasis antibody remained negative. The serum paragonimiasis antibody by immunoblot performed at the Centers for Disease Control (CDC) laboratory came back positive. He was treated with praziquantel, along with a tapering dose of corticosteroids and anti-epileptic medication, which he tolerated well. He was discharged home in stable condition.
At his 1 month follow up visit, he reported complete resolution of headache, a significant improvement in vision loss with some residual deficit on right lateral peripheral vision. | hemorrhagic stroke in a young patient, paragonimiasis | Axial CT chest: Linear tracts and subpleural cystic lucencies present in the right upper lobe(red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article. ). |
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PMC4246684_01 | Female | 15 | The World Health Organization estimated that in 2002 there were 161 million persons worldwide with visual impairment, with 37 million of them being blind (i.e., visual acuity less than 3/60; see Resnikoff et al.,). An estimated 1.4 million were blind children below the age of 15 years (Resnikoff et al.,). Other research suggests that these numbers are higher: 259 million persons with visual impairment worldwide, including 42 million blind persons (Dandona and Dandona,). According to the World Health Organization, schizophrenia affects about 24 million people worldwide2.
Despite these large numbers of prevalence for each one of the two conditions, it has been argued that patients with CB seem to be "immune" to schizophrenia, since numerous studies have failed to produce even one well-defined case (Sanders et al.,). The aim of this section is to present such cases. We suggest that two factors are necessary in order to delimit the origin of the protective effects: (a) age of blindness onset (congenital/early vs. late) and (b) origin of visual deficit (cortex vs. globe). The PaSZ hypothesis distinguishes between two factors as well: (a) age of blindness onset and (b) degree of visual capacity (i.e., blindness, impairment, normal vision, highly trained vision, etc.). The second factor is indeed relevant in the context of Landgraf and Osterheider, where the relative risk for schizophrenia is related to a continuum of visual capacity toward a "peak risk" (see also Landgraf et al.,; Silverstein et al.,). Both sets of factors enter into the relation between schizophrenia and blindness, but in the context of the present discussion the second factor of the PaSZ hypothesis is not so crucial, because we focus on the one edge of the continuum (i.e., blindness).
As the case-reports presented in this section show, only congenital/early cortical blindness:the type of blindness that occurs when bilateral lesions of the occipital cortex deprive the individual from vision (Cummings and Trimble,, p. 110):seems to confer protective effects. A factor to be taken into consideration is the lack of uniformity in defining age of onset of early blindness. In the context of our study, the distinction between congenital/early vs. late blindness is crucial; therefore, concurring with a long line of research, we take the age of onset of congenital blindness to be birth and the mean age of onset of early blindness to be <5-6 years of age (Arno et al.,; Kitada et al.,). Following the practice in previous studies (e.g., Silverstein et al.,), these two groups are merged and collectively referred to as CB.
The case-reports and their analysis examined in the present work are the result of extensive text-mining and database searching through PubMed, OMIM, String 9.1 as well as individual journal search for all results retrieved by searches of any combination of the terms "schizophrenia," "psychosis," "congenital/early/childhood/adolescent/late/peripheral/ocular/cortical/cerebral blindness." Our searches were not constrained by any time frame or language-/ethnic-group restrictions.
Table 1 shows case-reports for three out of four groups of blindness that arise when we combine the two factors: age of onset (CB vs. late blindness) and origin of the visual deficit (cortical vs. peripheral). Although we identified cases of CB and schizophrenia, they are all of the CPB type. Our research did not identify a single case of CCB and schizophrenia, although in one case presented in Table 2 (i.e., Stewart and Sardo,) the origin of the deficit is not reported.
In Table 2, the relevant case-reports are presented in further detail. Unless stated otherwise, all case-reports involve a diagnosis of schizophrenia.
Table 2 presents five cases of CPB and one case of EPB. Starting off from Stewart and Sardo, this is the only case of schizophrenia and CB brought up in Silverstein et al. and the validity of the schizophrenia diagnosis is questioned on the basis of absence of psychotic symptoms. However, it can be observed that the patient shows disorganized speech and grossly disorganized behavior. On this basis, diagnostic criterion A for schizophrenia of DSM-5 (American Psychiatric Association,) is met even in the absence of delusions or hallucinations5. Second, the patient does seem to show psychotic symptoms that meet DSM-5 diagnostic criteria for catatonia, as these are reviewed in Tandon et al. (: Table 1). More specifically, (i) echolalia, (ii) agitation, and (iii) phases of mutism are present in the patient's behavior. The origin of the visual deficit is not explicitly reported, but crucially there is evidence that blindness run in the family. Siblings of the patient are reported to be "afflicted with the same congenital blindness" (Stewart and Sardo,, p. 125). On this basis, we are inclined to assume this is a case of hereditary blindness that involves the globe (i.e., CPB).
The second case-report that is quite explicit on the existence of psychotic symptoms is given in Gobetz. Even if Silverstein et al. are right in questioning the schizophrenia diagnosis in Stewart and Sardo, our research has uncovered case-studies where both the psychotic features and the peripheral origin of CB are explicit; the case-report presented in Gobetz is one example. The cause of CB is optic atrophy. The patient was first hospitalized in the age of 15 and the medical reports make reference to psychotic features such as hallucinations and paranoid thinking. The extensive reference to the contents of her hallucinations leaves no doubt that this is indeed a case of comorbidity between CPB and schizophrenia, with psychotic features present.
Third, Kerschbaumer presents three cases of schizophrenia and CB. The cause of blindness is eye underdevelopment. Kerschbaumer does not offer the profile of the three congenitally blind patients in terms of psychosis. However, the comments offered in the Conclusion Section (point 9) of that medical report do not offer any reason for challenging the diagnosis of schizophrenia. More specifically, Kerschbaumer draws attention to the need to avoid the misdiagnosis of the catatonic type of schizophrenia as manic-depressive psychosis or the misdiagnosis of early schizophrenia with predominant somatic delusions as psychoneurosis with paranoid ideation. It seems that the diagnoses of schizophrenia have been made with the necessary caution so as to not misrepresent cases falling within the schizophrenia spectrum disorders as schizophrenia. On this basis, we do not have any reason to question the diagnosis of schizophrenia that is given in Kerschbaumer.
Last, Weiss et al. report a patient who at the age of 6 (upon going to school for the first time) was found to be "almost completely blind" (p. 259) and transferred to a special school. This case is less clear than the ones presented above for two reasons: first, the age of blindness onset is not birth, and second, the patient is almost blind, but not completely. Putting this case-report in the context of the PaSZ hypothesis, almost complete blindness should fall within the low-risk zone for developing schizophrenia identified in Landgraf and Osterheider (: Figure 1). With respect to the age factor, the absence of consensus across studies with respect to the age range that corresponds to "early blindness" makes it hard to unambiguously say whether 6 years of age classifies as early or late blindness. Depending on where one puts the limit on the age range, the patient in Weiss et al. may or may not count as early blind schizophrenic.
Overall, the conclusion to be drawn from these case-reports is that there are cases of comorbidity between congenital and early PB (i.e., CPB) and schizophrenia, but so far no such case has been discovered for congenital or early CB (i.e., CCB) and schizophrenia.
Usher syndrome is in part the ground on which Silverstein et al. comment on cases of congenital deafblindness by arguing that it is not clear at present why adding deafness to a case of congenital blindness lifts the protective effects against schizophrenia. As shown in Table 2, not all cases of CB and schizophrenia involve hearing loss. In light of this, deafness cannot be viewed as lifting the protective effect, since the latter appears lifted in cases that deafness is not reported. According to the US National Institute on Deafness and Communication Disorders, Usher syndrome is the most common condition affecting both vision, via retinitis pigmentosa, and hearing6. In the literature, one finds numerous reports on the relation between retinitis pigmentosa and schizophrenia (Shukla et al.,; McDonald et al.,). Recently, an association between usherin and psychotic symptoms has been established on the basis of a genetic analysis of two siblings with Usher syndrome and schizophrenia (Domanico et al.,).
Bardet-Biedl syndrome presents a similar picture. It has been referred to as Laurence-Moon-Bardet-Biedl, but Laurence-Moon and Bardet-Biedl are now recognized as separate entities, although not always (Moore et al.,). Blindness that is the result of childhood-onset retinitis pigmentosa and schizophrenia-like psychosis can co-exist in Bardet-Biedl syndrome (Weiss et al.,). The main symptoms of this syndrome are rod-cone dystrophy (atypical retinitis pigmentosa), postaxial polydactyly, mental retardation, hypogonadism, and renal dysfunction (Green et al.,; Beales et al.,). Language delays have been observed too (Chen et al.,; Aloulou et al.,). Case-reports indicate comorbidity between (Laurence-Moon-)Bardet-Biedl and schizotypal traits: Delusions of persecution have been reported (O'Mahony,), but also full-blown schizophrenia (Jain and Garg,).
Disrupted-in-Schizophrenia1 (DISC1) is one of the most frequently discussed susceptibility loci for schizophrenia. It could be described as the standard textbook example of a candidate gene for vulnerability in schizophrenia (e.g., Black and Andreasen,, p. 78). Numerous studies have found positive evidence of association between schizophrenia and genes encoding DISC1-interacting proteins across a variety of ethnic groups (Bradshaw and Porteous,). Crucially, DISC1 plays a "role in radial neuronal migration via anchoring dynein motor-related proteins to the centrosome, including NDEL1, BBS1 and BBS4, two of the proteins mutated in Bardet-Biedl syndrome" (Ishizuka et al.,, p. 92; see also Kamiya et al.,). In other words, the genetic basis of Bardet-Biedl suggests that this is a syndrome that may manifest comorbidity between schizophrenia and retinitis pigmentosa.
Our review of case-reports in different syndromes suggests that schizophrenia and, more generally, schizotypal features can be found in the CB population as long as the cause of blindness is found in the globe. The situation is less clear in cases of CCB; in the absence of case-reports that involve both CCB and schizophrenia, the PaSZ hypothesis (Landgraf and Osterheider,) can be maintained. Aiming to understand the genetic underpinnings of the patterns of comorbidity presented in this section, the next section elaborates on the genetic underpinnings of these patterns and the brain structures involved in the interplay between blindness and schizophrenia. | language, occipital cortex, protective effects, schizophrenia, thalamus, vision | Not supported with pagination yet | null |
PMC4904562_01 | Male | 26 | A 26-year-old man was admitted with a 6-hour history of rapidly developing erythematous, severely painful, mildly to moderately edematous skin rash. The rash started from his right lower back and spread within hours to include the right hip, abdomen, and groin, and down to the proximal third of the anterior lateral aspect of right thigh. At the time of initial infectious diseases consultation, the skin lesion had further spread from the upper third of his right thigh to the upper edge of his right knee over the course of 40 minutes. The patient complained of extreme fatigue; however, he denied any fever, nausea, vomiting, coughing, shortness of breath, dysuria, or sick contacts. He also denied any history of allergy, tobacco use, alcohol consumption, or intravenous drug use. His medical history revealed a history of a mixed connective tissue disease (limited systemic sclerosis overlapping with polymyositis and SLE which had been diagnosed one month previously). He was currently being treated with intravenous immune globulin (IVIG) every three months and prednisone 40 mg daily. He had received a pulse infusion of 1 gram of cyclophosphamide 18 days prior to the current presentation.
His initial vital signs were stable, with temperature of 36.2 C, blood pressure of 123/82 mmHg, heart rate of 114/min, respiratory rate of 22/min, and oxygen saturation of 92% on room air. The patient was alert and oriented. Further physical examination revealed marked erythema over his right lower back, right hip, abdomen, and groin area, as well as the anterior lateral aspect of right thigh. The overlying skin was warm, mildly edematous, and extremely tender when palpated. No sign of crepitus was identified. The patient was neurovascularly intact in both lower limbs. Laboratory studies included a white blood cell count of 6.0 x 109/L, absolute neutrophil of 5.8 x 109/L with left shift noted, hemoglobin of 94 gm/L, platelets of 174 x 109/L, sodium of 130 mmol/L, potassium of 4.1 mmol/L, creatinine of 58 mumol/L, lactate of 2.9 mmol/L, creatine kinase of 661 U/L, and C-reactive protein of 99 mg/L. His hepatic profile revealed elevated alanine aminotransferase of 83 U/L and alkaline phosphatase of 321 U/L. Coagulation study showed normal prothrombin time and an elevated partial thromboplastin time of 47 seconds (22-35 seconds).
The patient was empirically started on piperacillin-tazobactam 4.5 gm IV every 6 hours and vancomycin 500 mg IV every 12 hours which cover broadly for Gram negative and Gram positive organisms including methicillin-resistant Staphylococcus aureus (MRSA), along with clindamycin 600 mg IV every 8 hours. Clindamycin was given to inhibit the toxin production from possible invasive Streptococcus pyogenes based on available human and animal studies. One dose of IVIG was given since he was due for his routine dose for his rheumatological disorders, and given that IVIG may improve outcomes of necrotizing fasciitis from GAS infection. Tissue biopsy of fascia from the anterior and lateral side of right thigh was performed by the orthopedic surgery team at the bedside under local anesthesia and was sent for urgent frozen section pathology and microbiology. Both tissue and blood sample cultures grew Streptococcus pneumoniae sensitive to penicillin. Pathological findings with heavy neutrophilic infiltration and abundant necrosis within fat and fascia were consistent with necrotizing fasciitis. Contrast computerized tomography of the abdomen and pelvis was performed after tissue biopsy suggesting postbiopsy changes without obvious infection involving fascia or muscles. Based on the patient's rapidly developing clinical symptoms and evidence of necrotizing fasciitis on tissue biopsy, he was taken to the operating room urgently. During surgery, he was found to have extensive edema of his subcutaneous tissue, but with no obvious fascial or muscle necrosis. Therefore, no debridement was performed. Fascial tissue from the anterior and lateral side of right thigh was randomly sampled intraoperatively and clear evidence of necrotizing fasciitis with significant neutrophilic infiltration and necrosis in fat and fascia was confirmed by pathological results, as shown in Figure 1. Clindamycin and vancomycin were discontinued on the second day after the microbiology culture results became available. Piperacillin-tazobactam was switched to ceftriaxone which was continued to complete the course of 6 weeks of treatment. The patient required 8 days of postoperative ICU stay which was complicated by methicillin-sensitive Staphylococcus aureus (MSSA) pneumonia, coagulopathy with factor XI deficiency, and a flare-up of his rheumatologic condition. He recovered well with subsequent physiotherapy on the medicine ward and later in the rehabilitation unit. | null | Not supported with pagination yet | null |
PMC9761204_01 | Male | 59 | A 59-year-old Indonesian man was first diagnosed with pulmonary tuberculosis (TB) in 2011, he completed a full course of category 1 treatment of 2RHZE/4RH (rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E)) and was considered cured. In January 2018 he experienced chronic productive cough with night sweats. His physical examination was unremarkable. His initial sputum GeneXpert showed drug-susceptible Mycobacterium tuberculosis. Chest x-ray was performed, showing perihilar lung infiltrates (Figure 1). He was treated with category 2 treatment of 2RHZES/1RHZE/5RH (rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), streptomycin (S)). On the fourth month of treatment, his GeneXpert evaluation showed rifampicin resistant (RR) and was referred to an Indonesian tertiary-care hospital for initiation of MDR-TB treatment.
Choosing the appropriate MDR regiment for this patient was challenging due to his multiple comorbidities, namely: untreated chronic hepatitis B, which developed into decompensated liver cirrhosis (he was diagnosed with hepatitis B in 2011 but only began treatment with tenofovir disoproxil fumarate 300 mg q.d in January 2018); type 2 diabetes (treated with insulin); diabetic retinopathy; and osteoarthritis of right knee. Second-line injectable drugs (SLID) and ethambutol were used in his previous regimens, thus were omitted. Pyrazinamide, ethionamide/prothionamide, and p-aminosalicylic acid (PAS) were omitted due to liver cirrhosis. At the time of his MDR treatment initiation, the 2018 World Health Organization (WHO) guideline was not yet published, thus his MDR regimen was designed based on the 2016 WHO guideline. He started his MDR treatment in July 2018 (baseline body weight: 60 kg), which included levofloxacin 875 mg OD, cycloserine 875 mg OD, bedaquiline 400 mg OD for 2 weeks followed by 200 mg OD until the sixth month of treatment, linezolid 600 mg OD, isoniazid 600 mg OD, and pyridoxine 200 mg OD. Monitoring of adverse drug reaction was performed every 2-4 weeks throughout treatment period, which consisted of, but not limited to: symptom recording, routine physical examination, retinal examination, ECG, complete blood count, liver transaminase levels, bilirubin level, and renal function test. On the second month of treatment, he developed thrombocytopenia without bleeding manifestation due to linezolid-induced myelosuppression. Linezolid was stopped for 2 weeks and his platelet count increased from 36,000/microL to 90,000/microL. Linezolid was reintroduced with lower dose of 300 mg OD. On the seventh month of treatment, he developed severe depression with visual hallucination, which improved after the addition of risperidone 1 mg BID and dose reduction of cycloserine from 875 mg to 500 mg OD. On the 10th month of treatment, he developed pancytopenia due to linezolid-induced myelosuppression. Linezolid was postponed for 2 weeks and reinitiated after resolution of pancytopenia. On the 14th month of treatment, he experienced partial vision loss which was later diagnosed as linezolid-induced optic neuritis. Linezolid was substituted with clofazimine 100 mg OD. Clofazimine was considered as the best option because during this period the 2018 WHO guideline was published and reclassified clofazimine as group B medication (previously as group C medication in 2016 guideline). Since the 14th month of treatment, the regimen of levofloxacin 875 mg OD, cycloserine 500 mg OD, clofazimine 100 mg OD, isoniazid 600 mg OD, and pyridoxine 200 mg OD was maintained until the end of treatment with minimal side effect. He was considered cured after 3 separate negative sputum culture results with total treatment duration of 26 months. Sputum culture and drug susceptibility testing was performed in a government-run out of hospital laboratory. We were unable to receive on time culture result due to technical problems faced by the local laboratory which resulted in the longer treatment duration than the recommended 18-24 months. His complete treatment timeline is sumarized in Figure 2. | mdr-tb, adverse events, multiple comorbidities, treatment modification | Not supported with pagination yet | null |
PMC6260376_01 | Female | 14 | The patient was a 14-year-old multi-sport female athlete (soccer and handball) complaining of sharp pain in the right side of the groin region, after an acute injury during a handball game. The injury caused by a sudden forceful eccentric contraction of the hamstrings, in a split movement, attempting to save a shot at goal. The pain was concentrated at the insertion of the hamstring and adductor magnus muscle, at the ischial tuberosity. Aggravating activities included walking, stair climbing, and prolonged sitting. Past medical history was unremarkable. Her general practitioner (GP) had suggested resting the injury. Due to ongoing pain and lack of functional progression, she consulted a physiotherapist in private practice, two weeks after the initial trauma. At the initial examination, her symptoms were beginning to subside, and daily function was improved, therefore conservative treatment was continued, focussing on strengthening the hip rotators, flexors, and adductors. The conclusion of the physiotherapy examination was a possible trauma to the pubic symphysis, and subsequently referred to a sports physician for further evaluation, and conservative treatment was prescribed.
Almost three months after the initial trauma, she felt a sharp pain at the initial injury site, and her functional capability decreased significantly. After a renewed specialist consultation, she was referred to MRI. The MRI revealed an avulsion fracture of the tuber ischiadicum, and consequently she was referred on to the orthopaedic sports clinic for further evaluation.
Initial examination at the sports clinic revealed that she was unable to do a 20 cm step up, run, cycle, nor walk 1.5 km. Full knee and range of motion (ROM). Distinct palpation pain at the medial side of the right Ischial tubercle. Maximum internal and external hip rotation produced sharp pain at the Ischial tubercle. Isometric knee flexion and extension strength, tested by handheld dynamometer at 60 of knee flexion, exhibiting a 50% decrease in strength, compared to the left leg. The patient's Lower Extremity Functional Scale (LEFS) score was 38/80, with a score of 80 translating to no deficits. X-ray imaging was prescribed, which confirmed the fracture seen on MRI. (Fig. 1)
There remains variability in the definitions of fracture-healing. In the study conducted by Bhandari and colleagues, surgeons felt confident of predicting non-union fractures of the pelvic rami by the fourteenth week. Pain on weight-bearing (more than three months after fracture for a delayed union and more than six months after fracture for a non-union) was endorsed as the most consistent predictor of delayed union and non-union fractures.There is as yet no consensus of the definition of non-union fractures,as several factors need to be considered in defining delayed or non-union fractures, rather than a specific timeline. This avulsion fracture may therefore be classified as a non-union.
An ultrasound-guided steroid injection (1 mL Depomedrol,3 mL Lidocaine) was administered at the insertion of the medial hamstring and adductors to the ischial tuberosity. After ten minutes, the patient could do a step-up and a full squat with no pain, however the effect subsided after two weeks. The rationale for applying the steroid injection being to eliminate the possibility of referred pain.
Nine months after injury a surgical procedure was performed with the patient in general anaesthesia and lying on her left side to induce a strong healing response at the non-union. An ultrasound guided percutaneous fenestration with K-wire 1.6 mm was repeated 6 times at the avulsion fracture. The enthesis was fenestrated 10 times, using a 1.2 mm syringe. Finally, a 5 ml local anaesthetic was injected in the area. The procedure lasted 20 min in total. The novelty of the method being the use of a K-wire in repairing a non-union, as opposed to the percutaneous needle tenotomy, in which percutaneous needle fenestration is performed at the fracture site, inducing a healing response prior to considering operative fixation of the non-union fracture. Other methods of operative interventions may include reconstructive anchor re-fixations, resection procedures of the non-united fragments, resections and osteostimulating donor site drilling and partial hamstring releases for traumatic hamstring syndrome (Fig. 2).
Rehabilitation in the primary sector was adapted by the work of Shoensee and Nilsson. Following the fenestration with K-wire, the patient was placed on crutches and was instructed to remain non-weight bearing and avoid sitting directly on her right buttock for two weeks. The rehabilitation progression was based on proposed healing rates of bone as well as by pain symptoms. Approximately six weeks' post intervention pain ceased when walking slowly. Three months postoperative she reported pain free sitting and walking distance of 500 m. Subsequent rehabilitation focused on functional movement, flexibility and strength training of abdominals, hips and lower extremity. Pain presentation and clinical findings 6 months postoperative was normal ROM and slight palpation tenderness on the ischial tubercle. Pain free squats, lunges, and slight tenderness during kicking and fast cutting movements. 17 months after the trauma, and 8 months postoperative she was cleared for a slow return to football, being pain free in running, cycling and sitting. Lower Extremity Functional Scale had improved to 77/80 as illustrated in Fig. 3. | adolescent apophyseal injury, fenestration, ischial tuberosity avulsion, non-union, sports injury, trauma | Not supported with pagination yet | null |
PMC6579729_01 | Male | 7 | A 7-year-old male child was presented to the Pediatric Department in Shatbi University Hospital with recurrent chest infections since 1 year. Repeated chest X-ray showed left pleural effusion. The child was managed conservatively and discharged from the pediatric department. During the course of follow-up for the respiratory condition an abdominal ultrasound was ordered to investigate a new onset minor abdominal discomfort. An abdominal cyst was found which, otherwise, was not clinically palpable during abdominal examination. Subsequent computed tomography (CT) scanning of the abdomen and pelvis with intravenous contrast revealed a retroperitoneal thick-walled fluid filled mass, measuring approximately 11.5 x 13 cm in close relation to the main pancreatic duct with inflammation of the adjacent pancreatic tissue. Provisional reports indicated a pseudo-pancreatic cyst with further extension into the posterior mediastinum through one of the diaphragmatic hiatus ( Fig. 1 ). Serum amylase and lipase were markedly elevated (amylase: 45,630 U/I and lipase: 180,000 U/I).
The decision after surgical consultation was to perform laparotomy. The child was prepared for the operation. Through an upper midline incision, the abdomen was explored. This revealed a large, smooth, and fluctuant mass behind the stomach extending up to the posterior mediastinum through the esophageal hiatus, mostly arising from the pancreas. Aspiration of the coffee ground contents was done followed by a drainage procedure by anastomosing the posterior wall of the stomach to the anterior wall of the cyst wall (cystogastrostomy) using running 4/0 vicryl sutures. A Penrose drain was inserted in the left upper quadrant followed by a layered closure. The postoperative course was uneventful. Nasogastric suction and intravenous fluids were continued for 5 days, after which oral feedings were gradually given. The drain was removed after 5 days and the child was discharged from the hospital on the 9th postoperative day. Follow-up abdominal ultrasound was done after 2 weeks and revealed dramatic improvement regarding the size of the cyst. Serum amylase gradually fell to the normal limits. A repeat ultrasound confirmed complete resolution of the cyst after 6 months. The patient is doing well after 1 year of regular follow-up visits. | cystogastrostomy, mediastinal extension, pancreatic pseudocyst | Not supported with pagination yet | null |
PMC8411640_01 | Male | 45 | A 45-year-old HIV negative male immigrant from Mexico presented to our emergency department complaining of progressive bilateral lower extremity weakness for one month with increasing difficulty walking and decreased sensation below the nipple level over the preceding two weeks. He reported urine and stool retention over the preceding one week. He denied cough, shortness of breath, or fevers/chills but did complain of night sweats for the past one month. On physical exam he was found to have profound diffuse bilateral lower extremities weakness (2/5) and diminished sensation to light touch and pinprick below the level of T4-T5. There was no lymphadenopathy appreciated on examination. Initial work up included a white blood cell count of 12.6, platelet count of 494, C-reactive protein of 2.6 mg/dl, erythrocyte sedimentation rate of 20, and a positive QuantiFERON (cutoff value of 0.35 IU/ml). A set of blood cultures was negative. HIV immunoassay testing was negative. Gadolinium enhanced magnetic resonance imaging (MRI) of the thoracic spine demonstrated evidence of T3-T4-T5 osteomyelitis with epidural abscess and bony destruction of the T4 and T5 vertebral bodies, resulting in severe spinal canal stenosis and spinal cord compression (Figures 1 and 2).
The patient underwent emergency decompression of the epidural abscess with multi-level pedicle screw instrumentation for thoracic vertebral stabilization and interbody cage placement (Figure 3). Intraoperative findings were more consistent with a chronic fibrotic process with a solid mass adherent to the thecal sac with only a small amount of liquid abscess encountered. Epidural tissue biopsies showed caseating and non-caseating granulomas (Figure 4). Further pathology results showed no organisms on acid fast bacilli (AFB) and Grocott methenamine silver stains. M. tuberculosis was not detected on polymerase chain reaction (PCR) (GeneXpert assay) testing of the surgical specimen. The epidural abscess cultures were positive for pan susceptible Streptococcus anginosus at 48 h on multiple tissue samples. A transthoracic echocardiogram did not show evidence of endocarditis. A computed tomography chest showed clear lung parenchyma and multiple sputum samples were negative for AFB stain and culture. Genitourinary testing for TB was not performed given lack of genitourinary symptoms. Approximately 6 weeks after the tissue biopsies were obtained, mycobacterial cultures grew pan susceptible M. tuberculosis. The patient completed six weeks of intravenous ceftriaxone for treatment of S. anginosus and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy. At hospital discharge the patient had persistent bilateral lower extremity weakness requiring a walker for ambulation, and these deficits improved with outpatient physical and occupational therapy. He was lost to follow-up before completion of RIPE therapy. | streptococcus anginosus, case report, epidural abscess, spinal tuberculosis | Not supported with pagination yet | null |
PMC9397879_01 | Male | 40 | A 40-year-old male with a chronic cervical SCI participated in this study. Prior to enrollment, his injury, which occurred 12 years before recruitment, was graded as ASI A, with a C4 neurological level of injury, according to the International Standards for Neurological Classification of SCI (ISNCSCI).
This study was approved by the Human Subjects Ethics Sub-committee of the Hong Kong Polytechnic University (HSEARS20190121002; 9 Feb 2019) and the participant provided written informed consent.
This study implemented a two-phase crossover design. After a two-week baseline period, the first phase involved five weeks of tSCS training three times per week, and a second phase introduced BCI motor priming before tSCS training for a further five weeks (Figure 1A). There was a two-week washout period between phases, and a follow-up assessment was conducted 4 weeks after the end of the second phase.
Hand and arm training consisted of repetitive uni- and bimanual exercises in conjunction with tSCS. A typical session focused on a number of grasp types, including palmar grasping, pinching, pinching with rotation, and finger isolation. Tasks included flipping playing cards, moving ping pong balls between containers, scooping rice with a spoon, and stacking blocks, among others. Tasks were adjusted relative to functional improvements to maintain a degree of difficulty. For example, ping pong balls were replaced with marbles and then by small beads as the study progressed. Hand training was performed continuously over the 60-min session with two brief pauses when the participant was given a break from tSCS.
A constant current stimulator (DS8R; Digitimer, Oxford, United Kingdom) delivered stimulation in bursts of ten 100 mus long biphasic rectangular pulses at a frequency of 30 Hz, reflecting recent clinical work. Two round cathode electrodes (3.2 cm; Axelgaard Manufacturing Co, Fallbrook, CA, USA) were positioned at and below the level of injury between (i) C4 and C5, and (ii) C5 and C6 spinous processes. Cathodes were fastened to the skin with hypoallergenic tape to ensure a snug contact throughout the session. Inter-connected anode electrodes (8.9 x 5.0 cm; Axelgaard Manufacturing Co, Fallbrook, CA, USA) were placed symmetrically on the shoulders, above the acromion. In order to increase the likelihood of activating spinal structures, which lie below multiple layers of skin, fat, muscle, and vertebrae, stimulation intensity was set to highest tolerable degree (mean +- standard deviation; C4-C5: 49.0 +- 4.6 mA, C5-C6: 40.8 +- 5.1 mA). Current intensity was determined at the beginning of each session by gradually increasing the current from zero mA in 2.5 mA increments. This continued until the participant verbally communicated that the stimulation was causing a painful sensation, as indicated by reference to the fifth increment (moderate-severe discomfort) of the Visual Analogue Scale for pain intensity. The participant reported habituation after prolonged stimulation, therefore stimulation intensity was re-evaluated after 10 min.
Stimulation was applied for a total of 60 min during each session. To avoid heating and skin irritation from prolonged high-intensity stimulation, there was a 2-min break every 20 min where the stimulator was switched off. Hemodynamic parameters (blood pressure and heart rate) were monitored during breaks to track any incidence of autonomic dysreflexia.
To motivate the participant to engage in motor priming, as well as record sensorimotor rhythms, we devised a game-like brain-computer interface priming paradigm based on the "BCI2000" platform. The participant positioned his wheelchair opposite a computer screen and was fitted with an EEG cap, as shown in Figure 1B. Conductive gel was injected into each electrode and signal quality was verified by visual inspection. Modulation of beta band power (14-25 Hz) from the participant's electroencephalogram (EEG) was used to guide a virtual basketball toward one of two targets. The participant underwent 300 repetitions of the priming task, divided into 10 runs, each separated by 10-60 s breaks to avoid fatigue. Each repetition, or "trial", began with a photo-realistic basketball at the center-left of the computer screen, and a target either at the top-right or bottom-right (see Figure 1C). The ball moved horizontally at a fixed rate from left to right. The participant attempted mirror symmetric bimanual finger flexion and extension to push the ball to the upper target and relaxed for the ball to fall downwards. The participant was encouraged to imagine the sensation of clutching a real basketball as they performed the movement, in line with kinesthetic motor imagery protocols. Each trial lasted for 4 s and there was a 1.5-2.5 s inter-trial interval. Once priming was completed, the electrode gel was removed from the participant's hair, and the participant immediately proceeded to tSCS training.
In order to control the onscreen ball, EEG was recorded with a biosignal amplifier (g.USBamp; gtec, Schiedlberg, Austria) at a sampling rate of 256 Hz from ten active electrodes positioned at FC3, FC4, C1, C2, C3, C4, C5, C6, CP3, and CP4, according to the international 10-10 system. Electrode AFz was used as ground and the reference electrode was placed on the right earlobe. Through the BCI2000 platform, incoming EEG were spatially filtered with a small Laplacian filter to enhance the spatial resolution at electrodes C3 and C4, approximating the area above the sensorimotor cortices. The spatially filtered data was transformed into the frequency domain using an autoregressive spectral estimation. The mid-beta frequency band (18-26 Hz) was found to be the most reactive band during movement and was used to influence the vertical trajectory of the ball. The sum of spectral power from electrode C3 and C4 was found every 50 ms from a 400 ms long window and vertical cursor control was determined by solving a linear equation. A detailed explanation of this procedure was described by Wolpaw and McFarland. A 5-min calibration session at the beginning of each session trained the program to classify between attempted movement and rest. The setup was identical to that of the above priming strategy. However, the ball only moved in the horizontal direction, with no vertical displacement.
The current setup required 30 min for BCI priming, including 10 min for setup and 5 min for equipment removal. The tSCS component required around 10 min to apply electrodes and establish stimulation parameters. Including breaks, a session of BCI priming with tSCS never exceeded 100 min.
The Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and grip strength were the primary measure of functional outcome. Grip strength was measured with the Vive Precision grip strength tester (Vive Health, Naples, FL, USA). GRASSP tested the strength of upper-limb muscles (Anterior deltoid, elbow flexors, elbow extensors, wrist extensors, extensor digitorum (DIII), opponens pollicis, flexor pollicis longus, finger flexors (DIII), finger abductors, first dorsal interossei), sensation on the dorsal and palmar sides of the hands, and fine and gross motor skills, quantified by scoring functional tasks (these included grasping and pouring water from a bottle, unscrewing the lids from jam jars, moving pegs between holes, inserting and rotating a key in a lock, inserting coins into a slot, screwing a nut onto a bolt).
Secondary outcome measures included the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), and the Spinal Cord Independence Measure (SCIM).
Further, the Modified Ashworth Scale (MAS) was used to quantify spasticity in the following upper-limb movements: shoulder abduction, elbow extension, elbow supination, wrist extension, and finger extension. The assessment was performed with the participant in the supine position and a trained physiotherapist graded each movement depending on the level of rigidity during flexion and extension. The minimum and maximum score for each unilateral movement was 0 (no spasticity) and 4 (velocity-dependent resistance to movement). A score of 1.5 was given when 1+ was selected [a detailed description of the MAS assessment was given by Charlambous et al. ]. The sum of scores from the left and right side were found for each movement.
All outcome measures were performed at the beginning and end of each intervention phase. Primary outcome measures were also performed in the middle of each five-week phase, and again at a 4-week follow-up session. Primary outcome measures were measured twice at baseline: once two weeks prior to the beginning of the first intervention phase, and once immediately before the first training session (refer to Figure 1A). Functional outcome measures were performed on different days from hand training sessions, and stimulation was not applied during any assessments.
An offline analysis of the participant's EEG during BCI motor priming was performed to determine if sensorimotor cortical activity was modulated during and/or across sessions. EEG was first band-pass filtered from 1 to 40 Hz with a 3rd order Butterworth filter. Next, we calculated the power spectrum density during each trial, that is, from one to three seconds relative to the appearance of the ball (t=0 s). The pre-trial period (-1.5 to -0.5 s) was also found relative to the appearance of the ball. The mean power across the beta band (18-26 Hz) was subtracted from and divided by the mean of the resting state beta power to give the percentage ERD/ERS relative to pre-trial power. | brain-computer interface, motor priming, neuromodulation, rehabilitation, spinal cord injury, transcutaneous spinal cord stimulation | Not supported with pagination yet | null |
PMC9130855_01 | Male | 39 | In January, a previously healthy 39-year-old man was brought to our emergency department with a 1-week history of pain and ulceration in his left calf. He developed a sudden pain in the left lower extremity after exercise a week ago, followed by a high fever (40.0 C) with dizziness, nausea, and shortness of breath. Lower limb pain increased gradually, accompanied by swelling and skin lesions. Twenty-four hours before the visit, the patient showed anuria. Physical examination in the emergency room detected tachycardia (112 bpm) and hypotension (72/39 mmHg). The patient was rapidly admitted to the ICU at the midnight. He was an ex-tobacco smoker for 3 years and drank a little beer sometimes. No other history was recorded, including tumors, organ transplants, immunodeficiency, diabetes, toxic exposure, insect stings, or trauma. Arterial blood gas indicated metabolic acidosis with respiratory alkalosis with a pH of 7.404, and lactic acid of 7.1. His initial blood test results were as follows: white blood cells, 21.33*109/L; hemoglobin, 134 g/L; platelets, 44*109/L; laboratory studies also showed elevated plasma C-reactive protein levels (541.0 mg/l), while procalcitonin and interleukin-6 (IL-6) levels exceeded the limit of detection (>100 ng/mL and >5000 pg/mL, respectively). Other laboratory tests showed low albumin (20.2 g/L), high serum creatinine (219 mumol/L), elevated serum creatine kinase (1813 U/L), dysfunction of coagulation (INR1.33, PT16.6 s, APTT 66.8 s), and elevated D-dimer (3.7 mg/L). On physical examination, moderate swelling, hemorrhagic blisters and bullae, marked pain with movement, and overlying erythema of his left lower limb were found (Figure 1). Computed tomography (CT) showed diffuse subcutaneous soft tissue lesions in the lower leg and pneumonia. Transthoracic echocardiography demonstrated normal left ventricular function. No abscess was found.
The patient was diagnosed with septic shock due to necrosis of the skin and deep soft tissue of the left extremity. He immediately received meropenem and daptomycin treatment empirically, fluid resuscitation, and noradrenaline via an internal jugular central venous catheter. Continuous hemodiafiltration was also implied. Although sepsis was diagnosed, the pathogen of the initial infection was unclear. Before the use of antibiotics, cultures, as well as the rapid pathogen detection by metagenomic next-generation sequencing (mNGS), were drawn from the pustule, deep soft tissue (lower limb), and two-site blood samples (both aerobic and anaerobic bottles) at least twice. Cultures were performed by experienced laboratory operators in a standard manner and the mNGS tests were performed following the manufacturer's instructions. Generally, standard samples were handled with quality-filtered, elimination of duplicate readings, removal of low-quality sequences that match human genome sequences. Libraries for mNGS were prepared using the Illumina DNA Prep, (M) Tagmentation (20018705, Illumina) according to the manufacturer's recommendation. Pooled libraries were sequenced on NextSeq 550Dx system using a 75 bp, single-end sequencing kit (Illumina), and at least 20 milslion sequencing reads were acquired for each sample. A negative control sample was processed and sequenced in parallel in each sequencing run for quality control. The data was processed using PIseqTM (Pathogen Identification Sequencing) Metagenomic Sequencing Data Management System V2.0 (WillingMed) simultaneously to draw the conclusion. However, although the patient's hemodynamics was gradually improving after the antibiotic treatment, the area of redness and swelling of the left lower limb gradually spread to the root of the thigh and perineum (Figure 1). Moreover, the patient developed moderate acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 ratio of 152.5 mmHg and high-flow nasal oxygen (HFNO) was used to improve hypoxemia. There's also liver function damage with total bilirubin levels (TBIL) significantly increased. On the third day after admission, the mNGS results showed GAS both in pustule and deep soft tissue (Table 1). The pustule mNGS report detected a total of 132 unique GAS sequence reads, representing 96.3% of microbial reads and 0.49% of the nucleotide sequence coverage. The soft tissue mNGS report identified a total of 142474 unique GAS sequence reads, representing 100% of microbial reads. The virulence profiling and antimicrobial genes report were also presented (Supplementary Table 1). Thus, we diagnosed this patient as having streptococcal toxic shock syndrome based on the criteria (shown in Supplementary Table 2) and necrotizing fasciitis. Other tests for pathogens such as parasites, epidemic hemorrhagic fever, leptospirosis, tuberculosis were all negative. Therefore, antibiotic therapy comprising piperacillin/tazobactam (4.5g Q6H/day) and clindamycin (900mg Q8H/day) instead of meropenem was given immediately. Because of the low platelet count and disorder of coagulation, the surgeon had to postpone the surgical debridement while observing the tension of the wound closely. Meanwhile, he received intravenous immunoglobulin (IVIG) 0.5g/kg/day for 5 days. Over the next 5 days, his kidney function and coagulation were recovered and the general condition was improved subsequently. The temperature dropped to the normal range, too. Ten days after admission, as the PaO2/FiO2 ratio increased to 311 mmHg, HFNO could be stopped. At this time, magnetic resonance imaging (MRI) was taken and showed diffuse swelling in bilateral buttock, erector spinal muscle, left thigh root, left lower limb muscle, and muscle space (Figure 2). Three days later, he received the first surgical debridement and then was transferred to the general ward. The patient underwent another debridement surgery and the following skin grafting during the hospitalization. After the operations and rehabilitation exercises, he is now recovering well and ready to be discharged from the hospital. During the patient's stay in the ICU, the results of the cultures were all negative in the blood, pustule, and deep soft tissue. The clinical course with laboratory results and treatments was concluded in Figure 3. | clindamycin, intravenous immunoglobulin, invasive group a streptococcal infections, next-generation sequencing, streptococcal toxic shock syndrome | Not supported with pagination yet | null |
PMC3871413_01 | Female | 21 | In 2008 a 21-year-old female, National Collegiate Athletic Association (NCAA) university basketball point guard sustained a concussion in the second game of her junior season. The athlete was pinned between two players and was subsequently struck on the left side of the frontal bone. She was fouled on the play, and recalled feeling dizzy and lightheaded at the time, but was composed enough to make both free throws, and complete the rest of the game. Immediately following the game, her chief complaints were headache, nausea, loss of appetite, and fatigue. Following the game, at the team dinner, her teammates noticed that she was uncharacteristically quiet. She also felt tired, experienced a lack of appetite and the onset of a headache. As the night progressed the athlete began to feel nauseated and had an increase in what she described as a "hazy" feeling. Also, when she returned to the hotel room where the team was staying, she felt confusion and began crying for no particular reason for which she was aware. Before retiring to bed she took ibuprofen.
There was no certified athletic trainer (ATC) traveling with the basketball team for this road trip and the athlete did not report her symptomatology to either the coaching staff or to the ATC at the tournament. She did however report to a teammate, when her behavior was questioned, that she thought it was possible she had a concussion. It is of note that the athlete was an athletic training student in her University's athletic training education program (ATEP) and had knowledge of concussion signs/symptoms.
The day after the blow to the head, the athlete participated in another game at the tournament. She performed at an uncharacteristically low level during this game as, typically, she was an aggressive player and did not perform in the same manner. She stated that she may have hit her head during this second game, but she was unsure. She fouled out early in the game, in part because she was called for three charging fouls. The athlete claimed that these came from her lack of depth perception; without perceiving where the opposing players were in relation to her affected her contact with them.
The following day the team returned from their tournament. At that point, the athlete informed her ATC of the situation and the signs and symptoms she was experiencing. The decision was made to follow the guidelines given by the 2nd International Conference on Concussion in Sport ie, to follow a step-wise progression. At the time this injury occurred, these guidelines were the most current set of recommendations. While the recommendations since then are similar, there have been updated guidelines released more recently (Zurich, 2013 is the most recent set of guidelines). Likely the most applicable update is the position statement from the American Medical Society for Sports Medicine.
The case study patient missed one game and returned to play for a game in one week. This was one day shorter than if the Prague guidelines had been exactly followed. The athlete was given exertional testing, including running, and her symptoms did not return. She also reported having no symptoms of concussion, such as headache, nausea, or vision issues. In addition, computerized cognitive testing was given to the athlete and all aspects were normal compared to her baseline test.
She played 38 minutes of the 40 minutes of the game on the day that she returned to play. Following the game she was unable to leave the bench for 10 minutes. She reported a headache scoring 7 on a scale of 1-10, and all of her original symptoms had returned and were (according to her own perception) magnified compared to what they had previously been. Immediately following the game, the athlete went home and went to bed. The following day was a scheduled day off school (and practice) and the athlete spent the entire day in bed. The athlete did not report this to her ATC, her coach, or any of her teammates.
As noone was aware of her symptoms, and since she also denied any symptoms when asked by her ATC, the athlete continued to practice as usual. She later reported that her headache was a 2 on a scale of 1-10, and over the course of 2 weeks progressed to no headache at all. All of the other symptoms resolved within 1 week, even though she was participating fully in both practice and classes.
The athlete experienced no signs or symptoms of concussion after her headache resolved (3 1/2 weeks after the concussive blow). This period of no symptoms lasted for two months. Then, during a game, she experienced another blow to the head. Toward the end of the game, the athlete was chasing a loose ball and was struck by an opposing player. She completed the game and experienced a headache that was a 4 on a scale of 1-10. Again, she did not report the headache to her ATC, coach or teammates.
The season lasted for approximately 6 more weeks. During this time, the athlete repeatedly reported that she was experiencing no symptoms of concussion. However, she had a constant headache of 3 on a scale of 1-10 while at rest, and 4 on a scale of 1-10 while playing basketball. During this time she experienced a lack of short-term memory, difficulty concentrating, and a general feeling she described as being "out of it". These symptoms affected her academic performance and her grades were significantly lower compared to her normal academic aptitude.
The day that the season ended, the athlete reported to her ATC that she had been concealing her concussion symptoms and stated that she had been experiencing them over the last few months. She was referred to the team physician who saw her on a weekly basis. All physical activity was ceased and academic accommodations were made to ease her back into her studies. Another primary rule given to her by her ATC allowed her to perform only one task at a time eg, she was not allowed to listen to music while doing homework. The goal was to tax her brain as little as possible and minimize multitasking.
While it is impossible to know whether all of these limitations were fully followed by the athlete, she seemed to finally understand the gravity of her situation and expressed that she was taking the advice of her ATC and physician. In addition, her roommates and teammates validated that she was diligent in following the rules given to her at the end of the season.
The resolution of her symptoms happened over a span of 2.5 months. Each symptom's severity, including her academic performance and her headache, decreased as time went on and she gradually began to feel asymptomatic. After 2.5 months, once the symptoms were completely resolved, she was allowed to start light cardiovascular activity.
The first 2 weeks of her progression toward full return to play included only biking. The following 2 weeks she was allowed to combine biking with the elliptical machine. After those 2 weeks elapsed, she was allowed to begin a light weight lifting schedule. During this time she reported no symptoms of concussion. After that, she was allowed to start including ball handling techniques and jogging. She was cleared for full participation in basketball by the physician and ATC in mid-summer, 7 months after the original concussive blow.
The following season, the athlete was a senior on her basketball team, she had been cleared to play for five months and was experiencing no issues from her previous blows to the head. During a game, she received another blow to the head and had an immediate headache of 5 on a scale of 1-10 that she reported to her ATC, and was removed from the game. She also had a visible bump on her head. That evening she rested and took no medication. She was observed by the ATC and physician the following day. Within 24 hours her headache was a 2 on a scale of 1-10 and within 48 hours it had reduced to a 1 on a scale of 1-10. On day 3, she had no headache, and it did not return with exertional testing. She was held from basketball for one additional day. She returned to play on day 5, and reported zero symptoms of concussion.
While concussions in athletes and post-concussive syndrome are not uncommon, it is important to note several unique aspects to this story. First, the student was an athletic training student and was very cognitively aware of the risks of continuing to play while symptomatic. In addition, the patient was asymptomatic even during exertional testing and had normal computerized neurocognitive testing, and still had her symptoms return the day that she went back to play. This is a demonstration that a lack of symptoms and the presence of normal test scores does not necessarily mean that the athlete is no longer at risk when returning to play. This shows that an area of future research may be to attempt to determine at how much risk an athlete may still be at when returning to play following a concussion, even if they are symptom free and have normal cognitive testing. Also, research needs to address how best to reach athletes to help them understand the consequences of continuing to play after a concussion. | basketball, concussion, female athletes, mild traumatic brain injury | Not supported with pagination yet | null |
PMC4120058_01 | Male | 35 | A 35-year-old Native American without significant medical history was transferred from another facility for the evaluation of worsening shortness of breath, cough, and hemoptysis of over 2 months. He also had a history of on and off fever, and weight loss of about 20 pounds. He was a known smoker with a history of occasional alcohol intake. Family history was unremarkable. There was no history of recent travel or contact with tuberculosis patients. On examination, vital signs were normal. Mild pallor was noticed with trace pedal edema. A few crepitations at the right lung base were noted. Cardiac examination was unremarkable.
Laboratory examination revealed hemoglobin of 7.5 g/dL and white blood cell count of 7,900/mm3 (neutrophils 93%). Antinuclear cytoplasmic antibody (ANCA) panel and antinuclear antibody (ANA) were negative. A computerized tomography (CT) of the chest showed right-sided pleural effusion with mediastinal lymphadenopathy measuring 3.2x2.2 cm, and a ground glass density with coarsening of interstitial markings in bilateral lower lobes (Fig. 1). Pleurocentesis revealed pinkish fluid with 1,2750/mm3 red blood cells, 400/mm3 white blood cells (neutrophils 17%, monocytes 31%, and lymphocytes 45%), 1.3 g/dL protein, 80 IU/L lactate dehydrogenase, 115 mg/dL glucose, and pH of 7.49 without any malignant cells. Serum protein and glucose were 6.6 g/dL and 180 g/dL, respectively. Bronchoscopic evaluation was also done which was unremarkable.
Transthoracic echocardiogram (TTE) was done which revealed a large left atrial mass measuring 8.15x2.2 cm attached to interatrial septum on the left, causing pulmonary venous hypertension with an elevated right ventricular systolic pressure (RVSP). This was followed by a transesophageal echocardiogram (TEE) that revealed a mass completely occupying the left atrium and protruding across the mitral valve into the left ventricle with a mild mitral regurgitation. There was also invasion of the pulmonary veins. The RVSP was elevated at 120 mmHg with a severe tricuspid regurgitation (Fig. 2).
At the time of initial presentation with shortness of breath and hemoptysis, our differential diagnosis was broad and included connective tissue diseases, tuberculosis, lung malignancy, Wegener's granulomatosis, and heart failure. Bronchoscopy and CT of the chest ruled out lung malignancy. ANA, ANCA, and quantiferon tests were negative, ruling out SLE, Wegener's granulomatosis, and tuberculosis, respectively.
Cardiothoracic surgery was consulted for surgical excision of the mass, and the patient underwent a limited excision of the mass along with mitral valve repair. A post procedure TEE showed an improvement in the RVSP of 47 mmHg. Biopsy of the mass revealed high grade undifferentiated pleomorphic neoplasm composed of atypical cells with hyperchromatic nuclei and scattered atypical mitotic figures (Fig. 3). An immunochemical stain was positive for smooth muscle actin and desmin. Stain was negative for S-100, cytokeratin AE1/AE3, myogenin, and Myo D1.
A follow-up positron emission tomography (PET) scan showed residual disease activity in the pulmonary veins. Patient was started on chemotherapy with ifosfamide and doxorubicin and was referred to a higher center for additional management. Patient has received four cycles of chemotherapy so far and one dose of radiation treatment. At 9-month follow up, the patient is doing well without any complications. | heart failure, heart neoplasms, left-sided heart failure, primary cardiac sarcoma | CT scan without contrast showing right pleural effusion and right hilar adenopathy with suggestion of node or mass with size of 3.2x2.2 cm. |
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PMC9705967_02 | Male | 0 | The infant suffered from chronic renal function damage; this was first characterized by elevated serum levels of creatinine (Scr) since day 3 after birth, with an estimated glomerular filtration rate (eGFR) of 5.2 ml/min/1.73 m2. Gradually, the serum levels of Scr and blood urea nitrogen (BUN) exceeded standard levels. According to the Guidelines for Chronic Kidney Disease (CKD) in Children, he suffered from stage 5 CKD at birth, which then improved to stage 3 from 9 months (with eGFR 34.2 ml/min/1.73 m2) to 1.5 years (with eGFR 36.5 ml/min/1.73 m2). His liver function tests were abnormal, including increased total bilirubin (TBIL, 131.2 micromol/L; reference range: 5.4-22 micromol/L), direct bilirubin (DBIL, 22.2 micromol/L; reference range: 0.4-6.2 micromol/L), glutamyl transpeptidase (GGT, 598 U/L; reference range: 9-150 U/L), and alkaline phosphatase (ALP, 324 U/L; reference range: 20-281 U/L) on day 3 after birth. Elevated levels of alanine transaminase (ALT, 61 U/L; reference range: 0-41 U/L), aspartate aminotransferase (AST, 86 U/L; reference range: 0-38 U/L), total bile acid (TBA, 109 micromol/L; reference range: 0-12 micromol/L), and phosphorus (P, 3.22 mmol/L; reference range: 1.6-3.1 mmol/L) were evident when he was 1 month old. Elevated levels of triglycerides (TG, 2.21 mmol/L; reference range: 0.7-1.7 mmol/L) were evident when he was 3 months old. Elevated levels of cholesterol (CHoL, 8.88 mmol/L; reference range: <=5.17 mmol/L) were also evident at 6 months of age. The levels of TBIL and DBIL returned to normal 2 months after birth; however, other indicators continued to be abnormal. There was no metabolic acidosis. Additional testing included blood routine tests, TORCH, viral hepatitis tests, autoantibody tests, and plasma amino acids, and the urine organic acid profile was normal (Table 1).
Abdominal ultrasound revealed bilateral hypodysplastic kidneys (Figure 2). The liver and biliary systems appeared normal. Cardiac ultrasound, cranial magnetic resonance imaging (MRI), spinal MRI, and eye examination (including fundus and slit lamp examination) revealed no obvious abnormalities.
Target genes were captured with the Clinical 4000 Pathogenic Gene Package (Guangzhou Jia-Jian Medical Testing, Guangzhou, China), which includes 4,047 genes associated with known Mendelian genetic diseases and genes for typical renal abnormalities like HNF1B and other renal ciliopathies and is based on the OMIM database (https://omim.org/). We identified a heterozygous variation in intron 33 of the NOTCH2 gene (c.5930-2A > G) but no variants of the JAG1 gene or any other variants of interest. The family members of the patient were also tested for the target variation by Sanger sequencing. His parents did not carry this mutation, suggesting that this was a de novo mutation. His parents had none of the clinical abnormalities seen in the baby. Transcriptomic sequencing was used to verify the splice site change at the RNA level caused by the variant, thus confirming that the c.5930-2A > G variant could lead to the skipping of exon 33, thereby leading to alterations in NOTCH2 mRNA splicing (Figure 3).
Next, we performed whole exome sequencing (WES) to analyze the coding exons and the exon-intron boundaries of protein-coding genes (Cipher Gene, Beijing, China), which included a special focus on genes affecting renal abnormalities. However, in addition to the c.5930-2A > G mutation in NOTCH2, no other genetic mutations were detected that matched the patient's phenotype.
In conclusion, ALGS was diagnosed by considering the results of molecular diagnosis, clinical features, ultrasound, and other auxiliary examinations. | alagille syndrome, notch2 gene, case report, congenitally bilateral renal hypodysplasia, prenatal oligohydramnios | Not supported with pagination yet | null |
PMC4735459_01 | Female | 24 | A 24-year-old African-American female college student with no significant past medical history presented to the emergency room with fever, lower abdominal pain and nausea without vomiting starting the day prior to admission. She noted that her menstrual period was slightly late, but otherwise the history obtained was non-contributory.
In the ED, she was found to be febrile (102 F) and tachycardic. She had an episode of vaginal bleeding while being evaluated. As a result, a pelvic examination was performed, which was unremarkable aside from scant blood in the vaginal canal and a closed cervix. Beta-HCG was obtained and was elevated at 784. Ultrasound of the abdomen and pelvis demonstrated a fetal sac in the uterus, but was otherwise within normal limits. Routine diagnostic testing was notable for a normal white blood count, normal hemoglobin, low platelets (92,000), normal kidney function (Cr 0.6), mild transaminitis (ALT 84, AST 72) and an indirect hyperbilirubinemia (TB 1.4, DB 0.3). Urinalysis demonstrated 5-6 WBCs, 9-10 RBCs, 10-12 epithelial cells, 1+ bacteria and trace leukocytes.
She was subsequently admitted to the medical service with the diagnosis of UTI and threatened abortion and was started on nitrofurantoin and IV fluids. Overnight, she spiked a high fever (104 F) with rigors. Morning laboratory investigations revealed a new leukopenia (WBC 2.8) and worsening thrombocytopenia (Plt 66,000). As a result, OB/Gyn was consulted for concern for possible septic abortion. They determined that it was an inevitable abortion and antibiotics were broadened. Given her worsening septic picture, infectious disease was consulted, a peripheral blood smear sent and doxycycline started for concern of ehrlichiosis. During the infectious disease evaluation, it is discovered that both the patient and her husband had recently traveled to Nigeria, her husband had been infected with malaria during their visit there, and she herself had developed a fever a day prior to returning to the USA and had become so ill en route that she presented to the emergency room directly from the airport.
Subsequently, the peripheral smear was reviewed by the ID attending in the laboratory and intracellular 'ear muff' shaped parasites consistent with Plasmodium falciparum were seen. As a result, the patient was diagnosed with uncomplicated malaria given no evidence of complications meeting criteria for severe malaria (namely, severe anemia, renal failure, ARDS, and hyperparasitemia). The CDC was contacted with respect to Artemisinin-based combination treatment. However, the decision was made to treat immediately with atovaquone/proguanil given that it was more readily available from an outside pharmacy than waiting for Artemisinin-based medication sent directly from the CDC. It was not until the third day of hospitalization that she received appropriate treatment. With anti-malarials, her clinical condition improved and she defervesced over the next 48 h. She was eventually discharged home after a six-day admission.
We conducted a retrospective case series of all patients with confirmed diagnosis of malaria from 2001 to 2012 at four Connecticut teaching hospitals (Waterbury Hospital, St. Mary's Hospital, Hospital of St. Raphael, & Griffin Hospital) in order to describe the demographics of imported malaria and to identify potential barriers to timely diagnosis and treatment.
Of a total of the fourteen patients, 54% were African, 23% American, 16% South Asian and 8% Hispanic. Most patients were foreign residents visiting the USA (54%), while the rest were USA citizens. A vast majority of patients were traveling in sub-Saharan Africa (73%, 9% India, 9% Pakistan, 9% Dominican Republic). Only a minority of patients took anti-malarial prophylaxis (22%). Symptoms began on average 3.1 days (range 1-8, SD 2.8) after arrival to the USA and patients presented to a healthcare provider on average 4.7 days (range 0-37, SD 12.1) after onset of symptoms. At the time of presentation, malaria was on the differential diagnosis in only half of cases and travel history was documented in only 69% of cases. Mean time to diagnosis was 2.9 days (range 0-12, SD 3.6). The vast majority of cases were due to P. falciparum (92%), while the remaining case was due to Plasmodium vivax. In general, parasite burden was low with 75% of cases with <=2% parasitemia.
Appropriate treatment was initiated in 93% of cases and mean time to treatment from time of presentation was 3.0 days (range 0-12, SD 3.6). Anti-malarial medications were available in the hospital pharmacy for only half of the cases. For these patients, treatment was administered promptly (mean 2.2 h, range 1-3 h). In cases where medications were not available in the hospital, there was a significant time delay between when the drug was ordered and when it was administered with 75% of patients receiving treatment >=8 h (mean 10.3 h, range 7-12 h) after it was ordered. In general, patients responded well to treatment. 71% were admitted to the hospital and only one case required ICU admission. Patients requiring inpatient admission were hospitalized on average for 3.2 days (range 1-7, SD 1.9). | connecticut, malaria, plasmodium falciparum | Not supported with pagination yet | null |
PMC8627139_01 | Male | 16 | Patient information: a 16-year-old boy who was a student, was admitted to the medical unit of the Buea regional Hospital after he presented with a two week history of gradually worsening shortness of breath and abdominal distension, non-productive cough, loss of appetite and weight loss. These became associated with fever three days prior to admission. There were no night sweats, and no sputum. There was no history of trauma.
Clinical findings: on physical examination, his temperature was 36.7 C, respiratory rate was 24 breaths/minute, heart rate 98/minute; blood pressure 87/71mmHg. Cardiovascular examination was remarkable for distended neck veins, hepatojugular reflux and pulsus paradoxus. There was no lower extremity edema. The heart sounds were not muffled. There was no pericardial friction rub. Lung examination revealed bilateral pleural effusions. Abdominal examination revealed ascites and a tender hepatomegaly. There were neither lymphadenopathies nor palpable masses to suggest malignancy.
Diagnostic assessment: the chest x-ray showed an enlarged cardiac silhouette with bilateral pleural effusions. The HIV test was negative. The C-reactive protein was 24mg/l, erythrocyte sedimentation rate equal 45mm. Echocardiogram showed a large circumferential pericardial effusion with right ventricular diastolic collapse and marked variation in tricuspid and mitral inflow suggestive of cardiac tamponade (Figure 1). Echocardiographic guided pericardiocentesis was performed through the sub-xiphoid route and about 500cc of hemorrhagic fluid was drained which improved his symptoms. Fluid analysis was consistent with an exudative effusion. Acid fast bacilli stain was negative. Extensive evaluation of the etiology was not performed because of limited resources in this rural hospital. A strong suspicion of tuberculosis was made and a presumptive treatment for hemorrhagic tuberculous pericarditis was started.
Therapeutic intervention: pericardiocentesis was performed and the patient was placed on anti-tuberculosis medications.
Follow-up and outcomes: a follow-up echocardiography after two weeks did not show re-accumulation of the pericardial fluid (Figure 2). Clinically, the dyspnea had regressed. There were no signs of right sided heart failure and no signs of cardiac tamponade. He has no adverse effects from the medications.
Patient perspective: during the time he was hospitalized and after the treatment, the patient and his family were delighted with the care he received and was optimistic about the outcome of his condition.
Informed consent: the patient and the family were informed about the case report, why the case was peculiar and the authors' interest in publishing his case. The family willingly gave informed consent to allow the authors to use his echo images for this case report.
Patient's consent: informed consent was obtained from the family for us to use the echo images and to publish the case. | pericardial effusion, cardiac tamponade, case report, tuberculosis | Not supported with pagination yet | null |
PMC2700576_01 | Male | 33 | A 33-year-old male, working in a grocery store presented to emergency room with a history of generalized weakness and breathlessness of class II over a period of two days. There was no history of fever, chest pain, palpitation, syncope or any known allergic disorders. He was a teetotaler and was not under any medications. His medical history otherwise was not significant. On examination, he was found to be conscious, well oriented, moderately built, and well nourished. There was no pallor, pedal edema or any clinical evidence of hypo or hyperthyroidism. He had a pulse rate of 48/min (irregular), BP: 80/60mm of Hg, and respiratory rate of 13/min. He was afebrile and his oxygen saturation on room air was 98%. Auscultation revealed normal heart sounds, no murmur or gallop but his heartbeat was regularly irregular. The lungs were clear. His abdomen and central nervous examinations were normal.
A provisional diagnosis of fatigue for evaluation was made. His capillary blood glucose level was 146 mg/dl and ECG showed bradycardia with Mobitz II block. Since there was symptomatic bradycardia, a trial of 2 mg of atropine was given intravenously and there was no response. He was started on dopamine 5 microgram/kg/min titrated upwards to 10 microgram/kg/min. He was admitted to the intensive care unit for further management. His hematological and biochemical values including thyroid profile, calcium, magnesium, and electrolytes were within normal limits. His Troponin-T, RPR [Rapid Plasma Reagin] test, and HIV status were negative. As he had isolated electrocardiographic features of Mobitz type II block without any demonstrable cause, he was subjected for echocardiogram, which was normal. The cardiologist opined for urgent pacing, but the patient refused. However, with the consent of the patient, his right internal jugular vein was canulated with 14G venflon so as to facilitate emergency transvenous insertion of pacemaker.
He was managed with oral orciprenaline and atropine (sos). Dopamine was slowly tapered and stopped within 36 hours. As the patient was symptomatically improving, a diagnosis of idiopathic second-degree type II A V block was considered. While on re-evaluation of the case, a non-specific penile ulcer was noticed. On careful interrogation, the patient admitted of suffering from penile ulcer for which he applied a native medicine paste on alternative days for a week as advised by a native medical practitioner of his village. The last application of the medication was 24 hours before presenting to our emergency room. He denied any extramarital relationship. Hence, the native medical practitioner was contacted in person to know more about the paste.
On interaction with the native physician concerned, he explained that the paste was made of bark and leaves of yellow oleander plant, tulsi, tamarind, onion, and neem. He also admitted that he was treating all open wounds or ulcers presented to him with the same paste! With the benefit of doubt, the patient was started with multidose activated charcoal (MDAC) for a day. So, the final diagnosis at the time of discharge was drug induced A V block probably due to transcutaneous absorption of oleander. Our diagnosis was supported by normalization of rhythm within 2 days in the absence of offending drugs.
As this has raised the suspicion of transcutaneous absorption of naturally occurring cardiac glycoside (oleander), it was decided to contact the native practitioner and find out if any of his cutaneous ulcer cases were on treatment with similar paste at present. Three more cases with cutaneous ulcer on treatment with similar paste were evaluated at the practitioner's clinic, after obtaining informed consent as all of them refused hospitalization and modern medicines. They were followed up at their residence. | oleander leaf extract, reversible cardiac conduction disorder, transcutaneous absorption | Not supported with pagination yet | null |
PMC2909719_01 | Male | 34 | A 34-year-old man was referred to the Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand from the Department of Medicine, King Chulalongkorn Memorial Hospital with a chief complaint of a painful and burning sensation of lip and oral mucosa when consuming food. The patient was an ex-intravenous drug user who had acquired HIV and hepatitis C (HCV) genotype 1 infections for 12 years possibly from multiple heterosexual partners or intravenous drug use. He had tuberculosis (TB) of lymph gland and had been treated with anti-TB drugs for one year. Six months after the TB treatment, HAART was started with daily doses of 600 mg AZT, 300 mg 3TC, and 800 mg of EFV. Monitoring of drug efficacy was assessed periodically. Baseline plasma HIV-1 RNA viral load (VL) was 97,500 copies per mL (4.99 log) before commencing HAART. He responded quite well to the treatment and the HIV-VL fell below the limit of detection of less than 50 copies per mL after 6 months of treatment. The patient's immune status was improved with the absolute CD4+ T cell count at baseline, 6 months, and 30 months as 31, 168, and 287 cells per muL, respectively.
The patient denied drug hypersensitivity, smoking, and alcohol consuming habits. The oral lesions developed two and a half years after beginning HAART. Oral examination revealed erosive lesions of the lip and right and left sides of buccal mucosa. The lesions had slightly raised keratotic white reticular striae and white papules on an extensive background of erythematous mucosa with deep ulcerations (Figures 2(a), 2(b), and 2(c)). Clinical scores of the right and left buccal mucosa as well as the lip lesions were 5, 5, and 4, respectively. Both lateral sides of the tongue displayed nonpainful and very mild white plaques. Areas of redness corresponding to the sharp edges of the adjacent teeth were also observed. The OLDR diagnosis of lesions at the lip and buccal mucosa was based on the history of medications and the incidence of initial eruptions of the lesions as shown in Figure 1. Management in this patient was focused on relieving the symptoms. Topical fluocinolone acetonide 0.1% orabase, solution, and sodium bicarbonate mouthwash were prescribed. Smoothing of sharp edges area of teeth resolved in healing of the red area at lateral sides of the tongue, and long-term follow-up was planned. While the use of topical steroid relieved the patient of oral pain, the lesions themselves did not resolve. After treating the oral lesions for 19 months, a liver biopsy was performed and showed fibrosis stage 3 from chronic HCV type 1 hepatitis. Pegylated interferon and ribavirin were planned to be prescribed to the patient in management of the HCV infection. Due to the myelosuppressive effect of AZT, it was decided to withdraw the patient from AZT prior to interferon administration. AZT was switched to tenofovir (TDF) 300 mg, but EFV and 3TC were continued. Two months after the withdrawal of AZT and with the local topical steroid treatment, only very mild white papules at right buccal mucosa remained, and the clinical pain score at this site was 1, while other sites were in complete remission (Figure 3). Pegylated interferon and ribavirin therapy began 1 year after the cessation of AZT. | null | Not supported with pagination yet | null |
PMC8794752_01 | Male | 31 | A 31-year-old man with a non-smoking history was diagnosed with asthma along with paroxysmal cough, sputum, dyspnea, and wheezing. His asthma was well controlled with inhaled corticosteroid/long-acting beta2-agonist (budesonide formoterol, 1,280 microg/36 microg/day), long-acting muscarinic antagonist (tiotropium, 2.5 microg/day), and leukotriene receptor antagonist (montelukast, 10 mg/day). Three years after the diagnosis of asthma, his cough, sputum, and dyspnea worsened, with a high blood eosinophil count of 1,222/mul. Administration of oral prednisolone (20 mg/day) for 1 week temporarily improved his respiratory symptoms. However, the symptoms recurred after cessation.
He was therefore hospitalized with these respiratory symptoms. On admission, he had fever (38.1 C) and hypoxia (SpO2: 93% at room air). Laboratory tests revealed elevated levels of blood eosinophil count (1,976/microl), total IgE (529 IU/ml), and fractional exhaled nitric oxide (FeNO; 165 ppb). Myeloperoxidase-anti-neutrophil cytoplasmic antibodies and fungus-specific IgE antibodies (Aspergillus, Candida, and Alternaria) were negative (Table 1). Pulmonary function test results showed mild obstructive ventilatory impairment with a percent forced expiratory volume in one second of 73%. Asthma Control Test (ACT) score is 15. Reverse transcription-polymerase chain reaction assay of the sputum specimen for the presence of severe acute respiratory syndrome coronavirus 2 showed a negative result. HRCT findings showed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs (Figure 1A).
Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs (Figure 2A). The fraction of eosinophils in BAL fluid increased to 67%. The culture of the bronchoalveolar lavage specimen was positive for Moraxella catarrhalis and negative for Mycobacterium tuberculosis and fungi. Hematoxylin and eosin staining of the mucus plug section showed a multilayered structure with accumulation of many chromatolytic eosinophils (Figure 2B). On immunofluorescence staining of identical section, there was deposition of major basic protein (MBP) over a wide area. Galectin-10-positive Charcot-Leyden crystals (CLCs) were formed near the MBP-deposited area with net-like DNA (Figure 2C). These immunostaining findings suggested that the deposition of granule proteins and the formation of CLCs proceeded because of the cytolytic process of eosinophils.
Based on these clinical findings, the possibility of eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary mycosis (ABPM), and eosinophilic pneumonia was excluded. The diagnosis of eosinophilic bronchiolitis was established based on the reported diagnostic criteria. Ceftriaxone (2 g/day) and oral prednisolone (30 mg/day) were initiated. After 4 days of treatment with these drugs, the respiratory symptoms with fever and hypoxia disappeared. His blood eosinophil count decreased to 165/mul after 14 days of treatment.
When the dose of oral prednisolone was tapered to 15 mg/day 3 months after disease onset, his respiratory symptoms worsened. HRCT showed bronchial wall thickening and centrilobular nodules, as seen during diagnosis (Figure 1B), suggesting recurrence of the disease. The dose of oral prednisolone was increased to 20 mg/day. Given the long-term adverse events due to systemic corticosteroids, benralizumab, an anti-IL-5Ralpha antibody, was added. After 14 days of its initiation, the blood eosinophil count decreased to 0/mul, and his respiratory symptoms improved. ACT score improved to 16. Radiological findings of bronchial wall thickening and centrilobular nodules also attenuated (Figure 1C). The dose of oral prednisolone was tapered to 15 mg/day without relapse. | charcot-leyden crystal, etosis, benralizumab, eosinophil, eosinophilic bronchiolitis, mucus plug | Radiological findings. (A) High-resolution computed tomography (HRCT) findings on admission showing bronchial wall thickening and centrilobular nodules in the lower lobe of both lungs. |
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PMC8119778_01 | Male | 65 | A 65-year-old male farmer presented to our hospital with complaints of nausea, vomiting, chest tightness, and chest pain in March 2020. Three hours prior to presentation, the patient consumed 400 mL of chlorpyrifos in an attempt to commit suicide. Then, he presented with nausea, vomiting, sweating, and muscle tremors accompanied by slight chest tightness and pain. After he was found by his family, the patient was immediately sent to a local community hospital where gastric lavage was carried out and 10 mg of atropine was intravenously injected. However, the symptoms were not resolved, and his chest pain worsened. For further treatment, he was transferred to our hospital. His medical history included hypertension for 20 years and coronary heart disease for half a year. Six months ago, the patient underwent percutaneous coronary intervention (PCI), during which, a stent was implanted in the left anterior descending coronary artery. He consumed alcohol occasionally and had a 20-year history of smoking and smoked 40 cigarettes per day.
On physical examination, the patient was restless. His axillary temperature was 36.9 C, blood pressure was 145/100 mmHg, heart rate was 105 beats/min (bpm), and respiratory rate was 20 breaths/min. The diameters of both pupils were 4 mm. His heartbeat was fast and regular, without a murmur, and his upper abdomen was mildly tender. The skeletal muscle of the extremities went into spasm, with an increased muscle tone. The lungs were clear, and the neurologic examination was unremarkable.
In the coagulation analysis, the international normalized ratio was 1.52, and the D-dimer level was 1.044 mug/mL. Cholinesterase level was 498 U/L, NT-pro BNP was 3,667.4 pg/mL, cardiac troponin I was 1.005 ng/mL, creatine kinase was 526 U/L, creatine kinase isoenzyme-MB was 34 U/L, alpha-hydroxybutyric dehydrogenase was 220 U/L, and lactate dehydrogenase was 282 U/L. Levels of electrolytes, as well as tests for liver and renal function, were within normal limits. As shown in Figure 1A, an electrocardiogram taken at the local community hospital showed a symmetrical negative T wave in leads V1-V6 and an upsloping ST-segment at the J point continuing into positive symmetrical T waves in leads II, III, and aVF. Chest radiography and abdominal ultrasound revealed no obvious abnormalities.
Based on the above clinical manifestations, medical history, result of auxiliary examinations, and level of serum biomarkers, the patient was conclusively diagnosed with an acute non-ST-segment elevation MI, severe chlorpyrifos poisoning, and grade 1 hypertension (very-high-risk group).
After admission to the cardiac care unit, the patient received oxygen by nasal cannula. Because the patient and his family refused coronary intervention, pharmacologic treatment was provided instead. For AMI, the patient was orally administered with 180 mg of ticagrelor, 0.3 g of aspirin, 10 mg of rosuvastatin calcium, and 25 mg of metoprolol tartrate. For hypertension, oral valsartan (40 mg) in the form of dispersible tablets was given. For chlorpyrifos poisoning, he was treated using an intravenous injection of 2 g of pralidoxime iodide for the revitalization of cholinesterase. Additionally, parenteral nutrition support and 40 mg of pantoprazole sodium injection for rehydration, maintenance of nutrition, and protection of gastric mucosa were provided. On the following day, his chest pain diminished. However, he reported an obvious upper abdominal pain, accompanied by tarry stools. Considering that the bedside abdominal ultrasound revealed none of the clinically significant findings, he was treated with 8 mg of norepinephrine tartrate injection and 2 g of oral sucralfate tablets to control the gastrointestinal bleeding and protect the gastric mucosa. As shown in Figure 2, his heart rate dropped to 79 bpm after taking metoprolol tartrate tablets. A low dose of atropine and metoprolol tartrate was simultaneously adjusted to maintain the heart rate to <90 bpm. At night, he developed a fever of 38.6 C. A routine blood test revealed that his WBC count was 6,200 per cubic millimeter, with 73.9% of neutrophils, 14.1% of lymphocytes, and 12.0% of monocytes. His hemoglobin level was 12.8 g/dL. The patient was treated with an injection of 0.9 g of lysine acetylsalicylate and 3 g of cefoperazone sodium.
On day 4 of admission, his abdominal pain eased. Re-examination of the electrocardiogram revealed a normal sinus rhythm and the T-wave inversion in leads V1-V4 disappeared, without a pathological Q wave (Figure 1B). The patient was allowed to consume some liquid food, and the infusion volume was reduced. On day 5 of admission, cholinesterase levels rose from 498 to 4,476 U/L (Figure 3A), and cardiac troponin I decreased from 1.005 to 0.134 ng/mL (Figure 3B). Due to economic reasons, the patient and his family expressed a strong desire to be sent home for further rehabilitation. He continued taking aspirin, ticagrelor, and rosuvastatin after discharge. When followed-up on August 26, 2020, his condition was stable, and delayed encephalopathy was not observed. | acute myocardial infarction, antiplatelet agents, atropine, chlorpyrifos poisoning, treatment strategy | Not supported with pagination yet | null |
PMC4308088_03 | Male | 63 | Patient 3 is a 63-year-old right-handed man, formerly a professional footballer, who was referred to our epilepsy clinic with a history of left hippocampal sclerosis, which was surgically resected 15 years earlier. Although seizure frequency decreased as a result, the patient's epilepsy remained quite refractory to treatment with four AEDs. Although some seizures would occur from sleep, the patient identified physical exertion as another clear precipitant. This was fairly reproducible, and seizure control improved dramatically when he avoided any vigorous exercise. Gentle walking was not associated with any issues. Retrospectively, the patient felt that exercise had been a part of the pattern for years, even prior to his surgery. Interestingly, in addition to his typical seizures, exercise could induce a bout of severe depressive feelings. He also found that there was a family history of depressive symptoms provoked by exercise. On review by a neuropsychiatrist, it was felt that these latter symptoms actually represented part of a postictal psychosis, and some improvement was made with the introduction of olanzapine. | cortical localization, exercise, reflex epilepsy, seizure triggers | Not supported with pagination yet | null |
PMC4308088_04 | Female | 48 | Patient 4 is a 48-year-old right-handed woman with temporal lobe epilepsy with bitemporal independent seizures documented on video-EEG monitoring. Events followed an encephalitic illness of unclear etiology several years prior and were resistant to polytherapy with four AEDs, with seizures occurring at least weekly. The patient noted that they were much more likely to occur while playing her weekly game of netball in the evenings. | cortical localization, exercise, reflex epilepsy, seizure triggers | Not supported with pagination yet | null |
PMC4646473_01 | Female | 38 | The patient was a 38-year-old female, housewife, who was admitted on discovery of a splenic mass during a routine physical examination. She had no complaints of abdominal bloating, abdominal pain, cough, expectoration, weight loss, incompetent, etc. She had no family history of tuberculosis (TB) or contact with patients with TB. She had no history of steroid intake. An abdominal ultrasound showed several hypoechoic masses in the patient's spleen. Magnetic resonance imaging (MRI) indicated splenomegaly and multiple irregular intrasplenic masses without clear boundaries. Inhomogeneity was shown inside the masses, where T2-weighted images showed mainly high intensity signal, and low intensity signal was seen in the periphery around some of the masses. T1-weighted images showed mainly equal intensity, and slight hyperintensity was seen inside and around some of the masses. With a contrast-enhanced scan, no enhancement of the masses was seen, whereas the boundaries became clearer rendering a honeycomb appearance (Figure 1). Other significant laboratory tests included white blood cells of 4.8x109/L, erythrocyte sedimentation rate of 30 mm/h, C-reactive protein of 8 mg/L, human immunodeficiency virus test was negative, normal chest X-ray, and a normal electrocardiogram. A decision was made to remove the spleen. During the surgery, the spleen was found to be enlarged with tense adhesions to the surrounding tissues and a significant amount of small tubercles on the surface of the left diaphragm, upper-left abdominal peritoneum, stomach, gastrosplenic ligament, splenic fossa, and the nearby greater omentum. A large amount of suppuration and curdled material was seen when the spleen was open. Since TB was not on our list of differential diagnoses initially, only intravenous levofloxacin was given for 1 week after surgery and the patient was discharged. Postoperative pathology showed intrasplenic granulation accompanied by necrosis, and negative acid-fast staining (Figure 2). Twenty days after the surgery, the intraoperative pus culture demonstrated positive bacillus growth. The patient had not received any anti-TB medications at this point.
The patient developed a fever 2 months after surgery. Physical examination showed a temperature of 38 C, headache, no obvious nausea or vomiting, no loss of consciousness, and no myoclonus. MRI indicates a 4.0x3.3 cm mass in the right frontal lobe. The right ventricle was deformed with a left midline shift. No changes were observed in the other ventricles and cisterna. The diagnosis from the MRI was intracranial abscess (Figure 3). Lung computed tomography (CT) suggested multiple pulmonary nodular lesion and pulmonary cavitation (Figure 4). A complete blood count showed a white blood cell count of 10.6x109/L, platelet count of 792x109/L, and C-reactive protein of 11.0 mg/L. Cerebrospinal fluid analysis showed chloride of 128 mmol/L, glucose of 3.3 mmol/L, and proteins of 1.13 g/L. The diagnosis of a TB intracranial abscess and pulmonary TB after splenectomy for a TB abscess was made, and the HRZE (isoniazid 300 mg qd, rifampin 450 mg qd, pyrazinamide 500 mg tid, and ethambutol 750 mg qd) regimen was started immediately. Twenty days later, chest CT indicated a significant shrinkage of the pulmonary loci, and the patient's head MRI showed a slight decrease in the size of the intracranial abscess. Anti-TB regimen was discontinued 1.5 years later. Regular follow-up showed a complete resolution.
This case report was approved by the ethics committee of The First Affiliated Hospital, School of Medicine, Zhejiang University, and the patient provided their agreement and written consent to this report being published. | antituberculosis treatment, cerebral abscesses, diagnosis, lung tuberculosis, postoperative, solitary splenic tuberculosis | and pulmonary cavitation . Abbreviation: CT, computed tomography. |
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PMC9499727_01 | Male | 0 | A 10-day-old male presented with high-grade fever and jaundice for six days and seizures for two days. On examination, the baby was febrile, irritable, icteric, and hepatomegaly without eschar, rash, or petechiae. The abdomen was distended. The axillary temperature was 39.3 C, the pulse rate was 176/min, and the respiration rate was 46/min. A complete blood count showed that the white blood cells (WBCs) count was 24.76x109/L with 76.4% lymphocytes, 12.1% neutrophils, and 8.1% monocytes. Tests showed that the total bilirubin level was 87.4 micromol/L, aspartate aminotransferase level was 336.6 U/L, alanine aminotransferase level was 1317.1 U/L, and lactate dehydrogenase level was 1477.6 U/L. Cerebrospinal fluid (CSF) examination showed a WBC count at 283x106/L with 95.1% mononuclear cells, 4.9% polymorphonuclear neutrophils, a protein concentration of 3.084 g/L and a glucose concentration of 1.18 mmol/L. Computed tomography (CT) showed patchy low-density areas in the bilateral frontal, temporal, and parietal lobes (Figure 1A). Tests for malaria, dengue, toxoplasmosis, leptospirosis, mycobacterium tuberculosis, rubella, cytomegalovirus, herpes simplex virus, and Japanese encephalitis virus were negative. A diagnosis of neonatal bacterial meningitis was made, and the patient was started on cefotaxime sodium combined with ampicillin and phenobarbital to control fever and seizures. On the third day of admission, his seizures and jaundice had subsided, but the fever persisted, and the CSF still showed abnormalities. We re-evaluated the family history and found that the patient's mother had anemia (Hb: 73 g/L) since the 28th week of pregnancy and reversed fever of unknown origin from three days before delivery to postpartum. On examination, there was an 1.2x0.8 cm eschar on her left groin (Figure 1B). The Weil-Felix test was positive for OXK 1:640 and 1:160 in the mother and baby, respectively, and both had positive IgM-ELISA 1:160 to the Karp antigen. Meanwhile, Metagenomic next-generation sequencing (mNGS) was positive for Orientia tsutsugamushi in both mother and baby (Supplementary Material). The final diagnosis of the baby was congenital infection of scrub typhus with bacterial meningitis. His treatment was immediately adjusted to intravenous azithromycin 10 mg/kg/day for three weeks and oral azithromycin for one week, and his mother was treated with oral tetracycline. After treatment, the baby and his mother's condition improved and stabilized. During the 4 weeks of hospitalization, the EEG, MRI, psychomotor assessment and Griffiths assessment were normal. No neurological sequelae were found after 6 months of follow-up. Written informed consent was obtained from the child's parents. | orientia tsutsugamushi, congenital infection, meningitis, neonatal scrub typhus, vertical transmission | Not supported with pagination yet | null |
PMC10026180_08 | Male | 5 | This patient was a 1.5-year-old boy of Arab ethnicity, born to healthy non-consanguineous parents, and has one healthy older sister.
From early infancy, the patient experienced failure to thrive, had milk allergy with bloody stools, lymphadenopathy, and splenomegaly.
Elevated immunoglobulins, T and B cell numbers were normal (4,821 and 3,304 cells/mm3, respectively); test result of Bacillus Calmette-Gueri (BCG) vaccine-positive (The patient had axillary lymphadenopathy, which was positive to BCG.). There was altered neutrophil function as determined by using the DHR test.
A hemizygote CYBB (GP91) stop codon mutation (c.388C > T, p. Arg130Ter) was found.
Chronic granulomatous disease (CGD) X-linked, BCGitis.
TMP-SMZ, itraconazole, tuberculosis (BCGitis)-triple antibiotic therapy with isoniazid, rifampin, and ethambutol.
At 10 months of age, the patient presented with erythematous papules and nodules on the buttocks, which spread to the inguinal areas and his back (Figure 8A). In addition, he had an erythematous purulent nodule in the left inguinal region and bilateral lymphadenopathy. The clinical differential diagnosis included inflammatory conditions (granulomas, sarcoidosis) or an atypical infection (mycobacterial, fungal, or viral).
Skin biopsy:(1) suppurative dermatitis with scale crust and epidermal micro-abscess formation. Periodic acid- Schiff (PAS), Giemsa (GMZ), Ziehl- Neelsen (ZN), and HSV stains were negative. (2) Consistent with MCV. PCR test result was positive for MCV.
Culture of pus drained from a left inguinal abscess grew Klebsiella pneumonia.
An ultrasound of the inguinal area was notable for left inguinal phlegmon with hyperemic lymph nodes up to 20 mm.
The patient was treated with weekly cidofovir (5 mg/kg) for 4 weeks, IV vancomycin and piperacillin-tazobactam, and topical antibiotics with good response (Figure 8B).
CGD is characterized by the absence or malfunction of the Nicotine adenine dinucleotide phosphate (NADPH) oxidase in phagocytic cells. CGD patients suffer from recurrent, life-threatening bacterial and fungal infections. There are limited reports of severe viral diseases such as those reported by us in this series. Bone marrow stem cell transplantation is currently the only curative treatment. | cutaneous, immunological aspects, inborn error of immunity, infection, pediatric, primary immunodeficiencies | Not supported with pagination yet | null |
PMC5838870_01 | Female | 30 | A 30-year-old obese (BMI 35.3) female was struck by a tow truck and dragged for 30 ft. Initial trauma evaluation revealed a left sided closed femur fracture, treated with intramedullary (IM) nailing, and a humerus fracture with open reduction internal fixation (ORIF). Additional radiologic findings included a small bowel mesenteric hematoma, managed non-operatively, a small left flank hematoma, and six-rib fractures. The burn service was consulted on hospital day 5 for management of her abdominal friction burns (TBSA 13%), of which 4% appeared to be full thickness on initial evaluation [Fig. 1]. The patient was taken to the operating room (OR) for an uncomplicated tangential excision and allografting of the abdominal friction burn. Upon return to the OR 5 days later for planned excision of allograft and placement of autograft, significant progression of burn depth and adipose necrosis was noted and the left flank was distended and edematous. Upon further excision of necrotic adipose tissue, the underlying fascial-cutaneous separation (MLL) was discovered, and approximately 1.5 L of serosanguinous fluid was evacuated from this cavity [Fig. 2]. To prevent re-accumulation of fluid into this dead space, a 19F round Blake drain was placed in the dependent portion of the MLL, the overlying cutaneous defect was grafted with a 2:1 meshed split-thickness skin autograft, a negative pressure dressing was used to bolster the graft, and an abdominal binder was worn at all times. During the first 24 and 48 post-operative hours, 700 and 1055 mL of serosanginous fluid were drained, respectively. The primary dressings were removed 5 days post-autografting with satisfactory results [Fig. 3]; after 5 weeks, autograft take was noted to be > 95% with further aesthetic improvements appreciated [Fig. 4]. | blunt trauma friction burns, friction burns, internal degloving injuries, morel-lavallee lesion, traumatic pseudocyst | Not supported with pagination yet | null |
PMC8414571_01 | Male | 3 | The proband was born in 2007, weighing 2,600 g with 49 cm in length after a gestation period of 39 weeks. The patient was weak and susceptible to illness as a child. A heart murmur was detected in the patient at a local hospital at the age of 1. For further treatment, his family requested hospitalization when he was 3 years old. After examination, he was diagnosed with HHS (patent ductus arteriosus, persistent left superior vena cava, and congenital absence of left arm radius) (Figures 1A, 2A). PDA ligation under general anesthesia was performed in the patient, and the procedure was successful (Figure 1B). After obtaining consent from the patient's parents, we recruited their blood and inquired about their family and previous medical history (Figure 3A). In addition, craniofacial dysmorphisms were observed in the patient. Ten years later, we visited the patient and inquired about his physical and study conditions in detail. At the time of the visit, the patient was 152 cm tall, weighed 42 kg, and was able to communicate normally. His grades were between 20 and 40 in all subjects (total score 100-120/subject), near the bottom of his class. According to the latest version of "the height and weight percentile table of Chinese people aged 0-18 years" released by the Capital Pediatric Research Institute, the height and weight of the proband were lower than 90 and 80% of the same age group (13.5 years old), respectively. Mild intellectual disability (IQ 59) was detected using the Wechsler Intelligence Scale. An imbalance of the dorsal muscles was observed (Figure 2B). Combined with sequencing results, we concluded that the proband had BAF-opathies.
Given that the patient's clinical diagnosis was heart-hand syndrome, we screened the TBX5, SALL4, and LMNA genes, but no deleterious variation was found. Subsequently, targeted sequencing, including a panel of genes associated with congenital heart disease, was performed on the patient.
Whole-exome sequencing was conducted to generate 12.4 GB data with 99% coverage and a depth of >100 x in this patient. After data filtration, a novel heterozygous variant of ACTL6A (NM_004301, c.478_478delT; p.F160Lfs*9) was identified. This variant led to frameshift sequences and a premature termination codon, potentially affecting the features of the resulting proteins. According to the nonsense-mediated mRNA decay theory, this variant may induce the decay of ACTL6A mRNA in patients. Bioinformatics analysis predicted that this variant was deleterious.
Sanger sequencing was performed to validate this variant (Figure 3B). Cosegregation analysis showed that this is a de novo variant and does not exist in the 1,000 Genome Browser, ExAC Browser, Exome Variant Server, gnomAD browser, or 200 unrelated ethnically matched healthy controls. The amino acid sequence was highly conserved (Figure 3C). There is a large distinction between the standard and mutant protein models constructed with SWISS-MODEL, which may affect the assembly of the BAF complex (Figure 3D). | actl6a, baf-opathies, ssridds, craniofacial dysmorphisms, heart-hand syndromes, intellectual disability | Not supported with pagination yet | null |
PMC4971151_01 | Male | 35 | LCVA, 35 yr-old, gave birth in November 24th, 2015 of a male neonate with 3500 g, cephalic perimeter of 34.0 cm and with normal vital signs at Hospital Alianca, a 210 bed tertiary hospital in Salvador, Brazil. Antenatal visits were normal except for reporting that four days before a C-section delivery she experienced a disseminated rash and fever with dengue serology positive for IgG and negative for IgM.
The neonate was doing well until November 28th when the newborn developed a macular erythematous rash, hypoactivity and temperature of 37.9 C. On November 30th, the neonate began presenting generalized seizures that responded to anticonvulsants.
Blood, saliva, urine, and CSF samples were screened for CHIKV, Zika, and Dengue using rt-PCR techniques. Briefly, RNA was extracted using QIAmp Viral RNA mini kit according to manufacturers instructions for CHIKV. The amplification product was 305 bp within the gene that codes for the viral envelope protein E2 of CHIKV. For Zika virus, the amplicon product was 192 bp within the gene that codes for the viral NS5 region. HSV was screened in CSF and Acyclovir was initiated. EEG showed diffuse slowing compatible with the diagnosis of encephalitis.
Brain NMR showed hyperintensity signals on diffusion-weighted imaging (DWI) involving the subcortical white matter of the frontal, parietal, temporal areas, and the corpus callosum as shown in Figs. 1-3 , and were unremarkable in T1 or T2 weighted images with no enhancement in post-contrast T1-weighted NMR imaging (Fig. 4).
NMR imaging of the brain showing no enhancement of the lesions.
CSF results: 0.7 mononuclear cells per mm3, protein 106 mg/dL; glucose 23 mg/dl; immune markers for syphilis (Fta-Abs, VDRL) and toxoplasmosis (indirect immunofluorescence assay) were negative; and aerobic, mycobacterial and fungal cultures were all negative. Rt-PCR for CHIKV was positive in CSF, blood, urine and saliva. Rt-PCR for Zika virus, Dengue virus, and HSV were all negative.
The newborn began to show improvement in neurological parameters, being more active, from December 9th and was discharged home on December 16th. The newborn was more active, less hypotonic, and showing a normal sucking and palmar grasp reflexes.
Geraldin et cols presented cases of CHIKV encephalopathy with a similar pattern of neurological involvement as seen in our case and indicative of an early cytotoxic edema with marked reduction of the apparent diffusion coefficient.
In La Reunion Island CHIKV outbreak during 2005-2006, cases of chikungunya-associated encephalitis contributed to a two-fold increase in the regional overall incidence of all encephalitis.
During an outbreak in India 3 fatal cases in children were documented and were associated with nervous system complications. In the La Reunion epidemic, a similar report of 3 deaths were documented in children under 18 years, and 2 of them were due to encephalitis.
The pathogenic mechanism of the various neurological syndromes during CHIKV infection is largely unknown. Neurological involvement in CHIKV infection may include encephalitis, meningoencephalitis, encephalomyeloradiculitis, among others. | chikungunya neonatal, chikungunya-associated encephalitis, neonatal encephalitis, neurological syndromes, vertical transmission | Not supported with pagination yet | null |
PMC9380730_01 | Female | 87 | An 87-year-old female with R-R long intervals due to atrial fibrillation admitted to our hospital. On Day +15, she underwent leadless pacemaker implantation ("on Day +X" means that "on Day X after admission"). She received regular infection prevention treatment both preoperatively and postoperatively. On Day +16, she developed an unexplained low-grade fever without cough or sputum. She also had night sweats. Blood counts indicated slightly elevated neutrophil, C-reactive protein (CRP), and interleukin-6 (IL-6) levels. The T-SPOT test repeatedly suggested elevated levels of antigen A and antigen B. Additionally, her blood sedimentation level was significantly elevated, fluctuating between 60 mm/h and 70 mm/h.
On Day +23, she received regular anti-infective therapy with a specific regimen of cefoperazone-sulbactam 3 g/8 h. On Day +42, she underwent chest ultrasonography, which suggested that the amount of pleural fluid had increased compared to the previous amount. At this point, we considered regular anti-infection treatment ineffective. On Day +46, she underwent thoracentesis and drainage. We sent her pleural fluid for testing, and the results suggested that her pleural fluid/serum protein was >0.5. Therefore, we considered the pleural effusion to be exudate. Considering that the patient was an elderly woman, the patient's family refused to undergo pleural biopsy.
On Day +57, she received diagnostic anti-tuberculosis treatment. The specific regimen was isoniazid 0.3 g/d, rifapentine 0.9 g/week, pyrazinamide 0.25 g/8 h, levofloxacin 0.5 g/d, and methylprednisolone 40 mg/d. Additionally, she underwent a computer tomography (CT) scan of the chest, as shown in Figure 1A. We observed a moderate amount of liquid density shadow in the chest cavity bilaterally, mainly on the right side, with a CT value of 5 HU. Chest CT also suggested that adjacent lung tissue was compressed. After diagnostic anti-tuberculosis treatment, her low-grade fever resolved, and pleural fluid decreased. Besides, she has a 20-year history of exposure to tuberculosis (TB) patients. Therefore, we made a clinical diagnosis of tuberculous pleurisy for this patient.
On Day +72, she underwent ultrasonography of the chest, which showed no fluid in the chest cavity bilaterally. On Day +74, her platelet dropped from 189*109/L to 43*109/L. We considered thrombocytopenia in relation to the use of isoniazid. Therefore, we temporarily stopped the anti-tuberculosis treatment. Her platelet levels returned to normal after stopping anti-tuberculosis treatment.
On Day +92, we added linezolid 600 mg/12 h and moxifloxacin 0.4g/d. After using linezolid and moxifloxacin, her symptoms were better than before. On Day +110, she reappeared with thrombocytopenia, and she received platelet transfusion therapy. We believed that the cause of this thrombocytopenia was related to the use of linezolid. Therefore, we adjusted the anti-tuberculosis regimen to cycloserine 0.25 g/d and contezolid 400 mg/d. During the follow-up treatment, her platelet count increased from 68*109/L to 324*109/L. She did not have any further adverse reactions. Therefore, we increased the drug doses of cycloserine and contezolid. On Day +121, we modified the drug dose to cycloserine 0.25 g/12 h and contezolid 400 mg/12 h. On Day +131, she underwent another chest CT examination, as shown in Figure 1B. This result indicated a significant reduction in bilateral pleural effusion compared with the image in Figure 1A. Her body temperature fluctuated within the normal range. Therefore, we considered the anti-tuberculosis treatment effective.
For the treatment of heart diseases, rivaroxaban 10 mg/d was used for the treatment of atrial fibrillation. She was bedridden for a long time. Her pacemaker function was normal prior to death. Therefore, heart diseases have little relationship with the death of this patient. We considered that she died of a pulmonary embolism on Day +136. Besides, Figure 2 shows the treatment of this patient. | contezolid, tuberculous pleurisy | Not supported with pagination yet | null |
PMC3198116_01 | Male | 65 | A 65 year old Caucasian male was admitted acutely complaining of generally feeling unwell with fever, painful skin swellings over his arms and legs, headache and epigastric pains.
He had a complex 4 years history when he presented with intermittent fever and chills, arthralgia of large joints, painful skin nodules of arms and legs, dry cough, shortness of breath, redness of his right eye, painful right testicle, anorexia and weight loss of two months duration. He denied oral or genital ulcers. Over the ensuing two months he was extensively investigated to define the underlying disease.
The main abnormalities on previous investigations were as follows:
Complete blood count: Hemoglobin 106 gram per litre, mean corpuscular volume (MCV) 97.5, erythrocyte sedimentation rate (ESR) 134 mm/Hr, C-reactive protein (CRP) 135 mg/dl (normal less than 3.5). Normal total white blood cell (WBC) count and differential. Rouleoux, oval macrocytes. Pseudo Pelger-Huet cells and occasional myelocytes on film. Platelet and reticulocyte counts were normal.
Liver function test: gamma-glutamyl transferase 172 (7-64 iu/l), alkaline phosphatase 399 (42-121 iu/l), albumin 16 (32-55 iu/l), bilirubin and alanine aminotransferase normal.
Urea 10.2 (3-6 mmol/l), creatinine137 (53-115 umol/l). Normal sodium and potassium.
Immunoglobulin (IG) G level was raised (polyclonal) 19.1 (8-18 gm/l). Normal IgM, IgA and IgE levels.
Chest X-ray: Bilateral patchy basal consolidation and mild bilateral pleural effusions which were confirmed on computerized tomographic scans.
Ultrasound scan of scrotal sac showed changes consistent with epididymo-orchitis.
CT scan of the abdomen: normal.
The following serological tests were done and found to be negative: Hepatitis B & C screen, HIV test, anti-nuclear antibodies, anti-DNA antibodies, rheumatoid factor, anti-cytoplasmic antibodies, anti-cardiolipin antibodies, Coomb's test, ASO titre, cryoglobulins, Brucella serology, complement levels, C1-esterase level.
Other negative tests done for a possible infective agent: malaria film, Brucella culture, Mantoux test, sputa for acid fast bacilli, leprosy nasal smears, urine microscopy.
Two skin biopsies were taken:
Sample 1: Summary of findings:
Skin showing extravasation of erythrocytes in the upper dermis. Deeper down there is a panniculitis, mainly of lobular type. The inflammation consists of histiocytic cells, lymphocytes, and granulocytes. There is a large vessel with thickened muscular wall containing granulocytes and lymphocytes. Picture of panniculitis with vasculitis.
Sample 2: Summary of findings:
Skin fragment shows rather normal epidermis. Upper dermis shows extravasation of erythrocytes. Capillary blood vessels show sometimes thickened walls, containing leukocytes. Picture consistent with leucocytoclastic vasculitis.
Other biopsies taken and found to be negative/normal were:
Bilateral temporal artery biopsies
Conjuctival biopsy
Liver biopsy
Bronchoscopy and bronchoscopic samples
Bone marrow aspirate/biopsy: Unsuccessful initial attempt. Patient declined a repeat.
The patient was empirically treated with broad spectrum antibiotics, anti-malarial therapy followed by treatment for tuberculosis and brucellosis, without improvement. Treatment with oral prednisolone 60 mg a day resulted in prompt improvement in his well-being, subsidence of his fever and normalization of his ESR.
Over the subsequent years, he was maintained on prednisolone therapy. However, it became apparent that reducing his prednisolone dose or non-compliance on the patient's part resulted in the prompt recurrence of his painful nodular skin lesions, fever, arthralgia, urticarial facial swellings, lung infiltrates (pneumonitis), and increase in both C-reactive protein and ESR (above 100 mm/hr). His general condition usually worsened during these episodes, resulting in frequent hospital admissions. Unfortunately, high dose prednisolone led to the development of diabetes mellitus which necessitated using oral hypoglycemic agents. A brief trial of azathioprine as a steroid-sparing agent worsened his anemia and it was discontinued.
Bone marrow examination at another hospital showed myelodysplasia but with no cytogenetic abnormalities.
Over the years, in addition to myelodysplasia, he was given various diagnoses including Behcet's disease, anti-phospholipid syndrome, and pyrexia of unknown origin responsive to steroids.
These included warfarin for two previous confirmed episodes of deep venous thrombosis (left leg and right leg), glibenclamide for diabetes mellitus and prednisolone 10 mg per day.
He looked ill and pale. He had an urticarial right peri-orbital swelling as well as several tender 0.5-1.0 cm subcutaneous nodules felt over the extensor and flexor surfaces of both upper and lower limbs. There was no lymph node enlargement and no oral, respiratory, cardiovascular, abdominal, neurological, musculoskeletal or genital abnormalities.
Hemoglobin 9.1, MCV 101.3, WBC 9.9, platelets 152, ESR 133, CRP 103, international normalized ratio (INR) 3.1.
Renal and liver function and urinalysis were normal.
Chest X-ray - normal.
Electrocardiogram - normal.
The patient was given intravenous hydrocortisone 100 mg three times a day with a quick resolution of his symptoms and disappearance of his painful skin swellings. Within few weeks his ESR dropped to 33 mm/hr. On reducing his steroid dose to 10 mg per day of prednisolone, his facial urticaria recurred and he developed a left sided pleuritic chest pain. A chest radiograph confirmed a new left basal infiltrate and an associated small effusion. These again promptly resolved (within 48 hours) on increasing his steroid dose. Cyclosporin was then added as a possible steroid-sparing agent.
A repeat bone marrow examination was performed.
Salient features of bone marrow aspirate: multilineage dysplasia involving the granulocytic, erythroid and megakaryocytic cell lines.
Erythroid dysplastic features including: increased mitosis, nuclear lobulation and extensive vacuolation.
Myeloid dysplastic features were found in at least 19% of the precursors. These features included pseudo Pelger-Huet anomaly, misshapen nuclei and increased vacuolation. Blasts made up about 2% of all nucleated cells. Normal amounts of stainable iron were present with normal numbers of sideroblasts. Pathologically ringed sideroblasts were not present.
Salient features of bone marrow core biopsy:
Pronounced hypercellularity (98-100%). The tri-lineage dysplasia was confirmed; the presence of micromegakaryocytes, the megalobastoid erythropoiesis and the presence of numerous mitotic figures. Especially noteworthy was the abnormal localization of immature myeloid precursors (ALIP). Lymphocytes and plasma cells were normal. Reticulin fibrosis was mildly increased and thinned-out bony trabeculae confirmed osteoporosis. Abnormal non-haemopoietic cells and/or granulomata were not present. | diagnosis, myelodysplastic syndrome, vasculitis | Not supported with pagination yet | null |
PMC5974685_01 | Female | 66 | A 66-year-old female presented with chief complaints of progressively worsening pain in the left ankle with inability to stand or walk, more so while walking over uneven surfaces for the past 8 months. On detailed history taking, no other specific positive points such as trauma, pain in other joints, or any constitutional symptoms were found. Clinical examination revealed diffuse tender horseshoe-shaped swelling all around subtalar joint with markedly restricted, painful subtalar joint movements. Her X-rays revealed a reduction of subtalar joint space with generalized osteoporosis (Fig. 1a and b). 20 and 40 Broden views also confirmed the presence of subtalar arthritis (Fig. 2a and b). All blood investigations including arthritic profile were within normal range. She was diagnosed as a case of seronegative type of subtalar joint arthritis. She underwent surgical intervention in the form of open subtalar joint arthrodesis with sinus tarsi approach. All, posterior, anterior, and medial facets of subtalar joints were prepared for sound fusion. Two 6.5 mm cannulated cancellous screws were used in compression mode for fixation. Screws were passed from non-weight bearing aspect of heel up to the neck of the talus. Additional anterior aspect of calcaneus was also used. This screw was 5.0 mm cannulated cancellous and was used with the purpose of sound fusion of middle and anterior subtalar joint (Fig. 3a and b). The patient being a case with severe osteoporosis, addition of proximal tibial bone grafts was done to augment fusion. Calcium and Vitamin D3 supplements were also added. Her post-operative course was uneventful. After removal of suture, a below knee plaster was applied for 4 weeks, and the patient was kept non-weight bearing. X-rays at 6 weeks post-surgery showed slow union (Fig. 4a-c). Teriparatide injections were added for enhancing union. X-rays at the end of 6 months did showed non-progressive and non-convincing progress of fusion (Fig. 5a-f). The patient was advised progressive weight bearing over 6 months. The patient always complained of persistence of swelling and pain on ambulation, which was treated with compression bandage and analgesics and anti-rheumatics.
The patient kept on coming back with complains of pain, difficulty in walking, and swelling in the foot without any other symptoms. Hematological investigations were repeated, which showed a rise of CRP (16 mm/L) and ESR (36 mm/h) with total leukocyte count being 12000. A course of intravenous broad-spectrum antibiotics (1.5 grams of cefoperazone andsulbactam twice a day plus 750 mg of amikacin once a day) was given for 3 weeks followed by 1 week of oral a ntibiotics (linezolid 600 mg twice a day) presuming a presence of low-grade infection. MRI could not be done because of the presence of stainless steel implants. Computed tomography scan at 8 months post-surgery showed the persistence of erosion and joint space at fusion site (Fig. 6a-c). Considering this as a case of non-union plus infection, it was decided to go for two staged surgical interventions, where first stage was planned as removal of implants and debridement and the second stage as revision fusion after a course of antibiotics. At second surgery through the same approach, implants were removed. Fusion was found to be incomplete. No pus discharge was noticed. Dirty granulation tissues were scrapped from the fusion site, and material was sent for histopathology examination. Postoperatively, the patient was immobilized in anterior and posterior below knee plaster splints. The same broad-spectrum intravenous antibiotics were continued. Histopathologic examination showed epithelioid granulomas with plenty of giant cells suggestive of tuberculosis (Fig. 7a and b). This was of a great surprise as the patient had no previous history of tuberculosis or any constitutive symptoms such as fever, night-pains, weight loss, or loss of appetite. The samples were reviewed at two other laboratories which also confirmed the diagnosis of tuberculosis. Antituberculosis treatment was started and the patient was given rest in the same below knee splint for 6 more weeks. Plan was to do revision fusion after 6 weeks under cover of antituberculous drugs. Serology showed improvement and so was patient. X-rays showed signs of fusion, and hence, surgery was delayed (Fig. 8a and b). Spontaneous fusion was noticed just with antituberculous medicines, and at the end of 3 months, fusion got completed and the patient was walking full weight bearing without any complaints (Fig. 9a-f). | subtalar joint, antituberculous treatment, fusion | Not supported with pagination yet | null |
PMC3439939_01 | Male | 49 | A 49-year-old male presented for evaluation of recurrent vitritis, floaters, and decreased vision of the right eye over the preceding year. Past ocular history was significant for laser assisted in situ keratomileusis (LASIK) of both eyes (OU) 7 years before. Past medical history was notable for carpal tunnel surgery 20 years ago, a right ankle fracture decades ago, and an episode of abdominal shingles several years ago. He had a questionable diagnosis of rheumatoid arthritis due to right knee swelling and distal phalangeal joint disease. He had a history of right ankle swelling and scarring and had undergone two arthroscopies of his right ankle 4-6 years prior to presentation. There was no family history of ocular or autoimmune disease. He did not smoke, drank alcohol occasionally, and did not use illicit drugs. He had extensive travel history outside the US including to the Middle East, Europe, and Asia when he was in the military.
Examination demonstrated best corrected visual acuity of 20/50 OD and 20/20 OS. Pupillary exam and intraocular pressures were normal. Slit-lamp examination OD showed 1+ conjunctival injection, stromal scarring at the LASIK flap interface, 2+ cells in the anterior chamber, and pigment along with some white deposits on the anterior lens surface (Figure 1). His left eye exam was normal. Dilated fundus examination OD revealed vitreous debris but no retinal vasculitis or other chorioretinal lesions (Figure 1). Fluorescein angiography was unremarkable. He was diagnosed with anterior and intermediate uveitis OD and a systemic workup was initiated. Rapid plasma regain (RPR), angiotensin-converting enzyme (ACE), and HLA-B27 were negative, erythrocyte sedimentation rate (ESR) was elevated at 46, and a chest X-ray showed sequela of old granulomatous disease. Polymerase chain reaction (PCR) testing on aqueous fluid for herpes simplex virus (HSV) and varicella zoster virus (VZV) was negative.
Despite treatment with topical, oral, and periocular corticosteroids OD, inflammation persisted and whitish, fluffy endothelial deposits near the limbus in both eyes and an infiltrating "snowflake-like" crystalline keratopathy at the level of the endothelium OD were observed (Figure 2). Injection of intravitreal vancomycin and ceftazidime was performed given the suspicion of infection and aqueous fluid was cultured for bacteria, fungus, acid fast bacilli and PCR testing was performed for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and VZV. In vitro response of aqueous fluid to mycobacterium tuberculosis was indeterminate and all remaining tests were negative. Further serological testing revealed negative antibodies for Toxoplasma, Leptospira, Hepatitis A, B, and C. EBV serology demonstrated evidence of past infection. Serum protein electrophoresis was unremarkable. A QuantiFERON gold test for mycobacterium tuberculosis was negative. A diagnostic and therapeutic vitrectomy was performed and testing of vitreous for Borrelia burgdorferi PCR and cytology was unrevealing. After cessation of corticosteroid treatment, the crystalline keratopathy (Figure 3) faded and intraocular inflammation resolved. Subsequent cataract surgery OD was performed without complication.
Concurrent with his ocular inflammation, he was evaluated for decreased appetite, intermittent abdominal pain, and a 20-pound weight loss. Computed tomography (CT) of the abdomen and pelvis showed diffuse mild fatty infiltrates of the liver and borderline cardiomegaly. Lab work showed leukocytosis, which was felt to be reactive, iron deficiency anemia, and low folate levels. C-reactive protein (6.25) and ESR (34) were both elevated. He underwent genetic testing for hematological disorders and flow cytometry which were both unremarkable. He was started on iron and folate supplementation. He underwent upper GI endoscopy which showed a small sliding hiatal hernia and a colonoscopy which showed internal hemorrhoids. He underwent an upper GI biopsy demonstrated Barrett's esophagus. Thyroid testing and a cosyntropin stimulation test for adrenal insufficiency were normal.
Excisional biopsy was performed for an enlarged nontender right inguinal lymph node. Flow cytometry of the lymph node demonstrated a monoclonal population of lambda-restricted B cells with an immunophenotype consistent with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. However, hematoxylin and eosin (H&E) sections of the lymph node did not show effacement of architecture and immunohistochemical stains did not detect sheets of B cells, characteristics usually present in CLL. These findings were suspicious but not diagnostic for CLL/small lymphocytic lymphoma. Histopathology also demonstrated scattered and grouped macrophages with periodic acid-Schiff- (PAS-) positive inclusions suggestive of Tropheryma whipplei infection.
He developed worsening dyspnea due to decompensated valvular heart disease with biventricular heart failure. Echocardiography confirmed severe aortic regurgitation with mild left ventricular enlargement and an ejection fraction of 50%. Left heart catheterization showed no obstructive coronary disease. He underwent aortic valve replacement with a bi-leaflet mechanical valve. Intraoperatively, diffuse pericarditis was noted.
He was started on high-dose trimethoprim-sulfamethoxazole for presumed Whipple's disease. A CT of the abdomen and pelvis was obtained which showed retroperitoneal pelvic inguinal adenopathy. The lymph node and aortic valve pathology blocks were sent to the Centers for Disease Control (CDC, Atlanta, Georgia) for review, and the presence of T. whipplei was confirmed by PCR, immunohistochemistry (immunoalkaline phosphatase technique), and PAS staining that showed PAS-positive diastase-resistant organisms within macrophages (Figure 2).
Despite initial improvement in appetite and weight gain, he gradually developed an aortic perivalvular leak and severe aortic insufficiency thought to be secondary to possible re-infection of the mechanical valve. He underwent another aortic valve replacement, ascending aortic replacement, and a 2-vessel coronary artery bypass. The prosthetic valve was sent to the CDC and also showed evidence of T. whipplei infection by PCR, PAS, and immunohistochemistry stains. He developed complete heart block and ultimately expired due to cardiogenic shock and cardiac arrest 2 years after his initial presentation for decreased vision. | null | Not supported with pagination yet | null |
PMC4438594_01 | Female | 0 | About 20, 3-month-old female, Sprague-Dawley rats were obtained from Charles River. The protocol pertaining to all procedures and aspects of the study was approved by the University of Alberta animal care and ethics committee. Before arrival, to induce an osteoporosis (OP)-like increase in bone resorption, ten rats were ovariectomized (OP-OVX); the remaining ten rats were sham-operated as normal controls (OP-Sham). All rats were euthanized 12 weeks after OVX and/or sham surgery and lumbar vertebrae 4-6 (L4-L6) were dissected. The muscle and soft tissues connected to vertebrae were removed, and samples were wrapped in paper towels dampened with phosphate buffered saline and stored frozen at -30 C for subsequent Micro-CT scan.
The excised vertebrae, L4, L5, and L6, were thawed at room temperature for 2 h before scanning. All vertebrae were imaged using a benchtop Micro-CT imager (SkyScan 1076; Bruker-MicroCT, Kontich, Belgium) at 18 mum voxel image resolution with 70 kV, 100 muA, and a 1.0 mm aluminum filter. Projection images were reconstructed using bundled vendor software (Nrecon 1.6.1.5; Bruker-MicroCT, Kontich, Belgium). Dataviewer 1.4.3 software was employed to orient the cross sectional images parallel to the transaxial plane. A cylindrical region of interest (ROI) was segmented from trabecular bone within the vertebral body. The diameter of each cylinder was constrained by the endocortical bone margin enclosing the vertebra. The vertebral growth plates at each end were used to landmark the top and bottom segmentation boundaries. We utilized CTAn 1.11.6.0 (Bruker-MicroCT, Kontich, Belgium) to morphometrically analyze the trabecular bone cylinder. In order to calibrate BMD with Hounsfield units (HU), two hydroxyapatite [Ca10(PO4)6(OH)2] phantoms (Computerized Imaging Reference Systems Inc., Norfolk, VA, USA) with BMD 0.250 and 0.750 g/cm3 were included in the calculation based on the assumption that HUair = -1000 and HUwater = 0. The threshold, 70 ~ 255, was chosen to segment out bone on 8-bit (0 ~ 255 gray level) bitmap (BMP) images. The measured structural parameters were BV/TV, BMD, Tb.Th, Tb.Sp, FD, Tb.Pf, DA, and Conn.Dn. Those parameters were calculated three dimensionally (3D) based on the volume of the cylinder. Except for Conn.Dn, all structure parameters were also calculated two dimensionally (2D) from cross sectional images slice by slice, along the longitudinal direction from caudal to cranial (Figure 1), and graphed with respect to the normalized height of the cylinder. The results were compared between groups and different levels of vertebrae in the same group.
The results of the Micro-CT structural parameters indicated that the largest difference between groups were in the 40% portion of the cylindrical length from the caudal side. Thus, it was selected for FEA (Figure 1). The cross sectional images of this region were imported into Mimics 14.11 (Materialise, Leuven, Belgium) to build finite element meshes. Since the voxel of the Micro-CT data was 18 mum ( 17.156 mum), that dimension was used to build voxel mesh (hexahedral elements) for FEA to maintain the details of the microarchitecture. To avoid losing or distorting microarchitecture of trabecule, no resizing or smoothing was undertaken prior to meshing. After creating hexahedral elements (hex8), the meshes were exported as an input file (*.inp) format of ABAQUS (SIMULIA, Providence, RI, USA). The remaining pre-processing to include material properties and boundary conditions were done in ABAQUS/CAE 6.10-1. Since bone is expected to behave elastically and failure expected with small strain, the analysis was set as linear and elastic with Young's modulus (E) = 24.5 GPa and Poisson's ratio (nu) = 0.3. All vertebrae were assigned with the same material property, as no significant difference of material properties was measured between normal and OVX bone. The bottom of the cylinder was fixed and a displacement (Deltad), 5% of the height of the cylinder (strain = 0.05), was applied to the top of the cylinder. The stiffness (k) of the bone was calculated by dividing the summation of the vertical reaction forces (R) on the fixation to the applied displacement. Since the sizes of individual vertebrae varied, the stiffness (which comprises information of geometry and material property) would also vary with size. Therefore, values of k were further normalized with the theoretical stiffness (k'), which was calculated from the size of each cylinder by assuming that the cylinder was solid (Figure 2). The index of bone stiffness was represented as k/k'.
PASW Statistics 17.0 was used for statistical evaluations. The two-independent-samples test, Mann-Whitney U test, was used to find differences between individual groups on the same level of vertebra. This method was applied to both the results of Micro-CT structure parameters and the stiffness calculated by the FEA. The difference among three levels (L4, 5, and 6) of the same group was tested by Kruskal-Wallis H test. The Mann-Whitney U test was done to understand the difference between two individual vertebral levels. Results were shown as mean +- SD. An asymptotic value (p-value) <0.05 was used to evaluate the significance of differences. The correlation between Micro-CT structural parameters and the index of stiffness was described with Pearson correlation coefficients (r). The significance level was set at 0.05 (Sig. <0.05) with the two tailed test. | bone stiffness, finite element analysis, micro-computed tomography, microstructural parameters | Not supported with pagination yet | null |
PMC6512746_01 | Female | 65 | A 65-year-old woman was diagnosed as a neurosarcoidosis and oral administration of prednisolone (PSL) 45 mg/day was started. Methotrexate (MTX) 8 mg/week was added 4 months after PSL administration. A month later, she complained of fever and productive cough. A chest computed tomography (CT) revealed an abnormal shadow in the right upper lobe of the lung and right pleural effusion. She was treated with oral levofloxacin, but her symptoms and abnormal chest shadow did not improve. She was referred to our hospital for further examination and treatment.
Vital signs were stable and no abnormality was noted in physical examination. Laboratory testing revealed a white blood cell count of 6,670 per mm3, erythrocyte sedimentation rate of 30mm/1h, C-reactive protein of 1.2mg/dl, immunoglobulin (Ig) G of 622 mg/dl. beta-D glucan and KL-6 were within normal limits. Chest radiograph showed infiltrative shadows in the upper right lobe and right pleural effusion. Chest CT revealed right dominant non-segmental infiltrative shadows, multiple nodules, and right pleural effusion (Fig. 1a). Although we suspected the possibility of MTX-induced interstitial lung disease and discontinued this treatment, her symptoms and chest radiograph became worse.
Considering the immunocompromised host and radiological OP pattern such as non-segmental infiltrative shadows, we had to differentiate between idiopathic, collagen diseases, infection, malignant tumors, and drug reaction as causes of OP, and therefore performed a bronchoscopy obtaining a transbronchial lung biopsy (TBLB) of the right S2 region. The biopsy specimens revealed diffuse lymphocytes in the alveolar wall, and some of the alveolar spaces contained Masson bodies, which was consistent with OP. Moreover, intra-alveolar granulomas and high fibrin precipitation and bleeding, which strongly indicated various degrees of inflammation, were revealed (Fig. 1b). Spherical fungi of large variation sizes of about several mum to 20 mum were revealed by Grocott's silver stain (Fig. 1c). According to the finding of Grocott's silver stain, we considered the possibility of Cryptococcus neoformans or Pneumocystis jirovecii. Mucicarmine staining, which stains the yeast capsule of Cryptococcus red, was negative. However, the tissue specimens also lacked the characteristic of Pneumocystis jirovecii such as size uniformity of 4-10 mum, crescent-shaped, helmet-shaped, and intracystic dots. In the culture test of bronchial wash, general bacteria, acid-fast bacteria and fungi were all negative. Furthermore, the serum cryptococcal antigen was positive. It is known that there is the capsule-deficient form of cryptococcus, which is negative of mucicarmine staining. Finally, we diagnosed her as secondary pulmonary cryptococcosis. After fluconazole treatment, her symptoms, chest radiograph and CT finding improved (Fig. 1d). | bronchoscopy, cryptococcosis, immunocompromised host, organizing pneumonia, serum cryptococcal antigen test | Not supported with pagination yet | null |
PMC9091407_01 | Male | 16 | A 16-year-old male adolescent presented with low back pain with progressive protrusion of the lumbar spinous process 3 years before the first visit. The protrusion in his back was not noticed from his neonatal period to early childhood by his parents, until it was discovered around the age of 13 years. After playing basketball caused his lower back pain to worsen, he visited a nearby clinic and was found to have an abnormality in the L2 vertebral body. The patient was then referred to our department. He had no medical history, including congenital diseases or spinal trauma. His chief complaint was lower back pain, which was exacerbated by exercise. He was 173 cm tall and weighed 60 kg at his first visit. The spinous process protruded in the upper lumbar spine, with tenderness in the bilateral paravertebral muscles at the same level. Neither symptoms in the lower extremities nor abnormal neurological findings were observed. The Japanese Orthopaedic Association (JOA) score for lumbar spinal disorders was 27 points out of 29.
The anteroposterior (AP) radiogram of the whole spine revealed no obvious scoliosis, with bone maturity of Risser Grade 4 (Fig. 1a). The lateral radiogram of the whole spine showed hypoplasia of the anterior portion of the L2 vertebral body with a sagittal vertical axis (SVA) of -60 mm (Fig. 1b). The AP diameters measured at the center of the L1, L2, and L3 vertebral bodies were 36 mm, 27 mm, and 41 mm, respectively. The spinal parameters measured in the lateral radiogram were as follows: Thoracic kyphosis (TK) at T5-12, 17 ; local kyphosis at L1-3, 23 ; lumbar lordosis (LL) at L1-S1, 38 ; LL at L3-S1, 59 ; and pelvic incidence (PI), 34 (Fig. 1b). In the dynamic lateral radiograms, local kyphosis at L1-3 was 23 in the extended position (Fig. 2a) and 44 in the flexed position (Fig. 2b). In addition, the facet joints at the L2-3 spinal level were subluxated in the flexed position (Fig. 2b). Computed tomography showed symmetrical hypoplasia of the anterior portion of the vertebral body of L2 (Fig. 3). Based on these radiological findings, the patient was diagnosed with L1-3 local kyphosis, with anterior column hypoplasia and subluxation of the facet joints at L2-3.
Spine-shortening osteotomy at L2 and L1-3 posterior fusion was performed for local stabilization and correction of the sagittal malalignment, using a pedicle screw and rod system with compression laminar hooks, as reported previously. This procedure is equivalent to Grade-4 osteotomy by anterior column realignment classification. First, the laminae and transverse processes of the L1-3 vertebrae were exposed. Polyaxial pedicle screws were placed bilaterally at the L1 and L3 vertebrae, parallel to each upper endplate (EXPEDIUM VERSE System , DePuy Synthes, Raynham, MA). The lower half of the L1 lamina, the L1-2 facet joints, and the upper half of the L2 lamina were resected using a high-speed burr and chisels. Then, the upper half of the L2 pedicles was removed using a high-speed burr. Subsequently, a wedge-shaped osteotomy of the upper part of the L2 vertebral body was performed together with the removal of the L1-2 intervertebral disc. The wedge-shaped osteotomy was performed with the preoperatively designed osteotomy line, with the starting point at 8 mm caudal from the posterosuperior edge of the L2 vertebral body, cutting up toward the anterosuperior endplate at an angle of 30 to the lower endplate of L1 to set local kyphosis between L1 and L3 to 0 after correction. For correction, the screws were converted from polyaxial to monoaxial screws by semi-locking the set screws. After placing bilateral temporary rods on the screws, the posterior portions of the L1 and L3 vertebral bodies were compressed gradually using a hook system (DYNACORE , Mizuho Corporation, Tokyo, Japan). The alignment and bone-on-bone contact were confirmed by fluoroscopy and the screws were connected to the final rods. Finally, autologous local bone pieces from the posterior vertebral elements were grafted between L1 and L3.
A whole-spine AP radiogram at 2-year post-operative follow-up revealed no obvious scoliosis (Fig. 4a). The lateral radiogram demonstrated that SVA improved to 9 mm, TK to 35 , local kyphosis at L1-3 to -2 , LL to 40 , and LL at L3-S1 to 34 (Fig. 4b). In addition, bone union was confirmed at L1-2 vertebral bodies by computed tomography (Fig. 4c). His lower back pain was completely relieved and his JOA score showed a maximum 29 points. Two years postoperatively, the patient had no symptoms, bony fusion was completed, and no correction loss was detected. | anterior column hypoplasia, congenital, developmental, kyphosis | Not supported with pagination yet | null |
PMC4247868_01 | Female | 78 | We here report a case of a 78 year old woman, with free medical history, who presented to the Emergency Department of our Hospital with erythema nodosum on her both shins (Figure 1A). She also mentioned low grade fever since 15 days and a positive family history of tuberculosis (daughter). Her chest X-Ray revealed bilateralhilar lymphadenopathy, mainly at the right side (Figure 1C). Further evaluation with High Resolution chest Computed Tomography confirmed the lymphadenopathy and demonstrated ground-glass opacities. The Mantoux skin test was strongly positive (22 mm) (Figure 1B). Anti-TB treatment was started, based on the positive Mantoux test, the compatible imaging findings and mainly, the history of close and direct exposure. Sputum cultures proved to be positive for Mycobacterium tuberculosis. Patient's response to treatment was impressive and in her follow up visits, she remained free of symptoms and a define improvement of her imaging findings was observed. | erythema nodosum, hilar lymphadenopathy, tuberculosis | Not supported with pagination yet | null |
PMC6852003_03 | Female | 46 | Most of the participants had been admitted to locked wards for varying periods. Admissions to locked wards were described as very difficult, especially if patients were put into seclusion. A 46-year-old single woman, with a bachelor's degree in arts, who was secluded during a manic episode, described it as follows:
'It is hell. Life can be hell. Life can be hell. At times you feel: God are you still there, are you still there ...' (Int. 19, [translated from Afrikaans])
An elderly lady, in her second marriage for 29 years and a Grade 10 qualification, was immediately admitted to a locked ward following an outburst of anger:
I
'What had happened when you broke the window of the psychologist?'
P
'He carried on about my son's death [due to suicide] and the more I said, I do not know, the more he said, but I should know. When he repeated that again, I became furious; I initially wanted to hit him, but I then broke the window. Then they locked me up.' (Int. 9, [translated from Afrikaans]) | containment, psychiatric hospital, psychiatric inpatients, psychiatry registrar training, therapeutic relationships | Not supported with pagination yet | null |
PMC6852003_06 | Male | 32 | Having recovered from a psychotic episode, the 32-year-old single man already quoted above, talked about the importance of being treated as a fellow human being:
I
'I found it interesting that you said these trainee nurses that came in treated you as equals, as not someone who is sick, but just as a fellow human being.'
P
'Yes ... as trainees they were more like people who were not exposed so much to this kind of environment. ... [they were] able to blend with us and not look at us as patients, but look at us as fellow human beings, because they were able to learn from us as well and we were able to learn from them. And they were able to take the knowledge that they got from us and utilise it to better their careers, I think.'
I
'It sounds as if they approached you in a very open way, not with preconceived or preformed ideas.'
P
'Exactly.'
I
'And that was very meaningful and helpful.'
P
'In a big way ... in a big way. It really meant a lot to me because they were not judging us, yeah ... they were there asking us questions like normal people, not like people who are mentally ill or something like that, but normal people. ... They respected us.' (Int. 5)
The same patient valued being able to teach a staff member something; it valued him as a human being:
'I even taught one male nurse basketball. There was a basketball here, so I'm a very big fan of basketball and I play basketball a lot. So, I even taught that one guy how to score and he managed to be able to learn from me and he said to me, he's going to try and practice as he goes home; whenever he gets a ball he's going to keep on practicing. So, for me it was an eye opener that somebody can take something like that from me, it was good to ... it was more like a highlight as well.' (Int. 5)
Building a personal, therapeutic relationship will take time. The same patient is again quoted, describing the lack of therapeutic relationships with registrars - if someone really wants to know a patient, he or she must be a psychologist according to the patient:
P
'They [the registrars] lack certain things ...'
I
'Like what?'
P
'... With the doctors, they don't have enough time ... some patients they have a lot of stories to tell, or they need to be asked certain questions ... the time that is given probably is small ... and that would be not enough for some people. I guess that I think, that is lacking to the doctors. I think ... whatever the doctors are trained for, they're quick in doing things, like as I'm talking to you right now, I'm open, I'm speaking to you, and to me you sound like a psychologist, somebody who wants to know me, like, more.' (Int. 5) | containment, psychiatric hospital, psychiatric inpatients, psychiatry registrar training, therapeutic relationships | Not supported with pagination yet | null |
PMC10405622_01 | Male | 67 | This 67-year-old Caucasian male developed progressive pancytopenias and was referred to our institution in August 2007. The patient's bone marrow aspirate revealed 43% blasts with the morphology and an immunophenotype consistent with acute myeloid leukemia (AML), M4 according to the French-American-British (FAB) classification (see Fig. 1 A, B). Cytogenetic and molecular tests showed a normal diploid karyotype, and the FLT3 mutation status was negative. His other significant past medical history included seronegative rheumatoid arthritis, and a history of prostate cancer, treated with radical prostatectomy. The patient's AML initially was treated with 2 courses of clofarabine between August and October of 2007. However, he was found to be primary refractory to this treatment with persistent bone marrow blasts, accounting for 14% of the marrow cellularity in November 2007. Therefore, the patient then received salvage treatment with 3 courses of idarubicin, cytarabine, and XIAP antisense (AEG-53156) between November 2007 and February 2008, and again he was found to have persistent AML cells, accounting for about 7% of the marrow cells in bone marrow specimens from March and May of 2008. The patient therefore proceeded to a double cord blood stem cell transplantation (CB-SCT) in June 2008 after nonmyeloablative conditioning with fludarabine (40 mg/m2/day x 4) plus cyclophosphamide (50 mg/kg x 1), antithymocyte globulin (ATG), and total body irradiation (TBI) (2 Gy). He received supportive red blood cell and platelet transfusions in the peri-transplantation period as well as filgrastim. The patient did not suffer any significant infectious complications after the transplantation. One month after the transplantation a bone marrow biopsy with PCR-based microsatellite polymorphism analysis showed 100% host chimerism, indicating graft failure. However, despite the failure to engraft, the patient achieved a complete remission with clearance of marrow blasts by morphology and flow cytometry, and subsequent normalization of his peripheral counts. Fig. 1 C and D show bone marrow aspirate smears after CB-SCT that are consistent with a complete remission and depict scattered large granular lymphocytes.
About 6-7 weeks after the CB-SCT, the patient gradually developed a lymphocytosis that is illustrated in Fig. 2A. The lymphocytes were 100% of host origin by microsatellite polymorphism analysis, and they were oligoclonal CD8+ T-cells, as demonstrated by the oligoclonal pattern of T-cell receptor gamma chain gene rearrangements by PCR analysis, and flow cytometry, respectively. Fig. 2B illustrates the immunophenotype of the expanded T cells. Now sixteen months after his cord blood transplant, the patient has been without any evidence of leukemia both on peripheral blood and bone marrow tests, and has been managed only with observation. Clinically, the patients has become fully asymptomatic and doing very well over the course of the last year, and his arthritis, which was a (possibly paraneoplastic) major clinical issue at diagnosis also is in remission.
The clinical course and the laboratory studies in this case suggest that the allogeneic cord blood cells triggered the oligoclonal expansion of autologous cytotoxic T cells that cross-react with the patient's AML clone. To our knowledge, this is the first case of a remission after an unsuccessful engraftment of CB-SCs, and therefore we will discuss these findings in the context of the graft-versus-leukemia (GvL) effect and spontaneous remission (SR) in AML.
SR is an infrequent but recurrent and often well-documented phenomenon in patients with renal cell carcinoma or malignant melanoma, but a rarity in cancers of the hematopoietic system. The published cases of spontaneous remission in patients with acute myeloid leukemia (AML) indicate that this is an exceedingly rare and generally temporary event, with a mean remission duration of approximately 6-7 months. The mechanism responsible for inducing these remissions is largely unknown, although the reported cases suggest that there may be a correlation with infections or blood transfusions. It has been speculated that these events trigger immune responses responsible for SR. Natural killer cells and cytotoxic T cells transfused with blood products, or cytokines such as tumor necrosis factor (TNF) and interleukin-2 (IL-2), released during infections have been proposed to participate in the development of SR. Previous reports of successful re-induction of a second SR by BCG vaccination support the hypothesis that SR in AML is a T-cell mediated process. In hematopoietic stem cell transplantation (SCT), the importance of T cell-mediated immune responses for induction of remissions via the "graft-versus-leukemia" (GVL) effect is well established. Furthermore, it is increasingly recognized that the induction of an effective allo-reactive T cell responses against leukemia stem and progenitor cells is essential for complete eradication of AML after SCT. Several studies have demonstrated a correlation between the presence of T cells recognizing leukemia CD34+ progenitor cells and the occurrence of complete remissions in vivo. Furthermore, distinct minor histocompatibility antigens (MiHA) expressed on AML progenitor cells, that are recognized by CD8+ T cells, are emerging, and have been proposed as target antigens for immunotherapy.
In summary, we report the fascinating case of a primary refractory AML patient that achieved a complete remission after an allogeneic SCT with graft failure, lasting now for over 16 months. This remission coincided with the oligoclonal expansion of autologous, CD8+ T cells, suggesting that the CB-SCT triggered the induction and expansion of autologous cytotoxic T cells that cross-react with the AML clone. This unique case illustrates that failure of a therapeutic intervention (here: the cord blood graft loss) can sometimes trigger events that benefit the patient, and also encourages our hopes that our immune system, if properly primed and targeted, has the capacity to overcome relapsed/refractory AML, clinically one of the most dismal settings. In Winston Churchill's words: "Success is not final, failure is not fatal: it is the courage to continue that counts". | null | Not supported with pagination yet | null |
PMC10120813_01 | Female | 39 | A 39-year-old woman, who is a sanitation worker, unmarried and nulliparous, was admitted to our hospital because of linear-erythema with accompanying pruritus and formication in her left upper arm for 1 month. The lesion appeared after she had cleared the grass in the highway greening zone. The linear erythema was misdiagnosed as eczema in her local hospitals. She also received a topical therapy with mometasone furoate cream to alleviate pruritus. One week before the admission, the skin lesion gradually spread to the proximal part of the upper limbs, and the intense pruritus severely affected her sleep, work, and quality of life. Hence, she came to our hospital. She denied hepatitis, tuberculosis, or other infectious diseases, and had no history of smoking, drinking, allergies, or surgery. On admission, dark red, linear, spiral patches were seen on the lateral side of the upper arm. The lesion was well-circumscribed with a slightly raised border, and no ulcerations or erosions (Figure 1A and B).
Laboratory testing showed completely normal humoral and cellular immune function. A blood test revealed a white blood cell count of 7.10 x 109/L (reference range: 4.0-10.0 x 109/L), eosinophil count of 1.3 x 109/L (reference range: 0.02-0.35 x 109/L), and eosinophil percentage of 18.5% (reference range: 0.005-0.050%). Her routine urine test was normal. At the same time, we performed a dermoscopy examination of the patient's lesion, and found that linear, light-yellow, and dark red block area of unequal width was a tunnel burrow, formed in the stratum corneum by larva migration (Figure 2A). We also saw translucent round structures from the apex of the linear lesion, which had several high refractive dots internally, which might be the larval body or paws (Figure 2B).
The lesion was assessed by RCM which showed edema in the epidermis and superficial dermis, and a well-circumscribed, oval-shaped tunnel in the stratum corneum or granular layer, which could extend to the superficial dermis (Figure 3A). At one end of the tunnel, there was a well-delineated ovoid larval body and claw-like structures (Figure 3B).
Based on clinical presentation, dermoscopy, and RCM, the patient was finally diagnosed with CLM. The patient was treated with cryotherapy. Attention should be paid to the scope, time, depth, and frequency of cryotherapy, to avoid obvious scars, which could be formed by excessive treatment. Liquid nitrogen was applied to the patient's both ends of the skin rash several times using a cotton swab. After 3 days, the linear rash continued to migrate, requiring extending cryotherapy to all lesions. Seven days later, the rash still spread to the proximal part of the left upper arm and left shoulder (Figure 4A and B). Thus, dermatoscopy and RCM were performed to accurately locate the position of the larvae in the skin lesions, which were then frozen. After 14 days, the patient's pruritus significantly reduced, and the rash did not spread. Three weeks later, the lesion was completely cured, and the skin rash was completely resolved. At this time, a routine blood test showed, a white blood cell count of 8.18 x 109/L (reference range: 4.0-10.0 x 109/L), eosinophil count of 0.3 x 109/L (reference range: 0.02-0.35 x 109/L), and eosinophil percentage of 3.7% (reference range: 0.5-5.0%), and routine urine test was normal. No recurrence was noted after 2 months (Figure 5A and B). | cutaneous larva migrans, linear erythema, reflectance confocal microscopy | Not supported with pagination yet | null |
PMC10102472_01 | Male | 70 | We report the case of a 70-year-old man who presented recurrent abdominal pain and distention, accompanying skin irritation and pruritus for more than 9 months. The patient denied a family history or special occupational exposures, without drinking history, and was admitted to hospital with a possible diagnosis of decompensated cirrhosis.
On admission, physical examination revealed abdominal bulge and tenderness with shifting dullness but without jaundice and caput medusa. An abdominal ultrasound revealed multicavity effusion, especially massive peritoneal effusion. Chest-computed tomography (CT) scan showed a limited amount of pleural effusion, and contrast-enhanced abdominal CT indicated early-stage cirrhosis and splenomegaly complicated by abdominal-pelvic fluid accumulation. Beyond these, a subcapsular effusion of the right liver lobe, gastric wall edema lesion, and subcutaneous edema were in the imaging (shown in Figure 1 ). Further full-body PET-CT images correspond to contrast-enhanced abdominal CT and disclosed no significant hypermetabolism (shown in Figure 1 ). Blood tests excluded multiple organ failure and potential virus infection, which was caused by hepatitis B, C virus (HBV, HCV), Epstein-Barr (EB) virus, and Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV8) virus. The investigation of liver function showed normal hepatic enzymes in alanine aminotransferase (ALT) 13.90 U/L, aspartate aminotransferase (AST) 32.40 U/L, total bilirubin (TBIL) 9.06 umol/L, direct bilirubin (DBIL) 3.43 umol/L, indirect bilirubin (IBIL) 5.63 umol/L, and slightly increased alkaline phosphatase (ALP) 101.0 IU/L and gamma-glutamyltranspeptidase (GGT) 68.9 IU/L, while there was an obvious reduction of total protein (TP) 51.72 g/L and albumin (ALB) 24.21 g/L. A representative antibody for primary biliary cirrhosis (PBC), antimitochondrial M2 (AMA-M2), was positive. Routine blood tests indicated anemia and thrombocytopenia with red blood cell count (RBC) 3.07 x 1012/L, hemoglobin (Hb) 88 g/L, and platelet count (PLT) 115.0x109/L. Furthermore, a slight elevation in high-sensitivity cardiac troponin T (hs-cTnT) 0.019 ng/ml was also noted.
In an attempt to a definitive diagnosis, ascites and marrow were examined. The biochemical test of ascites found an abnormally high in lactate dehydrogenase (LDH) 4538.0 IU/L. Histology suggested that the ascites puncture cytology contained aggressive of large-sized B lymphocytes positive for CD20, CD79alpha, LCA, c-MYC (shown in Figure 2 ), and other biomarkers, such as PAX5(+), CD3(+), CD19(+), CD34(-), HHV8(-), Ki-67(+, 60%), BCL-6(+), MUM1(-), sox11(-), EMA(-), and MPO(+) consistent with the result of the immunohistochemical staining of bone marrow biopsy, which presented CD20(+), CD79alpha(+), CD3(+), BCL-6(-), MPO(+) (shown in Figure 3 ), CD10(-), Ki-67(+, 1%<), and MUM(-).
According to available information, a cogitative diagnoses, FOALBCL, of this patient was produced. All symptoms could be completely recovered and vanished after peritoneal drainage by percutaneous puncture catheterization. Liver dysfunction returned to normal (ALT 10.40 U/L, AST 21.40 U/L, TBIL 15.16 umol/L, DBIL 5.66 umol/L, IBIL 9.50 umol/L, ALP 79 IU/L, GGT 28.13 IU/L) and hypoproteinemia was improved (TP 64.30 g/L, ALB 35.20 g/L) after receiving albumin prepared from human plasma injection (total 130 g). Despite the fact that anemia has not been corrected (RBC 2.53 x 1012/L, Hb 77 g/L, PLT 103.0 x 109/L), myocardial enzyme indicators have normalized (hs-cTnT 0.013 ng/ml) without any targeted-oriented therapy. Over 1-monthly symptomatic and supportive treatment, the patient made a discharge decision for seeking subsequent therapy by a local hospital. Before compiling the data and writing up this manuscript, informed consent and subsequent therapies have been confirmed by conducting a telephone follow-up on the patient. Follow-up information suggested that the patient was still alive and was undergoing chemotherapy smoothly without apparent adverse effects. | pet/ct, ascites, bone marrow biopsy, case, fluid overload–associated large b-cell lymphoma, lymphoma, primary biliary cirrhosis | Not supported with pagination yet | null |
PMC5385139_01 | Female | 6 | In one study, found a variety of neuropsychological differences in a group of six-year-old LBW children when compared to age-matched children of normal birth weight (i.e., the groups differed on measures of language, visuospatial, fine-motor, and attention skills). Further, these investigators found evidence of gradient effects in this cohort with greater reductions in performance being obtained at progressively lower birth weights. Taylor and collaborators also found evidence of cognitive deficits, academic dysfunction, and greater behavioral problems in a group of middle school aged children born very low birth weight (i.e., <1500 grams). These researchers indicated that, within the extremely low birth weight group, disparities grew more pronounced on measures of global cognitive abilities, basic reading skills, academic performance, and parent-reported measures of behavior and attention as children increased in age. Finally, in a follow-up study to their 1996 paper, found that previously LBW children continued exhibiting decreases in academic skills at the age of 17.
In addition, other perinatal neurologic injuries and environmental factors such as low socioeconomic status (SES) and maternal infections may exacerbate these problems. For example, demonstrated that LBW children sustaining an interventricular hemorrhage (IVH) were more likely to exhibit a psychiatric diagnosis (especially attention deficit hyperactivity disorder) at six years of age compared to LBW children who had not sustained a concurrent IVH. showed that LBW children growing up under disadvantaged circumstances had a higher rate of attention problems when compared to LBW children growing up in circumstances with more resources.
Taken together, the above studies indicate LBW children are at a significant risk for long-term cognitive and behavioral difficulties and suggest that at least some of these deficits may be influenced by environmental factors and/or exacerbated by other perinatal insults such as an IVH. However, other investigations have suggested that children born LBW demonstrate considerable plasticity and recovery of cognitive skills following birth, and some studies have suggested that children born late preterm (e.g., between 34 and 36 weeks gestation) who are otherwise healthy do not exhibit any significant decrements in cognitive skills when evaluated years later.
Few, if any, studies have examined how LBW children respond to future neurologic injuries that occur years after birth. addressed a similar question by examining the influence of environmental stress on the rate of psychiatric diagnosis in a group of children with various handicaps. Interestingly, she found no greater adverse effect of environmental stress within the handicapped group suggesting that children with neurological dysfunction did not have greater vulnerability to environmental stress. However, this study was concerned only with increases in the rate of psychiatric diagnosis and was primarily intended to examine relatively low-level, but chronic environmental stress as opposed to a secondary injury. Other investigations have examined the relationship between LBW and complex injuries occurring secondary to premature birth. These investigations indicate that LBW children who also demonstrate brain anomalies are at a significantly higher risk for developmental or motor delays, but most of these investigations are concerned with injuries occurring soon after birth. An important question is whether LBW status contributes to long-term alterations in brain development that lead to different (i.e., more attenuated) patterns of recovery following a future neurologic insult.
Research with other populations has examined the influence of cumulative risk on long-term cognitive outcomes. Research with children who have sustained traumatic brain injuries (TBIs) suggests that these children remain at risk for significantly worse outcomes following a second injury even if one or both of the traumas was relatively minor. Further, evidence suggests that repetitive, even mild, head traumas in young adulthood may result in very long-term increases in mild cognitive impairment and earlier onset of Alzheimer's type dementia. Thus, it seems plausible that even in the context of apparently intact functioning, LBW children may be at increased risk for an attenuated recovery following future neurologic insults. This small study reports a prospective case-series of children who were part of a larger investigation on the long-term cognitive impact of traumatic brain injury (TBI) but who were also born with birth weights below 2500 grams. We hypothesized that LBW children may exhibit a different pattern of recovery following a mild, moderate, or severe TBI when compared to a group of normal birth weight children who had sustained a TBI of similar severity. | academic functioning, adaptive functioning, children, development, language, low birth weight, reading skills, social adaptation, traumatic brain injury, verbal memory | Not supported with pagination yet | null |
PMC5859870_01 | Male | 34 | A 34-year-old man was admitted to the Surgery Department in our centre in July 2016 with diffuse abdominal pain, dyspnea, general fatigue, and weakness. In his medical history, he had been admitted to another centre two months ago for an episode of acute pancreatitis.
Abdominal ultrasonography revealed a heterogeneous area of 5 cm in size in the body of the pancreas, peripancreatic fluid, gallstones with thickness in the gallbladder wall, and multiple cysts in the left kidney. Abdominal computed tomography (CT) showed heterogeneous collection of fluid with a thick wall of 12 x 4 cm in size along the body of the pancreas and left colic angle (often an abscess or a pseudocyst) with infiltration of adipose tissue around it and mild thickness at the wall of the colon. A simple renal cyst was also reported in the left kidney (Figure 1).
Laboratory investigations were within normal levels except an elevation in C-reactive protein value (18.1 mg/dl) and amylase (765 U/L). The hepatic tests were within the normal range (total bilirubin (TB) was 0.64 mg/dl, alanine aminotransferase (ALT) was 20 IU/L, and aspartate transaminase (AST) was 19 IU/L). The patient was treated as an episode of acute pancreatitis.
Other investigations were performed; upper gastrointestinal endoscopy (UGI endoscopy) demonstrated an esophagitis (grade A) at the lower esophagus, incompetence of the lower esophageal sphincter (LES), diffuse congestion of the mucous membrane of the stomach, and aphthous ulcer at the fundus of the stomach. Lower GI endoscopy was normal until the terminal ileum.
A month later, the CT scan for thorax and abdomen data were similar to the previous finding, and the pancreatic cyst measuring 13.5 x 7 cm stretched down through the peritoneal cavity in front of the mesenteric vessels.
The laboratory values were normal, and a primary diagnosis of pancreatic pseudocyst was probable, and the decision of surgical intervention was decided.
Intraoperatively, an extreme oedema in the pylorus, the transverse mesocolon, the head and body of the pancreas, and the hepatoduodenal ligament was found. A cholecystitis required cholecystectomy. After entering the lesser sac, a large mass of 35 x 20 x 15 cm in size was found, located in the space between the tail of the pancreas, spleen, left colic angle, left kidney, stomach, and diaphragm. The mass was hard to dissect from the neighboring structures. In puncture, a clear pure liquid was aspirated proposing the existence of a hydatid cyst. Cyst fenestration was performed, and multiple daughter cysts were evacuated; the endocyst membrane was removed (Figure 2). A Foley catheter was placed in the residual cavity. The simple renal cyst needs no intervention according to the urologist. The final diagnosis was pancreatic hydatid cyst.
The patient had another episode of acute edematous pancreatitis after a month of surgery, and the amylase level was over 1000 U/L. The development of local retroperitoneal abscess required puncture and drainage by CT; the patient also developed a deep venous thrombosis and was treated by anticoagulants.
During 18 months of follow-up, the patient was well with no episodes of recurrence or other complications. | null | Not supported with pagination yet | null |
PMC5843145_01 | Male | 39 | A 39-year-old man presented to the emergency department complaining of a 3-day history of shortness of breath and dry cough. He had no known significant co-morbidities and did not report any further associated symptoms. He reported that he was treated with antibiotics for a lower respiratory tract infection (LRTI) by a private physician in the previous 3 days with no improvement in symptoms. He was unsure of his HIV status and was not on antiretroviral therapy (ART).
His admission vitals were a blood pressure of 123/70 (82) mmHg, heart rate of 116 beats per minute, respiratory rate of 30 breaths per minute and a temperature of 36.9 C. On examination, he had no significant lymphadenopathy and was not found to have mucosal or skin lesions associated with advanced HIV. No other obvious stigmata of advanced HIV were noted. He was in severe respiratory distress with scattered bilateral predominantly basal crackles on auscultation. Wheezing was not present on auscultation. He had an oxygen saturation of 62% on a partial rebreather mask with an inspired oxygen fraction (FiO2) of 80%.
Laboratory investigations revealed a white cell count (WCC) of 14.5 x 109 cells/L, haemoglobin (Hb) of 11.6 g/L, platelets of 298 x 109 cells/L, urea of 6.3 mmol/L, creatinine of 108 mumol/L, C-reactive protein (CRP) of 102 mg/L and beta-d-glucan (BDG) of > 500 pg/mL. His admission blood gas showed a mixed respiratory and metabolic acidosis with type II respiratory failure and a markedly increased alveolar-arterial gradient (pH = 7.36, pCO2 = 34.7, pO2 = 64.8, HCO3 = 19.2, BE = -4.9, SpO2 = 96.9, Hb = 13.4, Lac = 4.4). His chest X-ray (CXR) showed diffuse bilateral alveolar infiltrates and granular opacities. A transthoracic echocardiogram performed at the time of admission showed normal left ventricular function, no evidence of pulmonary embolus and normal heart valves. Based on clinical suspicion, hypoxaemic respiratory failure with typical chest radiograph changes, the patient's normal echocardiogram, elevated BDG, and the relative absence of clinical signs usually associated with a multilobar pneumonia, the diagnosis of Pneumocystis pneumonia (PCP) was considered.
On the basis of his clinical condition and investigations, the patient was intubated, ventilated and admitted to the intensive care unit (ICU) for respiratory support. He was empirically started on treatment for partially treated community acquired pneumonia (CAP) (piperacillin and tazobactam and a macrolide) as well as PCP, on the basis of clinical case definition as suggested by the World Health Organisation (WHO), with high-dose intravenous trimethoprim-sulfamethoxazole (TMP-SMX) and high-dose intravenous corticosteroids (hydrocortisone). He consented to HIV testing on admission and was found to be HIV-infected with a CD4 count of 7 cells/muL. Additional sputum and blood investigations for Mycobacterium tuberculosis (TB) including TB culture (sputum and blood) and Auramine O stain, real-time polymerase chain reaction (PCR) (TB GeneXpert), sputum gram stain and bacterial culture and direct fluorescence antigen test for PCP were negative. Standard aerobic and anaerobic blood cultures yielded no pathogenic organisms.
The patient was intubated and ventilated for 3 days and spent a week in our unit. During this period, we adopted a lung protective ventilation strategy, permissive hypoxaemia as well as meticulous fluid management. Through his week-long admission, he had a cumulative fluid balance of -332 mL. Initial pre-admission ventilator settings of FiO2 = 1, PEEP = 14 and DeltaP = 8 were successfully weaned to FiO2 = 0.6, PEEP = 10 and DeltaP = 10 on day one of admission. We accepted oxygen saturations in the region of 70%-80% and PaO2 measurements in the region of 50 mmHg - 60 mmHg whilst maintaining tidal volumes of 4 mL/kg - 6 mL/kg. On day four of admission, despite oxygen saturations in the region of 80%, the patient was successfully extubated and placed on non-invasive ventilation (NIV). He required NIV (positive end expiratory pressure of 6 cm H2O and pressure support of 6 cm H2O) for a total of 3 days before being weaned onto oxygen supplementation with an FiO2 of 0.4. He maintained oxygen saturations in the region of 85%-90%. He was discharged to the ward on nasal cannula after a 7-day ICU stay. | null | Not supported with pagination yet | null |
PMC8491585_01 | Female | 71 | A 71-year-old woman visited our hospital on September 2, 2020 due to shortness of breath and palpitation after exercise 1 day ago. The symptoms occurred once only and were inactive on admission. Figure 1 shows the timeline of this case. She was diagnosed with sick sinus syndrome with normal atrioventricular conduction and had a single-chamber AAI pacemaker implanted in 2004. The pacemaker was implanted on the right side because of left-handedness. The battery ran out 10 years later and she was admitted to our hospital in 2014. Similar single-chamber pacemakers were not available and not covered by the patient's medical care program anymore. Moreover, her atrioventricular node function had shown to be slightly reduced with age. Thus, the pacemaker was upgraded to a dual-chamber one back then. The atrial lead was kept, while a new ventricular lead was implanted. The patient did not routinely go to follow-up visits in the following 5 years. A chest X-ray image from December 2019 showed that both leads were intact (Figure 2a). Eight months prior to this admission (January 2020), she fell off from a running bicycle, causing blunt force trauma to her right subclavicular region. She went to a community hospital and underwent a chest X-ray screening. It showed a complete right-ventricular pacemaker lead fracture (Figure 2b). The fractured lead was seen at the level of the right clavicle, while the proximal end of the lead was still attached to the pacemaker. The atrial lead was still intact. The patient was suggested to go to a superior hospital for further evaluation and treatment. However, she refused to do so, thinking that it was unnecessary due to the lack of any specific symptoms back then. She was then discharged and did not have any medical visits or hospitalization until this time. Her comorbidities included stable angina and hypertension.
Physical and laboratory examinations on this admission showed no significant findings. Myocardial enzyme test had negative results. Her electrocardiography (ECG) showed atrial pacemaker rhythm and no specific ST-T changes. Chest X-ray scanning had similar findings as compared with 8 months ago, showing a complete ventricular lead fracture (Figure 2c). The results of chest fluoroscopy confirmed that the free end of the fractured ventricular lead was in a fixed position and did not move with heartbeats or change of body position (Figure 3). The patient then underwent a 24 h Holter monitor to further examine the status of her pacemaker. The results showed satisfying atrial sensing and pacing with an AAI pacing mode. Further examinations including coronary angiography and coronary CT angiography were refused by the patient. After symptomatic treatment and observation, the patient was discharged 7 days after admission. The patient had paid follow-up visits routinely after discharge and there were no symptoms up to her latest visit on January 12, 2021. | complication, lead fracture, pacemaker | Not supported with pagination yet | null |
PMC2666463_01 | Unknown | 24 | Other authors who have described their experiences in dealing with severe joint limitations have also carried out arthroplasty in young patients. Schurman et al. described arthroplasty of an ankylosed knee in the case of a 24-year-old patient. Given the young age of these patients and the possible need for future revision, we sought to perform arthroplasty in the least aggressive manner possible. For this, we used prostheses without posterior stabilization, and we did not replace the patella, since there was less bone resection.
Aglietti et al. described their experience in treating knees with severe joint limitations using prostheses with posterior stabilization. We believe that, although the bone resection and consequent ligament resection are extensive in cases of ankylosis, the anteroposterior stability in this group of patients is less important, due to the limitation of movement that consistently remains.
Postoperative rehabilitation was carried out by a physiotherapist. We did not use continuous movement equipment, since we judged that it was not necessary to detect any adherence or movement restriction within the first 72 hours", since we judged that it was necessary to detect any adherence or movement restriction within the first 72 hours. If any limitations were present, the intensity of the manipulation could have been immediately increased. Manipulation of postoperative joint limitations should be performed as early as possible, as suggested by Yercan et al.
Improved movement was observed in all of our patients, although a limitation of five degrees of extension occurred in four patients, and the mean flexion gain was 65 . Naranja et al. described a mean flexion gain of 62 in a multicenter study. Rajgopal et al. reported a mean flexion gain of 61 in 84 knees of 54 patients who presented severe joint limitation.
A significant reduction in pain was observed in all our patients, in addition to gains in movement. However, we were unable to reestablish normality for any of the cases.
From a two-year follow-up of a series of nine cases similar to ours, Bradley et al. considered their results to be satisfactory with regard to reductions in pain and partial gains in movement.
Rajgopal et al. presented a series of 84 knees among 53 patients with severe joint limitation. After a mean follow-up of nine years, they considered their results to be good because their patients experienced reduced pain and improved quality of life.
In the present study, two serious complications that required extensive revision occurred. Both were due to infections, and one of our patients developed ankylosis as a consequence of infection.
Kim et al. performed arthroplasty in 16 patients with ankylosis of the knee following pyogenic infection or tuberculosis. In most of those cases, the results were satisfactory, with postoperative infection occurring in just two cases.
In a multicenter study of 35 patients who underwent total arthroplasty of their ankylosed knees, Naranja et al. reported an early complication frequency of 24% and a major complication frequency of 35%. The frequency of infection was 14% in their group of patients.
There is no doubt that arthroplasty of ankylosed knees is a risky procedure, and this limitation must be clearly laid out for potential patients. Nevertheless, the possibility of gains in movement and significant reductions in pain may compensate for the risks.
The evident shortcoming of the present study is our small number of cases, which precluded the ability to obtain definitive conclusions.
In the event of complete failure in the attempt to perform arthroplasty, we would have performed arthrodesis, the only procedural indication for this group of patients other than arthroplasty.
However, based on the latest follow-up, there had been no need to perform arthrodesis for any of our patients. | null | Not supported with pagination yet | null |
PMC2416759_01 | Male | 20 | A 20-year-old homeless white male (JO) was informally admitted to a psychiatric unit after reports of fire-setting behavior (eg, laughing while setting individuals on fire with lighter fluid). As a child, he had set fire to a hillside barn, which would have had significant consequences for a village further up the hill had it not been extinguished. When admitted to the unit he was found to be grossly cognitively impaired. However, collateral information indicated that previously he was an average student, completing 10 years of education. He did not exhibit behavioral problems during the last several years of his education. The patient had brief periods of manual labor employment, the longest lasting 3 months. He denied having had any long-term relationships. He has had limited contact with his mother. The patient's father was a heavy drinker and committed suicide two years previously, several months after losing his business. Police databases did not show a formal forensic history for the patient.
On admission to the ward, JO was noted to have low mood associated with anhedonia, reduced motivation, and cognitive depressive symptoms. He also had persecutory delusional ideas; thinking that others talked about him and mocked him. He admitted to fleeting visual and auditory hallucinations. These consisted of hearing "breathing" in his bedroom and seeing blood on the wall. In addition, he stated that he had seen "ghost-like people that looked like water". During a diagnostic interview the patient indicated that he had problems with memory, including difficulty remembering names, phone numbers, appointments, directions, and recent events.
Routine cognitive examination revealed difficulty with word finding and reading retention. Manual motor tasks were adequate. He was casually dressed, but dishevelled and had a blunted affect, paucity of facial expression, and poverty of speech. Significantly, he scored in the impaired range (18 correct of 30 items) on the Mini Mental Status Examination (MMSE), doing poorly on measures of short-term memory, concentration, and orientation in time. He seemed to be making a genuine effort to complete the tests, and he appeared perplexed at his inability to answer questions. From the diagnostic interview it was apparent that fire setting did not occur as an accident during a confusional state such as alcoholism or drug intoxication. Moreover, fire setting did not occur during an acute manic episode or psychotic episode in specific response to a delusional idea or commands from hallucinated voices. The patient did not meet the criteria for conduct disorder, as most of his behavioral problems were limited to verbal outbursts. As a child he did not make the association between fire setting and the potential harm it might present to others.
His characteristic ward behavior was described as being withdrawn with poverty of speech. However, during an interview, a rapid change in affect occurred when questioned about what he did for entertainment. The patient began to laugh and smile indicating that he "enjoyed putting lighter fluid on people and setting them on fire". The patient continued to be animated while discussing violent topics (eg, what it would be like to drop objects from motorway bridges to cause an accident). He was also at times sexually inappropriate toward female staff and talked of his wish to travel to a foreign country for "loads of sex". On another occasion, he asked a female mental health worker if she could arrange for prostitutes dressed as nurses to visit the inpatient ward.
Previously, JO had experienced two episodes of collapse for which he was admitted to hospital. On both occasions he had normal CT scans and a normal EEG. These collapses were attributed to illicit drug use, probably opiates. He had experimented with other drugs including marijuana but did not evidence signs of dependence. During the current admission, however, nursing staff observed 2 generalized tonic-clonic seizures. Routine bloods were normal as were lumbar puncture (including testing for new variant Creutzfeldt-Jakob disease [nvCJD]), HIV screening, and EEG. Testing for nvCJD was undertaken due to the severity of JO's cognitive impairments. An MRI examination demonstrated evidence of generalized cerebral atrophy. JO was initially treated with an anticonvulsant sodium valproate (300 mg bd, increased to 800 mg bd; serum levels confirmed dose in therapeutic range). No further seizures were observed. Olanzapine was commenced 5 days after sodium valproate. Neuropsychological tests were administered on admission and were repeated 5-months later. Olanzapine 10 mg was started after baseline testing and maintained throughout the 5-month psychiatric hospitalization. Perceptual abnormalities and paranoia resolved following the introduction of olanzapine. While behavioral disturbance gradually abated, cognitive function gradually improved (see below).
The neuropsychological test battery was designed to assess multiple domains of cognition including premorbid intelligence (National Adult Reading Test), sustained attention and concentration (Continuous Performance Test), cognitive flexibility and executive function (Verbal Fluency), language (Boston Naming Test), verbal memory (Rey Auditory Verbal Learning Test), visual memory (Rey Complex Figure Test), and visuospatial function (Parietal Lobe Test). Frequency of serious clinical incidents (eg, self-harm, threatening behavior, and verbal abuse) were noted by the treating psychiatrists, nurses, and mental health workers and documented in the medical charts. | executive function, homelessness, neuropsychological assessment, olanzapine, psychopharmacological treatment, pyromania, sodium valproate | Not supported with pagination yet | null |
PMC8825631_01 | Female | 36 | A 36-year-old woman presented with a 4-month history of progressive, ulcerating plaques on both legs. One month prior to the onset of her rash, she noted bilateral swelling and decreased range of motion of her hands and feet.
The physical examination confirmed these findings and also revealed bilateral pitting edema of lower limbs. Her cutaneous examination revealed multiple indurated plaques with central ulceration on both legs (Figure 1(a)). There was no palpable purpura nor livedo reticularis. Coincidentally, she was also noted to have multiple yellowish papules diffusely scattered on the posterior neck (Figure 2(a)). These lesions were present since childhood. Her family history was unremarkable, and she denied any cardiac or ophthalmologic symptoms.
The patient did note polyarthralgia of her hands and ankles, and tenderness of the right Achilles tendon. She also noted paresthesia of her feet. A musculoskeletal (MSK) ultrasound of her hands, wrists, ankles, and feet showed no synovitis. X-ray imaging of the affected joints showed no erosions.
Her past medical history is significant for intellectual disability and a seizure disorder, both sequelae of an episode of meningitis as a child. Her medications at the time of presentation included levetiracetam, dilaudid, levonorgestrel-releasing intrauterine system, and acetaminophen. Her medications were long-standing, and there were no recent changes.
Her laboratory investigations included a normal complete blood count, normal mean corpuscular volume, normal renal function, normal liver profile, normal coagulation profile, and normal urine analysis. Her antinuclear antibodies, extractable nuclear antigen antibodies, lupus anticoagulant antibodies, and antineutrophil cytoplasmic antibodies (ANCA) serologies were negative. Hepatitis B, Hepatitis C, and HIV serologies were negative, and QuantiFERON-TB Gold was negative. Computerized tomography (CT) of the chest, and CT angiogram of the abdomen, and pelvis were unremarkable.
A biopsy at the border of the ulcer revealed a necrotizing medium vessel arteritis present in the dermis most suspicious of PAN (Figure 1(b)). Furthermore, she was seen by rheumatology who found she had no signs of systemic vasculitis particularly given the normal CT angiogram and MSK ultrasound showing no synovitis. Her presentation was consistent with limited or cutaneous PAN, and thus she was started on oral prednisone with the addition of celecoxib. She initially responded well to prednisone with almost complete resolution of her pretibial lesions. However, upon tapering the prednisone, her lesions recurred and she has since been maintained on hydroxychloroquine and methotrexate with excellent control.
In addition, her neck lesions were suspicious PXE, and thus one of the papules was biopsied. The biopsy showed clumped elastic fibers in the mid and deep reticular dermis suggestive of PXE. Von Kossa stain highlighted the clumped elastic fibers (Figure 2(b)).
Given the suspicion of PXE, she underwent cardiac, gastroenterological, and ophthalmologic evaluations which were within normal limit. Genetic testing for mutations associated with PXE was normal including an absence of ABCC6, ENPP1, and GGCX mutations. Furthermore, genetic testing for CECR1 mutations, which has been reported with PAN, was also normal. The patient also has a normal array comparative genomic hybridization (CGH). Thus, the cutaneous findings were most in keeping with PXE-like phenotype. | cutaneous polyarteritis nodosa, hydroxychloroquine, methotrexate, pseudoxanthoma elasticum–like phenotype | Not supported with pagination yet | null |
PMC4352502_01 | Male | 3 | This is a case of a 3-year-old male patient, with no medical or dental history of interest, suffered a dental trauma after a domestic accident and went as an emergency to the Pediatric Dentistry Service of the Hospital.
Chief complaint: his mother went to the emergency room with the fragment of her child's tooth root in her hand, explaining that she had found this "loose canine in the child's mouth" after a dental trauma. In the physical examination, the following was found: a bruise, abrasion, and laceration of the maxillary buccal mucosa and gingiva of the primary maxillary central incisors zone. There was mobility in the primary maxillary right central incisor and light mobility without displacement in the primary maxillary left central incisor. The clinical and radiological exploration of the lateral incisors was normal, without any pathology. The patient presented with anterior open bite because of pacifier habit persistence.
Periapical radiographic examination revealed the near complete absence of the primary maxillary right central incisor root. This exploration provided evidence that the patient had suffered a root fracture of the primary maxillary right central incisor (fracture located to cervical part of the root) accompanied by transalveolar and transmuco-gingival avulsion of the tooth root fragment (Figure 1). The dental crypts of the maxillary alveolar process of the developing permanent teeth were found without any radiological alteration (the dental follicle of the permanent maxillary right central incisor was in 5 Nolla stage).
Root avulsion of the primary maxillary right central incisor, subluxation of the primary maxillary left central incisor, and fracture of the alveolar process were diagnosed.
An antibiotic regimen of amoxicillin-clavulanic acid was started as a treatment for one week. Soft diet was recommended and oral hygiene instructions were explained (brush with a soft brush after every meal). It was also recommended to apply chlorhexidine 0.1% topically to the affected area with cotton swabs twice a day for one week and to restrict the use of a pacifier, as well as to avoid putting pressure on the traumatized area.
Several posttrauma follow-up appointments were performed, exactly 15 days, one month, and three months after the trauma.
During the first examination, 15 days after the trauma, the clinical intraoral examination showed that the buccal mucosa of the primary maxillary right central incisor was healing, and the periapical radiography showed absence of the primary maxillary right central incisor root, but without any alteration or pathological image. The crown of the primary right central incisor did not present mobility (it was in its initial position in the dental arch) and there was not any risk of aspiration. In addition to this, the child had already given up the pacifier habit, as it was recommended in the posttrauma instructions.
Another examination was performed one month after the trauma. The clinical intraoral examination showed normal buccal mucosa and the primary maxillary right central incisor crown did not show mobility. A periapical radiography was also performed.
Another examination was performed 3 months after the trauma (Figure 2). The clinical intraoral examination showed a perfectly healed vestibular mucosa with normal appearance and mobility of the primary maxillary right central incisor crown. A periapical radiography was also performed.
After the last examination, the patient went to the emergency room three more times because he suffered different traumas on the primary maxillary right central incisor (playing football, hitting himself with a chair, and running). A lacerated contused wound in the lower lip was observed during the last physical trauma examination, as well as an abrasion injury on the chin (Figure 3).
Four months after the trauma, the primary maxillary right central crown remained in its position in the dental arch.
As there was a lack of occlusal contact with the opposing tooth, which would have caused the crown extrusion, the tooth remained in his mouth. This absence of occlusal contact was due to the anterior open bite caused by the former pacifier habit.
Six months after the trauma, the patient's mother called to tell us that the primary maxillary right central incisor crown had been exfoliated and we appointed another examination to assess the state of the crown and alveolar bone (Figure 4).
After the exfoliation of the primary maxillary right central incisor crown, the growth and development of the patient had to be monitored in order to check the eruption of the permanent maxillary incisors. After an 8-year follow-up, the permanent maxillary central incisor had normally erupted (Figure 5). | null | Not supported with pagination yet | null |
PMC9897714_01 | Male | 18 | An 18-year-old male with a history of epilepsy on levetiracetam, chronic constipation and abdominal pain since infancy, and chronic nocturnal enuresis since infancy started on imipramine one week prior and presented with a painful, itchy, diffuse skin eruption that worsened over 24 hours. The patient initially had tense vesicles on his neck, ears, and upper chest the previous day when evaluated by outpatient Allergy and Immunology. He was advised to discontinue imipramine due to concern for drug allergies and was prescribed empiric valacyclovir for herpes simplex virus and trimethoprim-sulfamethoxazole for bullous impetigo. However, the eruption then quickly spread to include his lower lip, abdomen, arms, and legs. The patient noted that the vesicles were tense and painful, especially after bursting. Additionally, the patient noted fatigue, generalized weakness, chronic constipation, abdominal pain in the bilateral lower quadrants with bowel movements, and occasional bright, blood-coated stools. The patient denied fever, chills, intraoral or esophageal lesions, odynophagia, dysphagia, arthralgia, myalgia, melena, nausea, vomiting, headache, and new exposures prior to the rash eruption, including poison ivy, new hygiene products, or new detergents.
Initial physical examination revealed the patient was afebrile, hemodynamically stable, with vesicles noted in the external auditory canals, moist mucous membranes without mucosal lesions, and a diffuse eruption with vesicles and bullae noted on the outer aspect of the lower lip, posterior neck, upper back, chest, arms sparing the palms, and legs sparing the soles. Some of the lesions appeared to be tense bullae, while others were less tense and umbilicated primarily on the dorsal hands and feet. Some of the lesions had burst, but most notably, there was a negative Nikolsky sign. Over the next few days, bullous lesions clustered in the classical pattern of a "string of pearls," as demonstrated in Figures 1-6.
Initial work-up included negative swabs via PCR for herpes simplex virus 1, herpes simplex virus 2, and varicella zoster, as well as a superficial wound culture of the posterior neck with rare Staphylococcus aureus. Laboratory findings included leukocytosis with eosinophilia, neutrophilia, mild monocytosis, microcytic anemia with iron deficiency, reticulocytosis, thrombocytosis, elevated inflammatory markers, elevated haptoglobin, and low ferritin (Table 1). The complete metabolic panel and lactate dehydrogenase levels were within normal limits (Table 1). The autoimmune workup was negative for the anti-nuclear antibody screening test, anti-double-stranded DNA antibodies, anti-Smith antibodies, anti-nuclear ribonucleoprotein antibodies, anti-Jo-1 antibodies (histidyl-tRNA synthetase), anti-Sjogren's-syndrome-related antigen A autoantibodies (anti-SSA/ro antibodies), anti-Sjogren's-syndrome-related antigen B (anti-SSB) autoantibodies, and scleroderma (Scl-70) antibodies. Complement component 3 (C3) and complement component 4 (C4) were within normal limits (Table 1). Immunoglobulin serum levels revealed elevated IgG1 subclasses (Table 1). Further work-up revealed negative results for the direct Coombs test, cold agglutinins, serum porphyrins, urine porphyrins, urine porphobilinogen, and 6-methylmercaptopurine. The glucose-6-phosphate dehydrogenase level was within normal limits (Table 1). A peripheral smear conducted during the hospitalization revealed mild neutrophilia attributed to the treatment plan, microcytic anemia secondary to iron deficiency and blood loss, reticulocytosis for bone marrow compensation, and reactive thrombocytosis attributed to anemia. Flow cytometry of peripheral blood had no abnormal findings. The infectious work-up was negative for HIV, hepatitis B, hepatitis C, and tuberculosis via QuantiFERON. A gastroenterological work-up revealed a positive fecal occult blood test (FOBT), significantly elevated fecal calprotectin, and negative transglutaminase IgA antibodies (Table 1). The patient had mild zinc insufficiency and an elevated vitamin B12 level, but levels for vitamin E, chromium, niacin, vitamin B6, folate, and copper were within normal limits (Table 1). Two skin-punch biopsies of the right posterior shoulder revealed a subepidermal cleft or blister with neutrophils at the tips of the dermal papillae. Direct immunofluorescence testing of the skin biopsies revealed continuous, strong linear basement membrane deposition of IgA, consistent with linear IgA bullous dermatosis.
The patient underwent esophagogastroduodenoscopy (EGD) and colonoscopy; EGD revealed a non-bleeding duodenal erosion, and duodenal biopsies were taken (Figure 7). Duodenal biopsies revealed duodenal bulb mucosa with gastric foveolar metaplasia consistent with mild peptic injury and notably negative for signs of celiac disease, malignancy, viral inclusions, and granuloma. Colonoscopy revealed moderately active (Mayo Score 2), left-sided ulcerative colitis with random colonic biopsies taken (Figures 8, 9). Random biopsies of the left colon demonstrated chronic, moderately active colitis, while random right colon biopsies revealed focal, chronic, but inactive colitis.
Imipramine was discontinued before hospitalization and not resumed due to the suggestion of drug-induced dermatosis. The patient was started on oral prednisone 10 mg when eruption failed to improve with supportive care after receiving one dose. The corticosteroid regimen was up-titrated the following day for worsening pain to methylprednisolone 125 mg intravenously twice daily, for which the patient received four days of treatment. As the eruption had improved, the patient was weaned to oral prednisone 40 mg daily, receiving two days of therapy before the eruption worsened again. Oral prednisone was increased to 60 mg with the addition of oral azathioprine 50 mg twice daily. Despite this, the eruption worsened, which necessitated further up-titration of corticosteroids to methylprednisolone 500 mg intravenously daily for three days while continuing azathioprine at the current dose. Treatment with oral dapsone was initiated, partly as a steroid-sparing medication for LABD and partly for Pneumocystis jirovecii prophylaxis. After completion of the intravenous methylprednisolone three-day course, the patient was transitioned to oral methylprednisolone 64 mg daily, at which point azathioprine was also stopped. Treatment with infliximab was initiated after discharge due to findings of ulcerative colitis on a colonoscopy. The patient was ultimately discharged on oral methylprednisolone, dapsone, and infliximab infusion as an outpatient. On follow-up four weeks and three months later, the patient had complete resolution of skin lesions, with moderate pigmentation at the site of some previous skin lesions but no scars and no abdominal pain. | autoimmune bullous dermatosis, corticosteroid treatment, dapsone treatment, drug -induced, linear iga bullous dermatosis, string-of-pearls sign, ulcerative colitis (uc), vesiculobullous skin lesions | Not supported with pagination yet | null |
PMC6280337_01 | Female | 76 | A 76-year-old Caucasian female attended our pulmonology outpatient clinic with a four-week history of cough with mucous-purulent sputum and dyspnea. The patient was a nonsmoker and had worked for a few years in a cotton factory. Her past medical history was negative for any contact with substances known to be associated with lipoid pneumonia. She had not travelled recently and had no pets. She had been treated for atrial fibrillation with amiodarone (200 mg OD) for 30 years, systemic hypertension, diabetes mellitus type II and hypothyroidism. Physical examination revealed a well built and nourished patient with pulse rate 69 per minute and blood pressure 110/70 mmHg. Vital signs were within normal range with SpO2 of 95% in room air. Her physical examination revealed bibasal lung crackles, but no evidence of pallor, icterus, cyanosis, clubbing or lymphadenopathy. Her blood work-up was within normal range. Pulmonary function testing demonstrated moderate restrictive lung disease and decreased diffusion capacity. (see Table 1).
Since chest X-ray showed bilateral infiltrates, a high resolution computed tomography (HRCT) was conducted. The latter revealed areas of ground glass appearance significantly in the lower lobes of both lungs and airspace consolidations were seen as well (Fig.1, [a], [b]). The shadows improved 2 years later (Fig. 1, [c]).
Radiologically, differential diagnosis included atypical pneumonia, interstitial lung disease and tuberculosis was ruled out. The patient underwent fiberoptic bronchoscopy for bronchial wash and bronchoalveolar lavage (BALF) was collected for immunological studies as well. The bronchial washings were sent for smear for acid fast bacilli and cytological examination. No microorganisms were isolated by 48bacteriological examination and no malignant cells were found.
The total cell count of the BALF was 287,500/ml. The cells consisted of macrophages (64%), lymphocytes (31%), neutrophils (3%), and eosinophils (2%). The evaluation of BALF with specific staining and coloration showed the presence of fat-laden macrophages (oil red O stain). Figure 2 [a], [b] Extracellular oily droplets were found on a sputum cytology examination. These findings were suggestive of lipoid pneumonia.
a
The patient had never aspirated or inhaled mineral or vegetable oils and she had never used petroleum jelly intranasally or extra-nasally as decongestant. However, it is described in the literature that chronic use of amiodarone can cause endogenous lipoid pneumonia (phospholipidosis). Amiodarone, as an amphiphilic cationic compound, interferes with the movement of phospholipids across intracellular membranes and inhibits phospholipid catabolism through its potent inhibitory effect on lysosomal phospholipase 2. Drug-induced phospholipidosis assumes the form of a 'foamy cell 'response.
In our case, the patient had been taking amiodarone (200 mg OD) for 30 years which was considered the most likely cause. It was therefore discontinued and replaced with digoxin (0.25 mg OD) for the treatment of atrial fibrillation. She was also started on oral prednisolone (20 mg OD) which was gradually tapered over a period of six months. | amiodarone, bronchoalveolar lavage, endogenous lipoid pneumonia, prednisolone treatment | Computed tomography images of a 76-year-old female with lipoid pneumonia revealed ground-glass opacities and bronchiectasis in both lungs. |
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PMC9527530_02 | Male | 58 | The Proband's brother is a 58-year-old man who presented with appendicular and low back pain with progressive reduced manual dexterity and imbalance since childhood. Due to work-related difficulties and a clinical suspicion of CMT neuropathy, he was referred to the neuromuscular clinic for specialist evaluation. He had elective carpal tunnel decompression surgeries at a private clinical facility (data not available for review) and underwent magnetic resonance imaging of the lumbar spine with and without contrast at an external facility that showed broad-based disk bulge, bilateral facet joint degeneration changes, and mild-to-moderate bilateral neuroforaminal narrowing at the L4-L5 and L5-S1 levels, associated with Grade 1 L5-S1 anterior spondylolisthesis. Prior to his initial neuromuscular clinic evaluation, he underwent lumbar epidural spinal injections at a private practice pain clinic that improved the pain and numbness in his feet. He mentioned that his older sister had been diagnosed with CMT neuropathy as a teenager.
Examination revealed muscle atrophy of the hands, feet, and distal legs with high arched feet and high steppage gait. Confrontational strength testing based on the MRC scale showed finger abduction, adduction and extension (4/5), ankle plantarflexion (3/5), and ankle dorsiflexion (2/5) weakness bilaterally. All other muscle groups were normal. Sensory examination revealed subjectively decreased proprioception and absent vibratory sense at the hallux with decreased light touch and pinprick sensation below the knees bilaterally. Myotactic stretch reflexes were absent at the ankles and normal elsewhere.
Comprehensive laboratory tests for acquired causes of polyneuropathy (comprehensive metabolic panel; complete blood count with differentials; hemoglobin A1c; thyroid function tests; vitamins B1, B6, B12, and D levels; serum electrophoresis; serum immunofixation; Lyme disease serology; autoimmune neuropathy panel [antiganglioside IgG/IgM, anti-myelin-associated glycoprotein IgM; and anti-sulfate-3-glucuronyl paragloboside IgM antibodies]), and 24-hour urine heavy metal screen was normal. EDX studies (Table 1) demonstrated a moderately severe, chronic length-dependent predominantly axonal sensorimotor polyneuropathy with some demyelinating features and no conduction block, as seen in DI-CMTB.
To evaluate a clinical suspicion of autosomal dominant CMT neuropathy in our patients, the Hereditary Neuropathy genetic test panel was performed by GeneDx (Gaithersburg, Maryland) using oral rinse specimens. Using genomic DNA from the submitted specimens, the coding regions and splice junctions of the genes in the panel were enriched via GeneDx's proprietary-targeted capture system. These targeted regions were sequenced simultaneously using massively parallel (NextGen) sequencing on an Illumina platform using pair-end reads. Bi-directional sequence was assembled, aligned to reference gene sequences based on human genome build GRCh37/UCSC hg19, and analyzed for sequence variants.
Genetic testing identified a heterozygous missense point mutation in exon 15 of the DNM2 gene (c.1609 G>A) on chromosome 19, resulting in substitution of glycine 537 to serine (p.Gly537Ser) in the Proband and her brother (see arrow, Figure 2). This is a non-conservative amino acid substitution, which likely impacts the highly conserved PH domain protein structure and function based on GeneDx's in silico analysis. Importantly, a different amino acid substitution at the same position, c.1609 G>T (p.Gly573Cys), and the same point mutation in a nearby residue, c.1597 G>T (p.Gly533Cys), are associated with DNM2-related disorders. As the mutation had neither been previously published as a pathologic variant nor reported as a benign variant, it was initially classified as a variant of undetermined significance.
Due to our high index of suspicion that this mutation was pathogenically significant based on the clinical phenotypes that were consistent with CMT neuropathy and the potential impact of the mutation on secondary protein structure or function, the patients' undiagnosed symptomatic mother and asymptomatic father underwent targeted genetic testing. Their mother possessed the same heterozygous missense DNM2 point mutation which was absent in their father (Figure 2), supporting our inference that DNM2 (c.1609 G>A) is causative of DI-CMTB in this family cohort.
During follow-up neuromuscular clinic visits over the next 2-3 years, the Proband (case 1) reported increased falls despite wearing AFOs; worsening pain in multiple joints, including her hips and knees; progressive weakness in her hands with reduced dexterity; and persistent paresthesias in her feet, adequately treated with Gabapentin. Her brother (case 2) reported worsening hand and leg strength and progressive difficulty standing for prolonged periods and walking. He decided against using AFOs due to perceived discomfort and walked cautiously to prevent falls without using ambulatory aids. | charcot-marie-tooth neuropathy, dynamin 2, case report, familial genetic studies, pathogenic gene mutations | Not supported with pagination yet | null |
PMC4501502_01 | Male | 24 | A 24-year-old man consulted his primary care physician with general fatigue and chest and back pain. Chest radiography demonstrated a left-sided pleural effusion that was diagnosed as a parapneumonic effusion, and he was treated with oral levofloxacin 500 mg per day. However, neither the pain nor effusion improved; therefore, his primary care physician referred him to our institution.
He had low-grade fever without any symptoms of either respiratory disease or heart failure, but he had a history of interventional RFA for paroxysmal atrial fibrillation three month prior to the onset of symptoms. On physical examination on admission, his temperature was 37.4 C, heart rate 93 beats per min, blood pressure 110/50 mmHg, respiratory rate 16 breaths per min, and pulse oximetry 97% oxygen saturation in room air. Radiography and computed tomography (CT) of the chest demonstrated a left-sided intermediate pleural effusion and slightly thickened parietal pleura. A transthoracic echocardiogram revealed 75% of left ventricular ejection fraction without regional wall motion abnormalities and normal level of pericardial effusion. The result of laboratory examinations were unremarkable except for a trivial increase of C-reactive protein (CRP) level of 0.46 mg/dL. QuantiFERON-TB Gold In-Tube assay was negative. Thoracentesis revealed a nonbloody exudative effusion with lymphocytosis. There was no evidence of infection or neoplasia in either the culture or the cytology results.
He was diagnosed with pleuritis and was prescribed oral loxoprofen in addition to original therapy. Both his symptoms and pleural effusion gradually improved over the following month. However, seven months after his initial treatment, he complained of intense chest pain. Chest radiography and CT showed the reccurence of the left-sided pleural effusion accompanied by a thickening of the parietal pleura (Fig. 1). He had a slightly elevated CRP level at 1.72 mg/dL and a normal peripheral white blood cell count of 7350 cells/muL.
Given his previous RFA for paroxysmal atrial fibrillation three months prior to the onset of his symptoms, we believed that the series of events were highly indicative of PCIS. However, further examination was required to exclude pleural tuberculosis and malignancy. Pleural biopsy by video-assisted thoracoscopic surgery (VATS) under general anesthesia was performed, and the histological specimens from the left parietal pleura demonstrated chronic pleuritis with a non-necrotizing granulomatous reaction (Fig. 2). Furthermore, cultures and polymerase chain reaction analysis of the parietal pleura were negative for mycobacterium. He was clinically diagnosed with PCIS and was successfully treated with colchicine 1 mg and Celecoxib 200 mg daily. The dose of colchicine was reduced to 0.5 mg per day after three weeks and discontinued after one month because of the development of diarrhea. | catheter intervention, postcardiac injury syndrome, postcardiotomy syndrome, radiofrequency ablation | Chest computed tomography showed a relapse of the left-sided pleural effusion associated with a thickening of the parietal pleura seven months after the first event. |
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PMC7242870_01 | Female | 12 | A 12-year-old female patient came with her parent to the morning consultation clinic of our institute suffering from a diffuse swelling of the cheek and lower jaw on the left side with dull pain and discomfort aggravated by swallowing. The symptoms developed and gradually worsened over 8 months and was associated with weight loss and generalized weakness that had been subjectively attributed to the decreased nutrition and appetite. Initially, the patient suffered from a painful intraoral swelling involved the left side of the lower jaw. Management was sought at a local dental clinic, where extraction of a carious deciduous tooth in the area was performed. Later as the symptoms progressed, she was referred to the maxillofacial surgery unit of a local hospital. Two biopsies were taken separately from the region, only yielding inconclusive findings of inflammatory cells and fibrosis.
The patient was referred to our institute for further investigations and management. On examination, there was a slightly tender firm left-sided swelling involving the cheek, not crossing the lower border of the mandible with intact overlying skin (Fig. 1). The patient had normal mouth opening and showed no neurological deficit. Palpable mobile lymph nodes were evident at ipsilateral submandibular and deep cervical levels with no tenderness. Intra-orally, the swelling involved the ipsilateral buccal region and extended medially to the posterior lower alveolus, retromolar trigone and the ascending ramus of the mandible, with erythematous overlying mucosa (Fig. 2). Computed tomography (CT) scan, revealed an expansile lesion involving the left masticatory region, extending from the condylar process to the angle of the mandible, with bicortical erosion, and osteoblastic activity (Fig. 3). The CT findings were reported as a potentially malignant tumor. Routine laboratory blood tests were unremarkable. Incisional biopsy under local anesthesia was obtained from the lesion lateral to the ramus of the mandible. The histopathological study showed a dense chronically inflamed fibrous tissue with evidence of ill-defined granulomas with scattered multinucleated Langhans giant cells. The Ziehl-Neelsen (ZN) stain for acid-fast bacilli (AFB) detection yielded negative results in both the lesion specimen and the pharyngeal expectorate. The chest x-ray of the patient revealed bilateral enlarged hilar lymph nodes. Further investigations by Mantoux test produced 25 mm of induration at 48 h, and a PCR for MTB of blood was positive. Quadruple anti-tubercular therapy was then started at a specialized center of respiratory diseases. At the latest follow-up, one year after the diagnosis, the swelling nearly disappeared with complete resolution for the accompanying symptoms. | cervicofacial infection, iraq, mandibular osteomyelitis, oro-facial tuberculosis, osteomyelitis, tuberculosis | Not supported with pagination yet | null |
PMC3333834_01 | Male | 43 | A 43-year-old Caucasian man with AIDS presented with progressive confusion, blurring of vision, and personality change for 6 weeks in March 1999. He was successfully treated for Pneumocystis jiroveci pneumonia 2 months prior to his presentation. He did not have any headaches or seizures. He was afebrile. Examination revealed left cerebellar signs, dysphasia, and clear evidence of left posterior-occipital lesion with right homonymous hemianopia. He was unable to identify simple objects such as a pen or coins nor name colors correctly. He was disoriented in time and place. His CD4 count was 34 cells/mm3. His HIV ribonucleic acid (RNA) level was 800,789 copies/mL. Serum toxoplasma immunoglobulin G antibodies were negative. A magnetic resonance imaging (MRI) scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema (Figure 1). Cerebrospinal fluid (CSF) was clear in color with a polymorph count of three cells and a lymphocyte count of five cells. Gram staining of CSF did not show any organism, and bacterial culture of CSF was negative. CSF toxoplasma PCR was negative. CSF Mycobacterium tuberculosis culture was negative. JC virus antibodies in the blood and CSF were 1/81,920 and 1/20,489, respectively. The antibody index was 28, indicating intrathecal production of JC virus antibodies, which was consistent with progressive multifocal leukoencephalopathy (PML). Nested PCR for JC virus was positive in the CSF. | hiv, cerebral toxoplasmosis, focal neurologic signs, ischaemic stroke, primary brain lymphoma | Not supported with pagination yet | null |
PMC7074991_01 | Female | 45 | The 45-year-old female patient had received a diagnosis of seronegative RA 4 years before presentation. She had received several DMARDs including methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ). Her current treatment included leflunomide (LEF) and intermittent usage of low-dose prednisolone. Her past medical history was significant for arterial hypertension, which was treated with metoprolol and amlodipine.
The patient presented with acute symptoms, as she had been suffering from increasing pain and swelling of her right hand. Two weeks before presentation, she had already taken 20 mg prednisolone for 10 days with only slight improvement of symptoms. On presentation, there was swelling and tenderness of the third metacarpophalangeal (MCP) joint of the right hand. A flare of her RA was assumed and prednisone increased to 40 mg daily. Another 2 weeks later, she returned for a follow-up visit with new cutaneous findings: Clinical examination at that time revealed a visible and palpable swelling of the back of the right hand and third MCP joint (Fig. 1a). Other joints were not affected. A musculoskeletal ultrasound was performed and showed tenosynovitis of the third extensor tendon with increased power doppler signal (Fig. 2a and b). Laboratory analysis showed a thrombocytosis of 422 x 10^3/mul (normal range, NR: 150-350 x 10^3/mul), a leukocytosis of 15,9 x 10^3/mul (NR: 4-11 x 10^3/mul) and slightly increased CRP of 7,6 mg/l (NR: <= 5 mg/l). The differential blood count showed increased neutrophilic granulocytes with 83,9% (NR: 40-76%). Otherwise, there were no pathological findings.
Due to the novel skin findings, the patient was urgently referred to our institution's Dermatology Clinic. In addition to the findings on the right hand, a complete examination of the skin revealed a single reddish-purplish erythematous nodule in a linear "sporotrichoid" form on the right proximal forearm (Fig. 1b). No palpable lymph nodes were found in the axillary region. Upon further questioning, the patient reported regular cleaning of fish tanks and recent travel to the seaside. A clinical diagnosis of a so-called "swimmer's granuloma" was made and a biopsy scheduled for microbiological analysis. In light of this information, the nailfolds of the third and fourth right finger seemed to be the most likely site of inoculation. The histopathological analysis revealed granulomatous inflammation with necrosis. Ziehl-Neelsen staining and blood-based testing for Mycobacterium tuberculosis (using Quantiferon TB Gold Plus test) were negative. After several weeks, infection with MM was confirmed in the tissue culture.
Based on the clinical findings, immediate antibiotic treatment with clarithromycin and rifampicin was initiated. There was gradual improvement of the clinical findings over the following months. | atypical mycobacteria, immunosuppressive agents, mycobacterium marinum, rheumatoid arthritis | Not supported with pagination yet | null |
PMC8427806_01 | Unknown | 6 | To determine how tree canopy changes over the season, we conducted a temporal comparison of VO estimated fPAR for different varieties. Figure 3 shows the overall trend of VO estimated fPAR with individual almond variety and age over the growing season in 2019. In general, these different changing patterns might directly relate to the status of individual orchard management and practices. For example, canopy changes were similar for the trees in Orchards 2 and 3 that VO estimated fPAR first dropped a little from May to June or July and then bounced back in August, showing a "flat-U" shape for most of the trees excluding 6-year-old 'Nonpareil' trees continuously decreased during the season. All 11-year-old 'Nonpareil', 'Butte', and 'Carmel' varieties are from Orchard 3, where the trees might be under-irrigated during the midseason (June and July), causing a certain level of defoliation. Lampinen et al. reported continuous increases in lightbar estimated midday fPAR over time for both young (3-year-old) and mature (10-year-old) walnut orchards between April and November 2010. However, Rubke found that midday canopy fPAR increased only during the 2012 growing season, with data collected over 3 years (2012-2014). Overall, our results agreed with their findings because the majority (~50%) of our sampled trees are from Orchard 1 ('P16.013', 'P13.019', and 'Lonestar') with continuous increments of canopy fPAR over the season. The different changing patterns of the different varieties could also be attributed to their seasonal calendars. For example, as shown in Figure 2, the full bloom date and commercial harvest date for 'Nonpareil' (in Orchard 2) were on February 23 and August 20 in 2019, respectively. Most other varieties had the full bloom 1-6 days later and were harvested 2-4.5 weeks later than 'Nonpareil'.
We compared the correlations between VO and lightbar estimated fPAR over the entire growing season in 2019 at the per-row level. Table 3 shows the overall comparison of R2, RMSE (to the 1:1 line), and the regression line slopes when we force a zero intercept. R2 and RMSE are improved from May to June/July, while they remained the same level from the June/July to August (harvest). For example, they were 0.81 and 4.06%, respectively, when we tested all varieties on May 28. In June, R2 and RMSE improved to 0.91 and 2.94%, respectively, when the date of VO data collection was within a couple of days of lightbar data collection. When we tested 'Nonpareil' only, we observed similar patterns but with greater R2 (0.95-0.96) and smaller RMSE (2.06-2.27%). It can be inferred that both VO and lightbar methods measured canopy light interception similarly. So, we considered a hypothetical 1:1 correlation between the VO and lightbar measurements. All slopes of the regression lines were significantly different from the 1:1 line (95% confidence level) except for July 26, 'Nonpareil'. We then used different regression slopes for developing adjusted models for potential yield prediction using Equation 6 and summarized the results in Table 4. Comparing the regression line slopes to the 1:1 line in different days also indicated that the VO and lightbar measurements were better correlated when both data were collected within a few days. Therefore, we further calibrated and visualized the VO and lightbar estimated fPAR data in June. | aerial photogrammetry, canopy light interception, canopy profile feature, digital elevation model, digital surface model, virtual orchard | Not supported with pagination yet | null |
PMC8427806_02 | Unknown | 6 | Figure 4A visualizes the calibration of the VO estimated fPAR against the lightbar estimated midday fPAR over all varieties on June 26. Again, reasonably high R2 (0.91) and low RMSE (2.94%) from data points to the 1:1 line suggested that both methods estimate the actual canopy fPAR. However, one method estimated fPAR with lower accuracy or more error since some data points were slightly off the 1:1 line (in the dashed red). For instance, we observed that the regression line (in the dashed blue) was not completely overlapped with the 1:1 line with the slope of 0.91 in the clockwise direction of rotation (the difference was significant as shown in Table 3), indicating that most of the data points were below the 1:1 line. The result suggested that the lightbar tended to underestimate the canopy fPAR or the VO method tended to overestimate it (mean of absolute errors to the regression line: 1.97 +- 1.85%; to the 1:1 line: 5.09 +- 2.55%). Over different almond varieties, 6-year-old 'Nonpareil' trees intercepted more fPAR than others, which is reasonable because of their larger canopy size (up to 73% fPAR). Figure 4B visualized a similar calibration for 'Nonpareil' only with a better R2 of 0.96 and a lower RMSE of 2.06% to the 1:1 line (the difference was significant as shown in Table 3). This improved correlation might be due to the uniformity of the tree canopy from a single variety (mean of absolute errors to the regression line: 1.58 +- 1.00%; to the 1:1 line: 6.59 +- 2.47%). We scanned all three orchards using the aerial photogrammetry method within a day for each data collection from May to August. However, the lightbar method needed multiple days to complete the same tasks. Therefore, the VO method we offered in this study is practically easier and faster to conduct than a mobile lightbar platform to estimate canopy fPAR in the orchard environment.
Figure 5 shows the overall correlations of VO estimated fPAR over the growing season in 2019. We observed a good correlation among the data collected at different dates, with Pearson's r ranged between 0.92 and 0.99. Based on the scatter plots in the lower-left half, we could find better correlations when the two dates were closer. The highest Pearson's r of 0.99 was from the dates between July 26 and August 7. One possible reason could be the proximity of data collection dates (only 10-d difference). Besides, the histograms on the diagonal illustrate that all sampled trees were normally distributed, and the majority of the sampled trees were 'Nonpareil' and 'P16.013'. Lastly, the kernel-density-estimate plots in the upper right half show that the variations of VO estimated fPAR decreased from May to August with more data points aligned on the 1:1 line. Figure 5 illustrates the results of 12 different flights, image processing, and feature extractions conducted by the VO pipeline. High correlations in Figure 5 show the robustness and replicability of the VO methodology that consistently and accurately estimated fPAR in all 12 datasets. While we observed some canopy development over the season that leads to minor changes in the canopy profile, no major observational error (variation in measurement) was noticed for the same tree profile features measured during the season. To explore which method is more reliable, we further compared the VO and lightbar methods in estimating the actual almond yield from different spatial precision levels: per-row, per-block, and per-tree (VO only) level.
To test which method could better estimate actual almond yield, we compared the scatter plots of actual yield vs. canopy fPAR estimated by the mobile lightbar and VO methods on a per-row basis. Figure 6 summarizes the overall results, and Figure 7 shows more details in Supplementary Material. The results indicated that canopy fPAR estimated by VO is a more accurate indicator of almond actual yield than lightbar. Both R2 and predictive R2 are higher with the VO method (0.37 and 0.34 for VO; 0.34 and 0.31 for lightbar) on June 26. Both regression lines in Figures 7B,E had similar slopes (32 for VO; 36 for lightbar) and intercept on the y-axis. We may accept either method since both RMSEs were lower than the standard deviation of the actual yield (484.14 lb acre-1) with all varieties. We did not find any statistical difference between the means of absolute errors in predicting actual almond yield by the VO and mobile lightbar models. So, the VO method is statistically as good as the lightbar measurement but with potentially better performance as the VO models presented insignificantly smaller errors. One possible reason might be the higher spatial resolution of the VO method (0.01-0.02 m) compared with the mobile lightbar (~0.4 m). In general, the R2 of 0.34 estimated by the lightbar in our study agreed with the findings from Zarate-Valdez et al., who reported that mobile lightbar estimated midday fPAR was an indicator of almond kernel yield with R2 in the range of 0.16-0.36. A better correlation between VO estimated fPAR suggested that light interception, or fPAR, is not only a good indicator of potential (maximum) yield but also a possible good estimator of actual yield for almond (particularly the 'Nonpareil' variety).
We conducted separate analytics for 'Nonpareil' since it is the leading and most profitable almond variety in California. Results indicated better fits for both models if we only analyze the 'Nonpareil' variety. For example, we achieved a better R2 of 0.83 and predictive R2 of 0.79 for the 'Nonpareil' yield prediction than the model for all varieties (0.37 and 0.34, respectively). One reason might be that the sampled trees are more uniform when we tested with only one variety. This better performance on the 'Nonpareil' variety is also valid for using lightbar estimated midday fPAR. However, the achieved R2 (0.70) and predictive R2 (0.65) are notably lower than those from VO. Pearson's r followed a similar pattern. RMSEs for both methods with 'Nonpareil' only were lower than the standard deviation (497.64 lb acre-1) of actual almond yield at the per-row level. However, the RMSE of VO estimated fPAR (199.26 lb acre-1) was notably smaller than the mobile lightbar (265.73 lb acre-1) in June. These results reiterated the possibility that fPAR alone could be an accurate indicator of actual almond yield if it is estimated accurately. We may accept both VO and lightbar results in explaining 'Nonpareil' yield, but apparently, the result from VO seemed more accurate and reliable. Overall, we suggest that the VO method offers a more accessible and accurate (with smaller errors) alternative for estimating canopy fPAR than the mobile lightbar platform since the VO model showed a better correlation to actual yield. Therefore, we can use this VO technology as a reliable indicator for predicting actual almond yield, particularly with the 'Nonpareil' almond variety.
In addition to comparing VO estimated fPAR with lightbar data, we compared the yield prediction models based on data at a different time of the season. Interestingly, a descending trend of yield prediction accuracy is present from May to August when we tested all varieties (Figure 6). In other words, we found that we achieved a better actual yield prediction in May comparing to June, July, or August using VO estimated fPAR model for all varieties. The overall trend was in a reverse direction when we only tested 'Nonpareil'; the prediction accuracy on 'Nonpareil' improved as we got closer to the harvest time in August. This discrepancy of accuracy changes between all varieties and 'Nonpareil' suggests that a single comprehensive model cannot accurately predict yield for different almond varieties, and the yield prediction model should be calibrated for each variety. It might be more reasonable to develop models separately for each variety, such as 'Nonpareil', to explain the variations of actual almond yield.
The yield prediction accuracy with VO for 'Nonpareil' improved from May to June but did not change much after June 26. The source-sink interaction theory during plant growth may better explain it (Allen et al.,). Starting from the bloom in almonds (around February in a year), the reproductive growth (with reproductive organs: flower and fruit) is becoming more competitive with vegetative growth (with vegetative organs: branches and leaves) for absorbing the nutrients. Therefore, midseason (June/July) measurement might be more accurate for predicting actual almond yield when both growths are dominant. This deduction was verified because the midday fPAR was mostly measured with a lightbar system in midseason (June and July) for almond orchards (Lampinen et al.,; Rubke,). Lastly, the similarity of actual yield prediction results on June 26 between the lightbar (R2 = 0.34 for all varieties; R2 = 0.70 for 'Nonpareil' only) and VO method (R2 = 0.37 for all varieties; R2 = 0.83) also verified the strong correlation between these two methods of fPAR measurement as discussed earlier.
It was also interesting to notice that the regression lines (dashed blue line in Figure 8) had a smaller angle to the 1:1 line for 'Nonpareil' than all varieties combined in Figure 7. First of all, all data points (at the per-row level in Figure 7) were below the 1:1 line, indicating that none of the samples reached the potential yield in this study. Specifically, with the increase of estimated fPAR on the x-axis (0-100%), the slope of the regression lines moved farther (35.6 in Figure 7A to 29.0 in Figure 7D) from the potential yield line over the season for all varieties, suggesting that the actual yield prediction became less accurate. Comparatively, the regression lines directions were closer to the 1:1 line for 'Nonpareil' only (Figures 8A-D). Although the actual yield of 'Nonpareil' was also far less than the potential yield, the changing patterns were more comparable. We believe that the proposed model could be used as a good yield forecasting tool for 'Nonpareil' trees with an acceptable accuracy of R2 = 0.84 and RMSE = 195 lb acre-1 at the per-row precision level, where the standard deviation of the yield (498 lb acre-1) was about 2.5 times greater than RMSE. Besides, we analyzed the VO estimated fPAR with higher spatial precision (at the per-tree level) in the next section, but no corresponding lightbar data at this level of precision was available for comparison.
Figure 9 visualizes the regressions between per-tree fPAR (estimated by VO) and almond kernel yield over the season in 2019. Figure 10 provides in-depth details. As discussed for the per-row level results, the accuracy (R2) decreased for all-varieties-model from May (May 28; with R2 of 0.31 and RMSE of 504.88 lb acre-1) to August (August 7; with R2 of 0.24 and RMSE of 532.37 lb acre-1). The result at the per-tree level had a relatively poorer R2 (0.29), and RMSE (514.31 lb acre-1) with a greater standard deviation of the yield (609.38 lb acre-1) compared with the per-row analysis (R2 = 0.37 and RMSE = 38.18 lb acre-1 for VO; R2 = 0.34 and RMSE = 389.49 lb acre-1 for lightbar; the standard deviation was 484.14 lb acre-1) in June. This result is reasonable because we expected a greater variation in the dataset for the high-spatial-precision level of per-tree data. For instance, we observed a huge range of yield from 10.81 to 5094.49 lb acre-1 at a per-tree precision level. Given this large variation in per-tree yield data, VO estimated fPAR still offered a reasonable accuracy with higher spatial precision than lightbar data, which is mainly available at the per-row level.
When we only considered the 'Nonpareil' variety, we observed an increasing trend in accuracy (R2) similar to the per-row models (Figure 6). On July 26, the R2 was up to 0.62, and RMSE was 351.25 lb acre-1 for the 'Nonpareil' per-tree yield prediction. As expected, these results were not as good as the per-row model (R2 = 0.84 and RMSE = 195.01 lb acre-1). The RMSE from per-tree data were also much greater than that from per-row data due to the more diversity in the yield data. The differences were only significant between the two scenarios (i.e., all varieties and 'Nonpareil') when we tested the means of absolute errors using ANOVA (p < 0.05). In general, we conclude that the VO method provides an acceptable yield prediction accuracy (R2) at the per-tree level; a level of spatial precision in yield forecasting that has not been offered by the mobile lightbar platform or any other yield prediction methodologies.
It was important to note that more scattered points were getting closer to the potential yield line (Jin et al.,) due to the more variation in per-tree yield data. Two 'Monterey' trees (in yellow "x" symbol) yielded (5094.49 and 3801.04 lb acre-1) more than their potential yields (i.e., the two symbols were above the potential line in Figures 10A-D). Jin et al. found that the variation of the almond yield gap from actual yield to the potential yield (pass or not reach) was mainly driven by tree age and other factors if the orchards were located in different geographical areas. Since our three orchards were located close to each other, and all trees were mature, this gap was probably triggered by different orchard management and practices.
Orchards 1 and 3 contain several blocks in each row, consisting of three to eight trees based on the orchard configuration. Therefore, we also analyzed the data based on the per-block level, where the lightbar data were available to compare. Figure 11 compares the accuracies (R2) of the different measuring levels [per-tree (VO only), per-block, and per-row] in explaining almond actual kernel yield on June 26. In general, as the precision level decreased from per-block to per-row, the accuracy (R2) increased for both methods. For example, R2 increased from 0.29 to 0.37 using VO estimated fPAR in June. We expected this trend since the dataset contained more errors or extreme values when the precision level was higher. Subtle changes, such as a tree being shaded from neighboring trees, can cause biased data collection. We observed that even with the highest level of precision (at the per-tree level), the VO method achieved better accuracies (R2) than that of lightbar at a lower level of precision (at per-block level) for all varieties (R2 = 0.29 for VO at tree level; R2 = 0.23 for lightbar at block level). In other words, VO estimated fPAR could better explain the actual kernel yield with both higher accuracy and spatial precision than lightbar. Regarding 'Nonpareil', the per-tree VO method (R2 = 0.59) performed only slightly worse than the lightbar at the per-block level (R2 = 0.64). Overall, we can conclude that the correlation (R2) between the two measures (i.e., VO and lightbar estimated fPAR) can be up to 0.96, in which the VO method even better explained the almond actual kernel yield with up to 0.83 of R2 on the leading variety of 'Nonpareil' in June. The estimation accuracy was further improved for 'Nonpareil' toward the end of the season using the VO data.
In future work, we will consider adopting the DSM model generated by the LiDAR sensor instead of RGB photogrammetry, where LiDAR has much higher pixel resolutions. It is expected that fractional absorbed PAR (fAPAR) is highly correlated to fPAR due to fAPAR is strongly correlated to transmittance. In the PAR domain, the fAPAR is very close to the fPAR, corresponding to the canopy transmittance in the sun direction (Todd et al.,). Although only fPAR was considered in this work, we already tested the relationship between accumulated PAR (in the unit of mole) and fPAR using some preliminary datasets, where sun angle and sunlight directions were precisely modeled from sunrise to sunset at the specific locations of almond orchards. Per accumulating the total PAR over the entire growing season (four months from April 1 to July 31), we achieved a very high correlation (R2 = 0.97-0.99) between accumulated PAR and fPAR. Such information and results are out of the scope of this work and, therefore, will be presented in our future publications. We will also take the nitrogen and irrigation scheduling effects on the plants into account when we evaluate the correlation between estimated fPAR and almond yield. Besides, we will consider employing spectral reflectance (Moghimi et al.,) to determine tree nitrogen status and to better explain the yield variations in trees of similar size. | aerial photogrammetry, canopy light interception, canopy profile feature, digital elevation model, digital surface model, virtual orchard | Not supported with pagination yet | null |
PMC5779784_01 | Female | 20 | A 20-year-old woman was admitted to our hospital for weakness, numbness, and pain in the limbs for 6 months and worsened for 3 days. The patient felt persistent pain in the neck, left shoulder, and the upper left arm 6 months before, and the situation became worse and both upper extremities were affected. The patient visited the local hospital and was diagnosed as myelitis and she received gamma globulin (20 g for 5 days) and dexamethasone (5 mg for 15 days). Her symptoms were improved gradually. However, 1 month later, the weakness, persistent numbness, and pain in both lower extremities occurred again and gradually worsened with time. Therefore, the patient returned to the local hospital, and received vitamin B12 treatment, her symptom became slightly better but not completely recover. Six days before the admission to our hospital, the patient had symptoms of sneezing nose. Three days later, the patient had severe weakness and numbness in the lower extremities. Her past medical history was otherwise negative except for PTB for 6 years. At that time, the patient received systematic anti-tuberculosis treatments and her symptoms were completely disappeared and chest computed tomography (CT) showed chronic pulmonary tuberculosis.
Neurological examination revealed decreased muscle strength of both lower extremities (1/5 of the right extremity and 3/5 of the left extremity according to the Medical Research Council [MRC] grade) with bilateral hyperreflexia. Bilateral Babinski sign were positive. Hyperalgesia was found below the level of T8, deep sensation of the right lower limb was absent. The Expanded Disability Status Scale (EDSS) of the patient during hospitalization was 6.5. The magnetic resonance imaging (MRI) scan of the cervical spine (6 months before admission) revealed cervical spinal cord lesions without gadolinium enhancement (Fig. 1). The serum anti-AQP4-Ab was strongly positive, and the Immunoglobulin G (IgG) oligoclonal bands were negative both in the serum and in the cerebrospinal fluid (CSF). CSF routine test showed elevated protein levels (0.39 g/L, normal range from 0.15 to 0.45 g/L) and increased cell numbers (leukocyte count 25 x 106/L, normal range from 0 to 8 x 106/L), of which 92% were monocytes. Autoimmune diseases related test including anti-nuclear antibodies, anti-dsDNA, anti-streptolysin, rheumatoid factor, thyroid function tests, erythrocyte sedimentation rate (ESR), and hypersensitive C-reactive protein were all negative. T cell spot tuberculosis (TB) testing was positive. No tubercula bacilli were found in sputum TB smear. Anti-TB antibodies of Lipoarabinomannan-IgG and 38 KD/IgG in the serum were positive. Quantitative detection of Brucella polymerase chain reaction was negative in the CSF. Brain MRI after admission demonstrated multiple patchy abnormal signal in pons, the right thalamus, the left basal ganglia, corona radiate and corpus callosum on fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and T2-weighted (T2W) imaging (Fig. 2). The second MRI scan of cervical and thoracic spinal cord after admission to the hospital revealed hyperintensity lesions extending from C3 to T8 on T2W image, T1-weighted (T1W) image, and FLAIR image (Fig. 3A-C). Chest CT during hospitalization showed left lung upper lobe bronchiectasis and multiple calcifications of upper lobe in both sides (Fig. 3D). The patient was treated with methylprednisolone of 500 mg for 3 days, afterwards, the dose of methylprednisolone was decreased to half every 3 days, meanwhile she also received gamma globulin and anti-tuberculosis drugs (isonicotinyl hydrazide 0.3 g/d, rifampin 0.45 g/d, pyrazinamide 1 g/d, and ethambutol 1 g/d). The patient discharged from hospital after 1 months' treatment. The EDSS was decreased to 0 at the time point of follow up 12 months later. The spinal cord MRI showed the lesion size in the cervical and thoracic spine were significantly reduced (Fig. 4). | null | MRI scans of case 1 before treatment showed hyperintensity lesions in the spinal cord from C3 to T8 on T2 sequence Chest CT scan showed bronchitis and pneumonia in both sides, bronchiectasis in the left upper lobe and multiple calcifications of in both upper lobe (D). CT = computed tomography, MRI = magnetic resonance imaging. |
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PMC5779784_02 | Female | 21 | A 21-year-old woman was admitted to our hospital for numbness in bilateral lower limbs and in the chest for 7 days. She had a past medical history of PTB without receiving any treatment for 3 years. On neurological examination, the muscle strength in the upper limbs and lower limbs were 5/5 according to the MRC grade. Hyperreflexia was found in bilateral lower limbs. She was found loss of sensation of pain and touch in the spinal segments below T4. Bilateral Babinski sign were positive. Four days after admission, the muscle strength in bilateral lower limbs were 4/5 according to the MRC grade, with retention of urine. The EDSS of the patient was 4.5 during hospitalization. The MRI scan during hospitalization of cervical and thoracic spinal cord revealed diffuse hyperintense signal extending C3 to T11 on T2W and FLAIR images and hypointense signal on T1W images (Fig. 5A-C). The MRI of the thoracic spinal cord revealed altered medullary signal intensity from C6 to T11 levels, appearing hyperintense on T1W and T2W images (Fig. 5B). The chest CT showed left upper lobe tuberculosis with cavitation (Fig. 5D). CSF routine test showed increased protein levels (0.48 g/L, normal range from 0.15 to 0.45 g/L). The CSF cell numbers were within the normal range (4 x 106/L). The anti-AQP4-Ab was negative both in the serum and in the CSF of the patient. Tuberculosis mycobacterium antibody was negative both in serum and CSF. A combination of corticosteroid and anti-tuberculosis treatment (isonicotinyl hydrazide 0.3 g/d, rifampin 0.45 g/d, pyrazinamide 1 g/d, ethambutol 1 g/d, and dexamethasone 15 mg/d) was given. Neurological dysfunction was ameliorated significantly. The lesion size in the spinal cord and in the lung were significantly reduced 1 month later after discharge from the hospital. The EDSS of the patient dropped to 0 at the follow up time when 3 months after discharge from the hospital. | null | null |
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