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PMC5299169_01 | Male | 26 | A 26-year-old male (height: 1.93 m; weight: 95 kg) presented with neutral limb alignment, painful tibiofemoral kissing lesions, and severe knee OA-related activity limitations due to pain in the left knee of one-year duration (Kellgren-Lawrence grade 2) (Figure 1). The knee OA was contained to the medial compartment, and the patient had failed lifestyle/activity modifications, physical therapy, quadriceps strengthening, and analgesics. Preoperative passive range of motion was measured to 140 , and no hyperextension or flexion deformity was recorded. During the orthopedic examination, isolated medial tibiofemoral tenderness was observed. The following symptoms were all absent: patellar tap (no joint effusion), lateral tibiofemoral tenderness, anserine bursa, patellofemoral crepitus, and patellar grind. The ligaments and meniscus were stable. The patient reported mild, continual pain during walking but distance was not limited by the knee pain.
As a former professional league basketball player, the patient indicated a strong desire to return to an active lifestyle including more strenuous activities such as jogging, racquet sports, and basketball, which he was unable to take part in due to pain. After providing written informed consent, he participated in a clinical study that received ethics committee approval and was conducted in compliance with the Ministry of Health and Declaration of Helsinki. The left knee of the patient was treated with the Atlas System, and the patient was followed for a period of six months after surgery.
The Atlas System consists of a cylindrical, polycarbonate urethane (PCU) load absorber located between femoral and tibial bases (Figure 2). The device, located within the subcutaneous tissue on the medial side of the knee, is designed to reduce loading on the affected medial compartment of the knee joint, without transfer of loading to other areas of the joint. The device was inserted through a single incision, guided by direct visualization and palpation of the patient's anatomy. Following identification of the femoral medial epicondyle, adductor magnus tubercle, tibial plateau, joint space, and anterior border of the superficial medial collateral ligament through visualization and palpation, the tibial and femoral fixation points were located, and an absorber length was selected based on the patient's anatomy. A trial device was introduced via two K-wires, and implant function was confirmed through direct visualization checks. Following confirmation of function of the trial device, the final implant was introduced with the femoral base placed deep to the vastus medialis obliquus muscle and the tibial base placed distal of the deep medial collateral ligament and proximal to the insertion of the pes anserine. After installation of the final device, visual confirmation of functional unloading from full extension through deep flexion was performed prior to wound closure. No concomitant intra-articular surgery was performed to ensure that any benefit was due solely to the implant. Postoperatively, the patient was given crutches and told to bear weight as tolerated and to keep the wound protected for an initial 2-week period. Following stitch removal at 2 weeks, the 2-month rehabilitation protocol focused initially on range of motion and daily living activities, followed by muscle strengthening and endurance. | null | Not supported with pagination yet | null |
PMC5336929_01 | Female | 86 | An 86-year-old female patient with Parkinson's disease was admitted to a cardiology outpatient clinic for routine check-up. She had coronary artery bypass grafting 12 years ago. The patient was taking dabigatran 110 mg twice a day due to atrial fibrillation, metoprolol succinate 100 mg, perindopril 10 mg, atorvastatin 20 mg, and trimetazidine 35 mg twice a day. She was prescribed trimetazidine on account of chest pain unrelated to exertion 9 months ago. Electrocardiography revealed atrial fibrillation, with a heart rate of 74 per minute. Ejection fraction of 42% and moderate mitral regurgitation were detected on the echocardiography. Her effort capacity was too limited owing to Parkinsonism. Therefore, it could not be assessed whether exertional angina or dyspnea was present. A neurology consultation was recommended due to severe bradykinesia and postural instability during walking. However, it was ascertained that she had been on close follow-up by the neurology department for 7 months, and no significant clinical improvement was provided, even with dose increments of levodopa and, thereafter, addition of carbidopa and benserazide, respectively.
The patient's physical performance deteriorated in the last 7 months by virtue of accelerated progression of Parkinsonism. There was something bizarre in the patient's clinical status. She was doing well with only a moderate dose of levodopa, and it is questionable what happened and why she got worse rapidly. The physician was remembering an adverse effect of trimetazidine, which leads to extrapyramidal side effects. However, he was not quite sure whether trimetazidine could possibly cause it. After searching PubMed for adverse drug reactions of trimetazidine, case reports with Parkinsonism after trimetazidine use were detected. Trimetazidine was discontinued. After 3 months, the patient was taking only levodopa again, and the outcome was quite favorable after discontinuation of trimetazidine, with an almost full recovery to her past physical performance.
Trimetazidine is quite frequently used in cardiology practice as an anti-ischemic agent, albeit it might cause heartburn, nausea, and vomiting, as well as extrapyramidal side effects. The 2013 ESC guidelines on the management of stable coronary artery disease revealed a contraindication of trimetazidine in patients with Parkinson's disease.
As a cardiologist, we should learn all adverse effects of drugs that we are using in our daily cardiology practice, as well as pharmaceutical effects we already know well. This case teaches cardiologists to prescribe trimetazidine exactly when it is needed, and it may lead to Parkinson-like side effects, even in patients without Parkinson's disease. There is a main principal precept of bioethics that all medical students are taught in school: primum non nocere. | null | Not supported with pagination yet | null |
PMC9177335_01 | Male | 56 | A 56-year-old male, with irritability, aggression, suspiciousness, and sleep disturbances for 1.5 years, presented to psychiatric emergency services after an acute exacerbation. He had a history of irregularly treated type 2 diabetes mellitus and hypothyroidism. Two years earlier, the patient had developed low-grade fever, cough, and weight loss and then diagnosed as pulmonary TB. After three months of anti-TB treatment (ATT), he developed episodes of altered sensorium and generalised tonic-clonic seizures secondary to hyponatremia and normal pressure hydrocephalus, which resolved with conservative treatment (Table 1). One month later, the patient had recurrent dizziness, nausea, and vomiting. Evaluations revealed episodic hyponatremia and reduced serum cortisol. The patient could not afford further investigations. Considering pulmonary TB and physical signs of adrenal insufficiency, tubercular adrenalitis was provisionally diagnosed and empirical steroid treatment was initiated. Poor compliance to steroids resulted in a relapse of adrenal sufficiency along with an acute-onset, continuous course of psychiatric illness characterized by irritability, suspiciousness, and biological and sociooccupational dysfunction leading to the current clinical presentation. His premorbid, past, family, and substance use history were nil contributory. Mental status examination revealed delusions of reference, persecution, and misidentification. The patient was diagnosed with organic delusional (Schizophrenia-like) disorder (F06.2) as per the International Classification of Diseases-10th edition (ICD-10).
Psychosis improved with risperidone (2 to 6 mg/day) (Brief Psychiatric Rating Scale scores: baseline-58 and follow-up-32) over 2-3 months. His adrenal insufficiency was symptomatically managed with an endocrinologist liaison and reinitiation of steroid therapy. Adherence was ensured through telepsychiatry services. Written informed consent was obtained from the patient and caregiver prior to the write-up of this report. | null | Not supported with pagination yet | null |
PMC9662106_01 | Male | 67 | Our case, 67-year-old man, chronic smoker, known hypertensive, was on oral anticoagulation (apixaban) for paroxysmal atrial fibrillation. He was diagnosed with chronic kidney disease in 2019 and was on conservative treatment until March 2020 when he was instituted on hemodialysis via an uncuffed right internal jugular venous catheter. He opted for peritoneal dialysis and chronic ambulatory peritoneal dialysis (CAPD) was initiated after 2 weeks of peritoneal catheter insertion. Eight months later, he had COVID-19-related pneumonia but recovered with supportive care. In March 2021, he was referred to the emergency room (ER) for intractable chest pain radiating to the right side of the chest. On physical examination, he had pallor, minimal pedal edema, and a group of matted jugular lymph nodes with rubbery consistency and a stony hard right supraclavicular lymph node. High-resolution computed tomography (CT) chest was performed that suggested a mass in the right lower lobe that was locally invading the mediastinum and large filling defects (2.3 cm*3 cm) were observed in the left atrium suspicious of tumor thrombi extending into the right pulmonary vein (Fig. 1a, b). Magnetic resonance imaging (MRI) of the lumbosacral spine showed the tumor mass invading the seventh and the eighth vertebral foramina causing nerve compression. He underwent a true cut biopsy of the right supraclavicular lymph node and simultaneous CT-guided biopsy of the lung mass. Histopathological examination of the jugular node showed epitheloid cell granuloma, along with rare giant cells with focal necrotic debris with an overall picture suggestive of tuberculosis. His biopsy of the lung mass was suggestive of a non-small cell lung cancer. Transesophageal echocardiography (TEE) was performed which showed a large oscillatory mass (2.5*3.0 cm) attached to the upper right pulmonary vein and extending into the left ventricle through the mitral leaflet. The patient was started on anti-tuberculosis treatment and planned for radiotherapy followed by chemotherapy as the tumor deemed surgically inoperable due to stage IV disease (T4) and active tuberculosis. The patient developed sudden onset confusion and dysarthria; MRIhead showed an acute infarct in the left frontal area and the anti-platelets and statins were added to the ongoing anticoagulation. Palliative radiation with Volumetric Modulated Arc Therapy (VMAT) technique was planned for 40 Gy in 15 fractions. The patient could complete 8 out of the 15 planned sessions as after the eighth session he became comatosed and the repeat diffusion-weighted MRIhead showed multiple acute infarcts bilaterally present in the fronto-parietal and temporo-occipital region, basalganliothalamic regions, cerebellar hemispheres, and cerebral vermis (Fig. 2a-c). Patient in view of poor sensorium got intubated the same day and later suffered a cardiac arrest and could not be revived. | cardiac invasion, case report, embolic shower, lung cancer, malignant stroke | Not supported with pagination yet | null |
PMC9868268_01 | Male | 47 | A 47-year-old male was hospitalized on February 4, 2022, presenting with recurrent diarrhea for more than 7 months and with a fever for 5 days (highest temperature of 38.3 C). The patient reported about five yellow watery stools per day, accompanied by nausea, abdominal distension, and poor appetite. The patient had a weight loss of more than 10 kilograms in 6 months. The source of this patient's microsporidium infection was unclear. For the past year, his travel had been limited to Guangdong Province in China. He was diagnosed with B-ALL in July 2019. He had previously received more than 10 antileukemia combination chemotherapies following the modified Berlin-Frankfurt-Munster 90 (BFM-90) protocol for acute lymphoblastic leukemia, beginning in March 2020 with long-term oral methotrexate (MTX, 20 mg/m2, once a week) and 6-mercaptopurine (6-MP, 50 mg/m2, once a day) as maintenance chemotherapy. Approximately 1 month and 6 months after the initial symptoms of diarrhea, the patient underwent colonoscopy and gastroscopy, respectively, which showed no obvious abnormal lesions. During the period of diarrhea, repeated culture and routine detection of stool, several bone marrows punctures and a positron emission tomography/computed tomography (PET-CT) examination were performed, and no evidence of tumor recurrence was found.
At admission, the patient was dehydrated and had abdominal distention and pain; taking MTX and 6-MP at the time. Laboratory analyses showed lymphocytopenia (0.103x109/L), with macrocytic and moderate anemia (hemoglobin concentration was 86 g/L, the mean erythrocyte volume was 113 fl), C-reactive protein level was 148 mg/L, procalcitonin was 0.272 ng/ml. His CD4 and CD19 counts were 31 cells/microl (24.3%) and 5 cells/microl (4%) in the peripheral blood, respectively. Stool routine, urine routine, stool culture, urine culture, blood culture, Widal test, waffian reaction, anti-nuclear antibody, anticardiolipin antibody, antineutrophil cytoplasmic antibody, G and GM test, T-spot TB test, EB virus, and cytomegalovirus DNA were all negative. The smear of the stool followed by Wright's stain had also been performed, and a small number of spores were observed under a light microscope, but it could not confirm the species of spores. The liver and kidney functions were normal and the albumin level was 19.1 g/L. Bone marrow smear and flow cytometry examination showed no abnormalities.
Physical examination revealed that the patient had an unwell and anemic appearance, unpalpable superficial lymph nodes, abdominal distention, abdominal muscle tension, tenderness, shifting dullness, and slight edema of the lower limbs. The cardiopulmonary examination was unremarkable.
Based on these tests above, the diagnosis of local or systemic bacterial, viral, fungal and tuberculosis infection was not supported, nor was the evidence of tumor recurrence.
The patient immediately stopped taking oral chemotherapy for leukemia, was first administered piperacillin/tazobactam, amikacin and caspofungin, and was treated symptomatically with intravenous fluids, antidiarrheal, probiotics, folic acid and vitamin B12. Fever still occurred 5 days after treatment, the highest temperature was 38.4 C, and his diarrhea remained uncontrolled (approximately 5 liquid bowel movements per day). Abdominal distension, abdominal pain, and other related symptoms did not improve. Routine blood and biochemical examinations showed no apparent changes.
Due to a lack of response from the previous antibiotic treatment, the patient underwent another full-body PET-CT, which revealed elevated glucose metabolism throughout the peritoneum (standardized uptake value (SUV) max=12.57) and part of the penis (SUVmax=13.41) and massive peritoneal effusion with peritonitis, suggesting tumor or microbial infiltration ( Figure 1A ). Then,
We performed peritoneal puncture drainage on the patient, peritoneal fluid was obtained from the patient for mNGS testing. E. bieneusi genomic sequences were detected, suggesting a likelihood of infectious disease. The sequencing results were obtained within 24 hours, which revealed E. bieneusi DNA sequence reads was 85, the RNA sequence reads was 3495,the DNA sequences covered 0.20% of the genome ( Figure 2A ), the RNA sequences covered 2.21% of the genome ( Figure 2B ). Meanwhile, target gene sequencing and mutational analysis showed no tumor-specific or germline mutations.
The patients were evaluated using 475 Lymphoma-related NGS panel. DNA extraction, sequencing library preparation, and targeted capture enrichment were carried out following the methods as previously described with modifications. Target enriched libraries were sequenced on the HiSeq4000 platform (Illumina). Single-nucleotide variants, indels, structural variants, and copy number changes were identified by validated bioinformatics process from paraffin-embedded tissues. Mutant allele frequency (MAF) cutoff for single-nucleotide variants and indels was defined as 1%. The log2 ratio cut-off for copy number gain was defined as 2.0 for tissue samples. A log2 ratio cut-off of 0.6 was used for copy number loss detection.
The DNA of ascitic fluid extracted using the TIANamp Magnetic DNA Kit (Tiangen) according to the manufacturer's protocols. DNA libraries were prepared using the KAPA Hyper Prep kit (KAPA Biosystems) according to the manufacturer's protocols and were 75bp single-end sequenced on Illumina NextSeq 550Dx (Illumina). We use in-house developed bioinformatics pipeline for pathogen identification. Our microorganism genome database contained bacteria, fungi, virus and parasite genomic sequences (download from ).
We used the following criteria for positive results of mNGS:
For Mycobacterium, Nocardia and Legionella pneumophila, the result was considered positive if a species detected by mNGS had a species-specific read number>=1. For bacteria (excluding Mycobacterium, Nocardia and Legionella pneumophila), fungi, virus and parasites, the result was considered positive if a species detected by mNGS had at least 3 non-overlapping reads. Pathogens detected in the negative 'no-template' control (NTC) were excluded but only if the detected reads was >=10-fold than that in the NTC.
We attempted to treat the patient with albendazole at 400 mg twice daily for 7 days (14 February to 20 February 2022). The patient became weaker and continued to have severe diarrhea with worsening abdominal distension and pain. Bedside abdominal ultrasound indicated that there was still a large amount of ascites, and more separation bands were visible, which resulted in no peritoneal fluid draining from the abdominal drainage tube. Albendazole tablets probably failed to produce a clinical reaction.
After a review of extensive literature, alternatively, the patient took nitazoxanide (500 mg twice a day for 14 consecutive days) with reported successful treatment in case reports with AIDS and solid tumors after organ transplantation. About three days after the above treatment, his stool began to form and the frequency decreased; he presented no nitazoxanide-related side effects and was discharged home. The patient completed fourteen days of nitazoxanide. A full-body PET-CT was performed more than one month later, which showed a decline in glucose metabolism throughout the peritoneal and penile regions; meanwhile, the ascites had completely resolved ( Figure 1B ). His CD4 count increased to 297 cells/microl (26.3%) in peripheral blood, and his hemoglobin level was normal. He was successfully treated with nitazoxanide, and the clinical symptoms disappeared.
At the recent follow-up, the patient had no anemia, no fever, no diarrhea, no abdominal pain, no abdominal distension, a normal diet, and sleep. A whole-body contrast-enhanced CT was also obtained on July 11, 2022(approximately 5 months after treatment for Microsporidia), which also showed no abnormalities. Considering that the maintenance treatment of the patient's leukemia was almost over, the patient was instructed to review the signs and examinations related to leukemia regularly. | enterocytozoon bieneusi infection, case report, leukemia, metagenomic next-generation sequencing, nitazoxanide | Not supported with pagination yet | null |
PMC5602126_01 | Male | 22 | In May 2012, a 22-year-old man presented to our clinic with a 2-month history of a visual field (VF) defect over the temporal side of his right eye. He did not have a history of systemic disease. At the first ophthalmic examination, the best corrected visual acuity (BCVA) of each eye was 20/20. Both pupils were 6 mm, round, and reactive to light without a relative afferent pupillary defect. The intraocular pressure was 11 mmHg in the right eye and 8 mm Hg in the left eye. There was no anterior uveitis or conjunctival granulomas in either eye. Funduscopic examination revealed bilateral swelling of the optic discs, a grayish-white mass in the superotemporal peripapillary region between the disc and fovea, and hard exudates around the fovea in the right eye (Fig. 1). Fluorescein angiography (FA) revealed optic disc staining in both eyes (Fig. 2). Automated static perimetry revealed a substantially enlarged blind spot of the right eye, which was compatible with the clinical symptom and fundus examination (Fig. 3).
The complete blood cell count and the serum biochemical profile were unremarkable, and a blood culture for bacterial and fungal pathogens was negative. Acid-fast stain and tuberculosis sputum culture were also negative. The serology test results were negative for human leukocyte antigen B27, antinuclear antibody, rheumatoid factor, reactive plasma reagin, human immunodeficiency virus antibodies, and toxoplasmosis antibodies. Immuno-globulin M antibody levels for cytomegalovirus herpes simplex virus, and varicella-zoster virus were normal. Magnetic resonance imaging of the brain was performed with contrast. There was no space-occupying lesion in the brain or midline shift of the brain supratentorially or infratentorially. Radiographs and computed tomography (CT) images of the chest revealed multiple enlarged and confluent nodes (maximal dimension, >7 cm) at multiple compartments of the bilateral mediastinum, bilateral hilar region, and neck region. This finding was suggestive of sarcoidosis. The differential diagnosis included lymphoma (Fig. 4). Therefore, an ultrasound-guided biopsy of a cervical lymph node was performed. The histopathologic evaluation of the sample revealed granulo-matous tissue without caseous necrosis, which stained negatively with cytokeratin (CK). Therefore, a diagnosis of lymphoma was excluded (Fig. 5). The patient was diagnosed as having neuro-sarcoidosis, based on the presentation, clinical testing, and biopsy results. Treatment was initiated with corticosteroids. After retrobulbar injection of triamcinolone 1.5 mL (10 mg/mL) into the right eye and systemic treatment with oral prednisolone (15 mg 3 times daily; total, 45 mg/d) for 3 months, the patient's optic disc and macular lesions improved (Figs. 6 and 7). Approximately 1 month later, the VF defect resolved (Fig. 8). | biopsy, optic disc edema, sarcoidosis | Chest computed tomography reveals multiple enlarged nodes in multiple compartments of the bilateral mediastinum and the bilateral hilar region (red arrows). |
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PMC10440502_01 | Female | 8 | An 8-year-old female, with no significant past medical history (PMH), presented to the Emergency Department (ED) for evaluation of 1-month painful left inguinal lymphadenopathy. A 6-month-old kitten had scratched her legs prior to symptom onset. She had experienced fever and night sweats over 2-3 weeks. Blood tests, collected 2-3 weeks into illness, were significant for Brucella immunoglobulin M (IgM) positive, Brucella immunoglobulin G (IgG) negative, Bartonella serologies negative, Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) serologies negative, and tuberculosis (TB) quantiferon gold negative. At ED presentation, she had already completed 5 days of cephalexin, 10 days of clindamycin, and 5 days of azithromycin.
Fever recurred at time of ED presentation. Physical exam was significant for bilateral inguinal and right submandibular lymphadenopathy. COVID-19 test was positive. Notably, total Brucella antibody was negative. Bartonella henselae IgG and IgM were positive (IgG >1:1024, IgM 1:256). Fever and elevated inflammatory markers were attributed to COVID-19 infection. Supportive care was continued without further therapy, as patient had already completed 5 days of azithromycin. At 1 week follow-up, lymphadenopathy persisted with mild tenderness. | bartonella henselae, cat scratch disease | Not supported with pagination yet | null |
PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-C) First HRCT - interstitial pneumonia, air bronchogram, pleural effusion. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-C) First HRCT - interstitial pneumonia, air bronchogram, pleural effusion. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-C) First HRCT - interstitial pneumonia, air bronchogram, pleural effusion. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-E) Control HRCT - normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-E) Control HRCT - normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-E) Control HRCT - normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-E) Control HRCT - normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. |
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PMC4319657_01 | Unknown | 4 | Following a 4-day stay at the detox ward, a 20-year-old patient with a 5-year-long addiction to marijuana, a history of nicotinism and alcohol dependence, inhaling the so-called artificial hashish for 6 months was admitted to the lung disease department in serious condition with a suspected miliary tuberculosis. On admission, the physical examination demonstrated single bilateral rhonchi and rales over the lung fields, tachypnea, general cyanosis, and saturation of 65-72%. The patient reported catarrh lasting for 6 months; cough lasting 4 months, which was stronger for a week and a half preceding admission to hospital, 4 days of fever, diarrhea and dyspnea at rest. The patient denied hemoptysis or contact with tuberculosis.
Laboratory tests showed hypoxemic respiratory insufficiency, high titres of CRP, LDH, d-dimers, and NT-pro-BNP. Infection with HIV and HBV was excluded.
Oxygen therapy with 6 L/min of Encorton at a dose of 1 mg/kg body weight p.o., Clexane s.c. and antimycobacterial drugs were used.
Imaging examinations were ordered.
Chest X-ray showed diffuse, confluent interstitial changes of the highest intensity in the middle and inferior fields, and trace of pleural effusion. Besides, the image was unremarkable.
First HRCT showed massive generalized shading with air bronchogram in the middle and inferior fields, heterogeneous patchy changes in the superior fields. Complicated interstitial pneumonia with little pleural effusion was suggested.
Bronchofiberoscopy showed features of active inflammation of the bronchial tree.
Only Candida albicans was grown from cultures from bronchial washings; specific, non-specific flora and atypical pathogens (Bordatella pertussis, Legionella pneumophila, Mycoplasma pneumoniae, Pneumocistis jiroveci) cultures - negative.
Fluconazole p.o. was added to the above-mentioned therapy, which caused gradual clinical improvement.
A control chest HRCT performed after 3 weeks revealed normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. The whole image suggested toxic lung injury to differentiate with P. jiroveci infection.
After five weeks spent in the department, initial clinical improvement and reduced oxygen therapy to 3 L/min, spirometry with diastolic test was performed. The first examination result showed a decrease in VC to 84%, FEV1 89%, FEV 1%, VC 105% of due value. In the second test after administering Berotec: VC 82%, FEV1 94%, FEV 1%, VC 113% of due value. Basing on the results there was a suspicion of restriction. Due to insufficient co-operation with the patient, plethysmography confirming the diagnosis was not performed.
In the histopathological examination (material obtained from open biopsy), the image corresponded to organizing pneumonia with lipid bodies in the organizing lesions; lesions most likely caused by inhaling irritants. A biopsied mediastinal lymph node - reactive (Figures 1-4). | drugs, lung diseases, interstitial, lung injury, radiography, respiratory insufficiency | (A-E) Control HRCT - normal cavities, mediastinum and pleura, disseminated confluent small nodules of varying degrees of saturation, local frosted glass-like changes, which in the inferior fields coalesced with nodules of the central part of the pulmonary lobule and thickened interlobular septa. |
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PMC8034995_01 | Male | 65 | Mr. F, a 65-year-old male, was brought to the psychiatric outpatient clinic by his family who reported labile mood, impulsivity, decreased need for sleep, grandiosity, talkativeness, and increased goal-directed behaviors for 3 weeks. Several instances of physical aggression toward family members and self-harm were also reported. He also reported auditory hallucinations without visual hallucinations. A trigger event occurred one month previously, when his affairs were discovered by his family. He initially became depressed and anxious and then experienced mania, as mentioned above, a week later. The patient was oriented and communicable at the clinic despite his irritability. Late-onset bipolar I disorder was diagnosed, and a combination of valproic acid 500 mg/day and olanzapine 10 mg/day was prescribed for acute mania. The subsequent laboratory examination revealed balanced electrolytes, normal thyroid function, and negative syphilis rapid plasma reagin (RPR). Electroencephalography (EEG) showed mild diffuse cortical dysfunction.
The patient's condition improved gradually within the first week of psychiatric treatment. However, he became more agitated and paranoid thereafter, with aggravated auditory hallucinations and persecutory delusions. These symptoms did not improve despite titrating valproic acid to 1000 mg/day and switching from olanzapine to paliperidone 9 mg/day. He was hospitalized in the acute psychiatric ward, and his blood tests and chest X-ray were unremarkable.
In the first 2 weeks of hospitalization, the patient remained agitated and paranoid, and he was frequently placed in a seclusion and protection room (SPR) due to concerns about safety and maintaining his sleep schedule. With the medication adjustment, the patient's clinical condition improved gradually. He was discharged after 6 weeks of hospitalization; the discharge regimen was valproic acid 500 mg/day, aripiprazole 20 mg/day, and quetiapine 150 mg/day. Psychological tests before discharge were performed; the cognitive abilities screening instrument-2.0 (CASI-2.0) score was 82.5/100, and the clinical dementia rating scale (CDR) score was 0.5.
In the following 8 months, his mood remained stable and no psychosis was observed; therefore, the medication was gradually tapered to valproic acid 500 mg/day and quetiapine 50 mg/day. We performed brain magnetic resonance imaging (MRI) to exclude other physiological causes of late-onset bipolar disorder; the findings showed only old, small insults and atrophy. However, after remaining stable for another year, the patient developed acute cognitive function decline and an unsteady gait for 2 months. Laboratory blood tests were unremarkable, while cerebral positron emission tomography (PET) showed decreased [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake in the cortex regions, compatible with typical Alzheimer's disease. Psychological tests revealed a CASI-2.0 score of 73.4/100 and a CDR score of 0.5, so rivastigmine 9 mg was given. Despite the prescription of antidementia drugs, the patient experienced exacerbations of disorientation, paranoia, delusions involving theft, delusions involving jealousy, visual hallucination, irritability, negative thoughts, insecure feelings, and inappropriate behaviors. These symptoms were considered to be attributed to behavioral and psychological symptoms of dementia (BPSD).
One month later, a neuropsychological assessment was performed because of the presentation of severe clinical dementia, with a CDR score of 2 (Table 1). His rapidly declining cognitive function was alarming, but there were no remarkable neurologic deficits or physiological abnormalities at that time. Three months later, his family reported progressive left side extremity weakness and frequent choking for a week, so he was referred to the emergency room (ER) by the outpatient clinic. Laboratory blood tests were still unremarkable, but a chest X-ray showed a mass in the right upper lobe of the lung (Figure 1). Brain computed tomography (CT) and MRI revealed a mass lesion in the left occipito-parietotemporal lobe, sized 8.4 cm x 4.4 cm x 6.0 cm, with a midline shift to the right (Figure 2). Malignant origin was favored, and neurosurgery specialists were consulted for evaluation.
Given the concern about the effect of this large tumor and the rapid progression of neurologic deficits, the patient underwent emergency tumor removal surgery. The pathological report showed metastatic adenocarcinoma of pulmonary origin. Whole-body CT with a contrast agent revealed a necrotic lung mass in the right upper lobe and a solid lung nodule in the left upper lobe. FDG PET-CT confirmed right upper lung cancer with lung-to-lung and distant brain metastasis. The patient was then transferred to a pulmonary oncologist for chemotherapy.
The patient did not take any psychiatric medication after surgery; however, valproic acid 1000 mg/day was prescribed by the neurosurgery specialist for postbrain surgery seizure prophylaxis. | null | Not supported with pagination yet | null |
PMC8262157_01 | Male | 74 | A 74-year-old man who was married with a son and daughter was admitted because of intermittent mucoid discharge from his urethra and difficulty voiding for 3 years. Indwelling catheterization was performed because of urinary retention. Digital rectal exanmination revealed a suspicious soft cystic mass with an unclear boundary in the upper left area of the moderately enlarged prostate. Serum prostate-specific antigen (PSA) was 4.12 ng/ml. Imaging studies (Figure 1) and an endoscopic examination (Figure 2) were subsequently performed. Magnetic resonance imaging (MRI) detected an irregular cystic-solid mass with villiform long T1 and T2 signals in the left ejaculatory duct area. Vasography showed an incomplete cyst-like structure with a filling defect under the bladder. Cystoscopy disclosed a cystic cavity filled with mucoid substance and multiple papillary neoplasms, which opened into the prostatic urethra near the top of the verumontanum. The cystoscope could be inserted into the right seminal vesicle through the urethral opening. Biopsies showed that the neoplasm was a metastatic mucinous adenocarcinoma or tubulo-villous adenoma. Immunohistochemistry revealed it to be a mucinous adenocarcinoma. All gastrointestinal tract tumor markers were normal. Computed tomography (CT) scanning showed a cystic-solid mass occupying the left ejaculatory duct area without renal agenesis. Contrast agent revealed an obviously enhanced cyst wall and a papillary lesion at the junction of the sigmoid colon and rectum. Colonoscopy revealed a 2.0-cm polypoid mass in the proximal rectum. An endoscopic polypectomy was performed and the pathological result was a tubulo-villous adenoma. A radical prostatectomy and seminal vesiculectomy were then performed. The pathological diagnosis was adenocarcinoma with 55% mucinous adenocarcinoma (enteric-type). No lipochrome pigment granules were oberved in the tumor. Immunohistochemistry showed PSA (-), P504S (+), 34betaE12 (+/-), P63 (-), ERG (-), CK7 (+), CK20 (+), CDX-2 (3+), SATB-2 (-), CEA (-), AR (-), Ki-67 (40%+), PAX2 (-), PAX8 (-) and MUC6 (2%+) (Figure 3). | ejaculatory duct, ejaculatory duct adenocarcinoma, ejaculatory duct cyst, ejaculatory duct tumor, mucinous adenocarcinoma | Not supported with pagination yet | null |
PMC9639434_01 | Female | 4 | A 4-year-old HIV-uninfected girl was referred to the paediatric pulmonology clinic at Chris Hani Baragwanath Academic Hospital, South Africa (SA), with a 2-year history of chronic cough and poor weight gain. She had been treated with repeated courses of antibiotics for respiratory tract infections, and had also been started on tuberculosis (TB) therapy based on the chronic cough and abnormal findings on chest radiographs.
At presentation, she was stunted, had digital clubbing, and had dullness to percussion on the right side of the chest with reduced breath sounds. Her white cell count was raised (20.7 x 109 /L) with predominant lymphocytes (80.9%). The frontal chest radiograph showed a dense homogeneous opacification in the right middle and lower zones, and the left middle zone (Fig. 1). The lateral chest radiograph showed that the opacification was from the anterior mediastinum. Bronchoscopy showed a patent right upper lobe bronchus, but the right bronchus intermedius was completely occluded as a result of external compression.
The left upper and lower lobes were normal in structure with patent bronchi. A chest computed tomography (CT) scan (Fig. 2) showed an anterior soft-tissue hypodense mass on the right with herniation across the midline to the left hemithorax that displaced surrounding structures but was not encasing them. Histological examination of a Tru-Cut biopsy specimen showed benign thymic parenchyma with no evidence of neoplastic infiltration.
Sternotomy was performed and the entire mass was resected. The tumour was initially removed as a well-encapsulated bilobar mass, but the mass extended posteriorly into the right thorax and required some piecemeal resection (Fig. 3). Two large specimens were analysed, weighing 610 g and 360 g and measuring 170 x 100 x 30 mm and 120 x 60 x 20 mm, respectively. Microscopy revealed thymic parenchymal tissue mixed with mature adipose tissue, and no features of cytological atypia. Numerous Hassall's corpuscles were also seen. The final histopathology report confirmed that the tumour was a thymolipoma. There were no intra- or postoperative complications, and the patient was discharged. | giant thymolipoma, anterior mediastinal, respiratory symptoms, tumour | Not supported with pagination yet | null |
PMC5554400_01 | Unknown | 5 | Natural variation and diversity present in the language input of bilingual children may impact their vocabulary acquisition. In bilingual children, the quantity of input they receive is naturally divided between two languages, e.g., mother's vs. father's language, or L1 (i.e., home, heritage, or minority language) vs. L2 (i.e., community, or majority language). Thus, the nature of bilingual upbringing results in less input for each of the languages in comparison to the input received by monolingual peers (, but cf.). Reduced language input may be one of the reasons why bilingual children are repeatedly shown to score lower than monolinguals on vocabulary tasks in the majority language (e.g.,). Importantly, those vocabulary setbacks are found in different language pairs (e.g.,), across pre-school and school years, and - in the case of the majority language - are largely related to home-context vocabulary, rather than the school-context. A direct link between bilingual vocabulary development and language exposure was investigated by in a group of 5-year-old simultaneous French-English bilinguals in Canada3. Bilinguals' performance on receptive and expressive vocabulary was compared to that of their monolingual peers matched on age, socioeconomic status, and non-verbal intelligence, but differing in the amount of exposure they received in each language. A robust relationship was found between the amount of exposure to a language and children's performance in that language, although the relationship was observed to be different for the receptive and expressive vocabulary. Bilinguals exposed to both languages to the same extent scored comparably to monolingual children in the receptive vocabulary test, but they needed more input in a given language (and relatively less in the other one) to keep up with their monolingual peers in expressive vocabulary.
Access to many speakers of a given language seems to be another important factor contributing to language abilities in bilinguals. In a recent study by, the number of heritage language speakers that participants spoke to, correlated positively with their scores on a picture naming task (measured as the number of correct responses) in that language, and did not correlate negatively with their correctness in picture naming in English (community language). Importantly, the effect was independent of how frequently the participant used each language. Presumably, the greater the number of unique native speakers that a child interacts with on daily basis, the greater the variety of words used with a child, which may contribute to the child's vocabulary. | home language, minority language, multilingualism in migrant context, trilingual children, trilingual language acquisition, vocabulary acquisition | Not supported with pagination yet | null |
PMC8418048_01 | Male | 48 | A 48 years old Asian male diagnosed with type 2 diabetes mellitus two years back presented to our emergency with complaints of left-sided chest pain, radiating to back and dry cough for 25 days along with a low-grade fever of 99.8 F without any diurnal variation, relieved on medications for 20 days. There was no complaint of shortness of breath, orthopnea, abdominal discomfort, headache, or contact with a tuberculosis patient; however, he had a history of insignificant weight loss and loss of appetite for two months. He was on injectable human insulin (30/70) as 12 units subcutaneously before breakfast and eight units before dinner, and his blood dextrose level was uncontrolled since he reported positive for COVID-19 20 days back. However, he did not need hospitalization, steroids, or oxygen therapy and was managed conservatively in a COVID care center. The characteristic clinical, laboratory, and treatment profile of the patient have been tabulated in Table 1. On presentation, he had a blood pressure of 144/90 mmHg in the right radial artery, a random blood glucose level of 478 mg/dL with positive urinary ketones, a pulse rate of 89/min regular, and oxygen saturation of oxygen 98% under room air. General physical examination was unremarkable, and on chest auscultation, bilateral coarse crepitations were heard more over left interscapular and inframammary areas. An electrocardiograph was done, which showed normal sinus rhythm, and a portable bedside chest radiograph showed bilateral hilar prominence with a possibility of consolidation or a mass lesion (left > right), as shown in Fig. 1. A nasal and oropharyngeal swab for SARS-CoV-2 was taken, which was reported negative. The patient's arterial blood gas showed metabolic acidosis with a pH of 7.32, bicarbonate as 16.8 mEq/L, and normal partial pressure of oxygen and carbon dioxide. On presentation, a provisional diagnosis of newly diagnosed hypertensive with type 2 diabetes mellitus complicated by diabetic ketoacidosis and a lower respiratory tract infection with a query of perihilar mass was made. The patient's blood samples for routine blood parameters were withdrawn along with blood and urine cultures before starting intravenous antibiotics. On admission, blood parameters revealed a hemoglobin of 10.1g/dL, TLC of 13,400 cells/mm3, DLC of 91% neutrophils, 8% lymphocytes, platelets of 4.1 lakhs/mm3, ALT of 50 U/L, AST of 41U/L, LDH of 352 U/L, D-dimer of 497 ng/ml, INR of 1.14, IL-6 of 34 (<7pg/ml) and highly sensitive CRP of 212 mg/L. The patient had a normal renal function test, serum electrolytes, calcium, phosphate, total proteins, and serum albumin levels. As a result, treatment was started with empirical antibiotics as a piperacillin-tazobactam combination with levofloxacin along with strict blood glucose control with an insulin infusion and intravenous fluids. Subsequently, a Contrast-Enhanced Computed Tomography Angiography (CECT- Angio) of the chest was performed, which depicted findings consistent with Pulmonary Mucormycosis and bilateral ground-glass opacities in lower lobes without any evidence of pulmonary artery thrombosis, as shown in Fig. 2, and a normal transthoracic 2D-echo study. On the second day, as the patient recovered from diabetic ketoacidosis, injection liposomal amphotericin B (5-10mg/kg/day) at a dose of 300mg intravenously daily was added to the treatment with the aim of a total dose of 4 g along with strict monitoring of kidney function and serum electrolytes. Later, as the patient continued to have a low-grade fever and dry cough, a bronchoscope-guided bronchial biopsy of the left lower lobe mass was performed. Serial sections of processed tissue demonstrated large areas of necrosis and inflammatory granulation tissue along with aseptate branched fungal hyphae visualized as consistent with mucormycosis. However, an Acid-Fast Bacilli (AFB) stain was negative. As the patient continued to experience low-grade fever, injection vancomycin was added to the treatment because of an elevated serum procalcitonin level, i.e., 1.8 (>2ng/ml for high risk of infection), although his urine microscopy, blood and urine cultures were sterile after 48 hours of incubation. Peripheral smear for malaria antigen, serologies for HIV, hepatitis A, B, C, D, E, dengue, rickettsia, scrub typhus, Leptospira, beta 2 glucans, aspergillosis, galactomannan, and repeated urine routine microscopy, blood and urine cultures reported negative. The patient's blood glucose was taken care of by human (plain) intravenous insulin injections and intravenous fluids, and potassium supplementations. On the seventh day, he developed cough with expectoration, hence sputum for AFB, CBNAAT (Cartridge Based Nucleic Acid Amplification), gram stain, culture sensitivity, and fungal cultures were sent for analysis. On the ninth day, his sputum for AFB was reported positive. CBNAAT showed no rifampicin resistance; hence weight-based anti-tubercular therapy (ATT) (isoniazid 300mg, rifampicin 450 mg, pyrazinamide 1200mg and ethambutol 800mg) along with tablet pyridoxine 20mg were added further to the treatment. The patient started experiencing vomiting and abdominal pain on the eleventh day with deranged liver function tests (AST -127U/L, ALT-98, Total Bilirubin -1.7), hepatic modified ATT (injection streptomycin 0.75g daily, tablet ethambutol 800mg, and tablet levofloxacin 750 mg alternate day) was initiated. However, his abdominal ultrasonography was normal. On the thirteenth day, tab Posaconazole 300mg was also added to treatment. On the sixteenth day, he experienced right nasal congestion with blackish crusting of the nasal septum, a nasal swab for 20% KOH mount was sent, which showed aseptate branched fungal hyphae consisting of mucormycosis, as shown in Fig. 3. A CECT of paranasal sinuses and orbit was done, which showed findings of Sino-nasal mucormycosis, as shown in Fig. 2. Hence, a FESS (Functional Endoscopic Sinus Surgery) guided biopsy and local debridement were done, as shown in Fig- 3. However, on the twentieth day, the patient developed massive hemoptysis and went into hypovolemic shock. Hence, Ryle's tube was inserted, two packed cell volumes of blood were transfused along with inotropes, and the patient was planned for an emergency therapeutic bronchoscopy, however as the patient's GCS (Glasgow Coma Scale) deteriorated patient was electively intubated. Unfortunately, the patient succumbed to his illness on the very next day. Written consent was taken from the patient's relative to reproduce the clinical data. | bronchospopy, co-infection, haemoptysis, massive, post covid-19, pulmonary mucormycosis, pulmonary tuberculosis | Not supported with pagination yet | null |
PMC7225731_01 | Male | 26 | A 26-year-old man surgical resident at a tertiary care hospital in Lima, Peru with no relevant medical history, developed a cutaneous lesion one week after sustaining a needlestick injury in his third left hand finger while performing a cervical lymphadenopathy aspiration. Source patient had been admitted to the hospital with a known diagnosis of HIV infection, failing HAART and cervical lymphadenopathy. He received prompt HIV post-exposure prophylaxis with tenofovir/emtricitabine and raltegravir with negative baseline and follow up HIV test.
One week after accident swelling and erythema developed in the site of puncture (Fig. 1A). Lesion progressed to ulceration with sero-purulent discharge despite receiving oral and parenteral antimicrobials for 3 weeks. He was admitted for diagnostic work up and surgical management of wound. On examination: He was in good overall condition and vital signs within normal range, throughout the course of illness. A cutaneous skin ulcer was noted in his third finger of left hand with erythema of the ulcer margins and yellowish secretion (Fig. 1B) and limitation of affected finger mobility secondary to presence of the lesion. There were no enlarged regional lymph nodes and the rest of exam unremarkable. Blood-work including complete cell count, liver and renal function and chest and finger radiographs were normal.
A surgical exploration and debridement of the finger lesion was performed and tissue for biopsy and bacterial, fungi and mycobacterial cultures were sent. Histopathologic findings revealed an acute and chronic inflammation, with epithelioid granulomas, Langhan's giant cells and foci of caseous necrosis (Fig. 2A). Ziehl-Neelsen (ZN) stain detected the presence of acid-fast bacilli (Fig. 2B). Six weeks later, tissue culture grew one colony of Mycobacterium tuberculosis and Genotype MTBDR Plus showed isoniazid and rifampicin sensitivity.
The patient was treated with weight-adjusted doses of four-drug tuberculosis treatment (isoniazid, rifampin, pyrazinamide and ethambutol) for 2 months followed by 6 months of a two-drug regimen with gradual resolution of lesion (Fig. 1C) and full functional recovery.
Additional management included restriction to perform procedures and direct patient care until complete healing of ulcer. | cutaneous tuberculosis, healthcare worker, inoculation | Not supported with pagination yet | null |
PMC8415386_01 | Male | 18 | An 18-year-old male presented to a local emergency department following a high school football game. He complained of hoarseness and difficult, painful swallowing. During the game, he was running with the ball when he was hit in the facemask of his helmet twice during the same play. After the first hit, the chinstrap of his helmet became dislodged posteriorly and rotated under his chin. With the second hit to his facemask, he felt the chinstrap tighten, forcing him to swallow. He continued to play a majority of the game but began to notice anterior neck pain, shortness of breath, odynophagia, sore throat, and hoarseness.
On initial examination, the patient's voice was raspy and he complained of anterior neck pain with odynophagia. The decision was made to transfer the patient to the nearest Level I trauma center for further evaluation of suspected blunt neck trauma.
Upon arriving at the trauma center approximately one hour later, the physical exam revealed a small (1 cm) midline mandibular laceration, stable vital signs, and clear breath sounds bilaterally. Mild soft tissue swelling of the neck suggesting possible subcutaneous emphysema was found, however, no crepitus was noted. A chest radiograph was within normal limits. The patient's cervical spine was non-tender to palpation along the spinous processes with full range of motion.
Cervical radiographs revealed air in the prevertebral soft tissues, posterior to the hypopharynx (Figure 1). A computed tomography (CT) scan of the neck was performed, revealing an irregularity of the posterior hypopharyngeal wall and extensive air in the soft tissues of the neck extending from the nasopharynx to the mediastinum (Figures 2 and 3). An esophagram confirmed the diagnosis of a small posterior hypopharyngeal perforation (Figure 4).
The patient initially was admitted to the Intensive Care Unit for close observation. He was kept nil per os (NPO) and treated conservatively with cefotetan 1 gram every 12 hours and metronidazole 500 milligrams every 12 hours intravenously. Esophagrams were repeated every two days and showed gradual improvement with no extravasation noted by the sixth day of hospitalization. At that time, the patient was afebrile with a normal white blood cell count and differential. His initial symptoms of anterior neck pain, shortness of breath, and odynophagia were resolved. The patient was dismissed on a clear liquid diet with close outpatient follow-up. An esophagram three weeks after the initial injury confirmed a healed lesion. | blunt injuries, esophageal perforation, hypopharynx, neck injuries | Not supported with pagination yet | null |
PMC9977546_01 | Male | 58 | A 58-year-old male patient, known case of diabetes mellitus, presented to the outpatient department with complaints of edema in the hands, feet, and around the eyes for about one month and a decrease in the frequency of urination. The patient had no history of using herbal products, smoking, or alcohol. The abdomen was soft, and no defensive rebound was found in the physical examination. Edema was present in the pretibial, periorbital, and sacral regions. He had rales at the bases of both lungs on auscultation. There was no palpable lymphadenopathy. The patient's laboratory tests are summarized in Table 1. He was admitted to our ward with a prediagnosis of acute renal injury and nephrotic syndrome.
According to the detailed history taken after the patient was admitted to the ward, he received the 1st dose of the Pfizer-BioNTech COVID-19 vaccine about 50 days ago and began to develop edema after the vaccination. He had the 2nd dose of Pfizer-BioNTech COVID-19 vaccine a week ago. Therefore, he presented to the outpatient clinic due to the progressive increase in his complaints after 2nd dose of vaccination. The patient was hypertensive in the ward follow-ups. Ultrafiltration treatment was carried out 7 times intermittently to the patient who had an allergic course with resistant hypertension and diuretic-resistant hypervolemia. As the patient had hypoalbuminemia in the laboratory tests and diffuse edema in the whole body in the physical examination, a 24-hour urine collection was planned for the patient. Proteinuria of 15,935 milligrams/day was detected in 24-hour urine. Thus, the nephrotic syndrome was considered, and tests were performed to exclude rheumatological diseases in the etiology of nephrotic syndrome. In the examinations performed, c3 and c4 levels were normal. ANA, c-ANCA, p-ANCA, anti-Scl-70, anti-Jo-1, anti-SS-A, anti-SS-B, anti-dsDNA, and anti-GBM results were negative. In the hepatitis serology of the patient, HbsAg, anti-HAV IgM, anti-Hbc IgM, anti-HCV, and anti-HIV were negative. The COVID-PCR test, performed twice with a 48-hour interval, was negative. No drug could cause nephrotic syndrome among the drugs he used, and there was no drug that he had just started. There was bilateral pleural effusion in the chest X-ray. No erythrocyte casts were detected in the urine sediment from the patient.
On the other hand, leukocyte and hyaline casts were noticed in the patient's urine. As a result, tuberculosis PCR and AFB were planned for sterile pyuria, but these tests were negative. The patient was examined for microvascular complications to exclude nephrotic syndrome due to diabetes mellitus and retinopathy was not detected in the examination. Peripheral smear, immunofixation electrophoresis, and protein electrophoresis were implemented to exclude multiple myeloma and other plasma cell dyscrasias because of the high sedimentation level, anemia, and nephrotic level proteinuria (while spot urine protein was negative by the dipstick method, 16 g/day proteinuria was found in 24-hour urine). No atypical cell and roll formation was detected in the peripheral smear. IgM kappa monoclonal gammopathy was detected in immunofixation electrophoresis. Abdominal ultrasound demonstrated no pathology, and superficial ultrasound did not detect lymphadenopathy. Bone marrow biopsy was performed, and the biopsy reported a hypercellular bone marrow and aspiration smear with increased myeloid and erythroid series. Flow cytometry sent from the bone marrow sample was not compatible with myeloma. As a result of the examinations, multiple myeloma and other plasma cell dyscrasias were excluded from the case. Considering the current clinical situation of the patient and the fact that monoclonal gammopathy detected in the bone marrow may also be observed in renal lymphoma, positron emission tomography (PET-CT) was carried out on the patient. No malignancy or additional pathology was suggested after the PET-CT findings. Cryoglobulins were tested to exclude the causes of secondary nephrotic syndrome, and it was negative. Rectal biopsy was performed to exclude amyloidosis in the patient with diffuse edema at the nephrotic level and biopsy was negative for amyloidosis. Lower extremity Doppler ultrasonography was performed because of edema in both lower extremities, and deep vein thrombosis was not found in the ultrasonography. A renal biopsy was planned for the patient to determine the cause of the newly developed nephrotic syndrome. Renal biopsy demonstrated that findings were consistent with minimal change disease (Figures 1-3).
We started 80 mg of methylprednisolone intravenously. Afterward, urea and creatinine values decreased, and urine output returned to normal. The dose was gradually reduced, and the patient continued methylprednisolone treatment. The clinical picture of hypervolemia improved on the 10th day after the treatment. The proteinuria decreased to 67 milligrams in the 24-hour urine collected as control samples. The patient is followed up with 16 mg methylprednisolone treatment. The history taken from the patient showed that his symptoms developed after the Pfizer-BioNTech COVID-19 vaccine. Hence, secondary causes of nephrotic syndrome were excluded with the examinations. The case was evaluated as a minimal change disease developed after the Pfizer-BioNTech COVID-19 vaccine, since the complaints in the history and the current clinic developed after the vaccine. | null | Not supported with pagination yet | null |
PMC5798098_01 | Female | 20 | A 20-year-old female patient presented with fever for 2 months, associated with chills and rigors, evening raise of temperature and cough with expectoration. There was a history of vomitings for 10 days with the loss of appetite and weight loss. The patient did not respond to higher antibiotics for 7 days. Laboratory investigations revealed erythrocyte sedimentation rate (ESR) 100 mm/h, total leukocyte count was 5300 cells/cu mm, and C-reactive protein levels (CRP) >320 mg/L. Mantoux test and sputum for acid-fast bacillus (AFB) were negative. Antinuclear antibodies (ANA) were positive by indirect immunofluorescence test. Ultrasound abdomen revealed mild-to-moderate ascites and minimal left pleural effusion. Patient underwent 18F-FDG PET-CT for evaluation of fever of unknown origin.
On 18F-FDG PET-CT, maximum intensity projection (MIP) image revealed linearly increased tracer concentration in large vessels and multiple foci of increased FDG uptake in mediastinum and abdomen. Transaxial images showed increased FDG uptake in mediastinal lymph nodes, abdominal lymph nodes, wall of arch of aorta, thickened wall of ascending aorta, and pericardial effusion. Non-FDG avid left moderate pleural effusion and moderate ascites noted. Then, the patient was diagnosed to have disseminated extrapulmonary tuberculosis (TB) with aorto-arteritis. Treatment was started with antitubercular treatment (ATT) and low-dose steroids. Patient responded well and symptomatic improvement was seen after 3 months [Figure 1]. | 18f-fluorodeoxyglucose positron emission tomography-computed tomography, aorto-arteritis, extrapulmonary tuberculosis, inflammation, large vessel vasculitis | Not supported with pagination yet | null |
PMC5798098_03 | Female | 40 | A 40-year-old female patient presented with tightness of chest for 15 days, history of weight loss, decreased appetite, body pains, weakness, and no history of fever. Laboratory investigations revealed ESR 118 mm/h, CRP >24 mg/L, total leukocyte count 10,100 cells/cu mm. ANA, Rheumatoid factor (RF), anti-cyclic citrullinated peptide were negative. Patient underwent contrast-enhanced CT chest that revealed mediastinal lymphadenopathy, left minimal pleural effusion, pericardial effusion, and hypodense lesions in liver. There was a clinical suspicion of malignancy and the patient was referred for 18F-FDG PET-CT.
On 18F-FDG PET-CT, MIP image revealed foci of increased FDG uptake in mediastinum. Transaxial images showed increased FDG uptake involving enlarged mediastinal lymph nodes, thickened walls of ascending aorta and arch of aorta and pericardial thickening with effusion [Figure 3]. Non-FDG avid left pleural thickening was noted. PET-CT findings were suggestive of extrapulmonary TB with aortoarteritis. Patient was treated with ATT for 9 months. Follow-up 18F-FDG PET-CT was carried out after 6 months of treatment which showed complete metabolic and morphologic response [Figure 4]. | 18f-fluorodeoxyglucose positron emission tomography-computed tomography, aorto-arteritis, extrapulmonary tuberculosis, inflammation, large vessel vasculitis | Not supported with pagination yet | null |
PMC6551867_01 | Male | 75 | A 75 years old man, smoker, with a past history of a hepatic transplantation 13 years earlier for a hepatocellular carcinoma, was admitted to hospital with hemoptysis and dyspnea. He performed a chest CT scan, showing a solid lesion in the apical segment of right lower lobe with multiple confluent mediastinal adenopathies and right paratracheal lymphadenopathy (Fig. 1).
We practiced a videobronchoscopy that showed two small sessile lesions approximately 4.5 cm far from the carina on the right lateral wall of the trachea, which were removed with biopsy forceps. EBUS-TBNA was performed on the right paratracheal lymph node. The pathological findings were suggestive for hepatocarcinoma metastases and the patient was underwent chemotherapy.
After six months, the patient returned to the emergency room for wheezing and acute respiratory failure. Chest x-ray and CT scan showed deterioration of the radiological picture with stenosis of the tracheal lumen (Fig. 2).
The patient made videobronchoscopy that showed a vegetative neoformation which obstructed the tracheal lumen about 6.5 cm far from the true vocal cords (Fig. 3). The patient was intubated with a rigid bronchoscope Storz n 14 and we used laser photocoagulation to devascularize the lesion that was subsequently removed with a debulking maneuver, recanalizing the trachea (Fig. 4). The anatomopathological findings confirmed the previous diagnosis of hepatocarcinoma metastases (Fig. 5). | null | Chest enhanced computed tomography (CT) showed a solid lesion in the apical segment of right lower lobe with multiple confluent mediastinal adenopathies and right paratracheal lymphadenopathy. |
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PMC6551867_01 | Male | 75 | A 75 years old man, smoker, with a past history of a hepatic transplantation 13 years earlier for a hepatocellular carcinoma, was admitted to hospital with hemoptysis and dyspnea. He performed a chest CT scan, showing a solid lesion in the apical segment of right lower lobe with multiple confluent mediastinal adenopathies and right paratracheal lymphadenopathy (Fig. 1).
We practiced a videobronchoscopy that showed two small sessile lesions approximately 4.5 cm far from the carina on the right lateral wall of the trachea, which were removed with biopsy forceps. EBUS-TBNA was performed on the right paratracheal lymph node. The pathological findings were suggestive for hepatocarcinoma metastases and the patient was underwent chemotherapy.
After six months, the patient returned to the emergency room for wheezing and acute respiratory failure. Chest x-ray and CT scan showed deterioration of the radiological picture with stenosis of the tracheal lumen (Fig. 2).
The patient made videobronchoscopy that showed a vegetative neoformation which obstructed the tracheal lumen about 6.5 cm far from the true vocal cords (Fig. 3). The patient was intubated with a rigid bronchoscope Storz n 14 and we used laser photocoagulation to devascularize the lesion that was subsequently removed with a debulking maneuver, recanalizing the trachea (Fig. 4). The anatomopathological findings confirmed the previous diagnosis of hepatocarcinoma metastases (Fig. 5). | null | Chest radiography and Computed Tomography (CT) showed a solid neoplastic lesion in the apical segment of the right lower lobe and significant stenosis of the tracheal lumen. |
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PMC7768007_01 | Male | 37 | A 37-year-old Chinese man presented to our hospital in April 2020 with red, swollen eyes, acute worsening exophthalmos, and intermittent diplopia sustained for 7 days. A year earlier, he had been diagnosed with HIV-1 and had started ART [lamivudine (3TC) 300 mg daily, tenofovir disoproxil 300 mg daily, and dolutegravir 50 mg daily] regimen. Following the ocular symptoms, the tenofovir disoproxil and dolutegravir were replaced with lopinavir/ritonavir 400 mg/100 mg twice a day and zidovudine (ZDV) 300 mg twice a day at another hospital one week before this visit. His nadir CD4+ T cell count was 242 cells/mul, which increased to 717 cells/mul at the time of examination. His HIV RNA load was less than 20 copies/ml. He was afebrile. An ophthalmologic examination showed proptosis, congested, and edematous conjunctivae, protruding beyond the lid margin, without ptosis. His corneas, fundi, and visual acuity were normal ( Figure 1A ), though his eyeball mobility was limited bilaterally. The patient had no personal or family history of autoimmune disease.
Orbital computed tomography (CT) confirmed that both eyes were slightly protruding. The extraocular muscles, especially the superior and inferior recti, were enlarged bilaterally ( Figures 2A-C ). The optic nerves were normal. Ocular color ultrasound imaging showed mild, bilateral vitreous opacities and widening of the superior ophthalmic veins. Brain magnetic resonance imaging (MRI) showed no parenchymal abnormality. Contrast-enhanced MRI revealed thickening and increased signal intensity of the extraocular muscles, including the tendinous insertions. Both eyelids and lateral soft tissues showed diffuse swelling, without the lacrimal gland and periorbital fat involvement ( Figures 2D-F ). Aztreonam and clindamycin intravenous antibiotics were administered for 3 days; nonetheless, there was no clinical improvement.
Graves' orbitopathy (GO) was initially suspected. However, thyroid function tests involving measurements of triiodothyronine; thyroxine, thyroid stimulating hormone, thyroglobulin, thyroid peroxidase, and thyrotropin receptor antibodies as well as color-flow Doppler sonography scan, were normal. Further blood results included the following: serum immunoglobins [IgA, 4.03 g/L (range 0.7-3.8 g/L), IgG, 12.39 g/L (7-17g/L), IgM, 1.89 g/L (0.6-2.5 g/L)] and antibody tests (1:100-positive antinuclear antibody and negative antineutrophil cytoplasmic antibody). The orbital involvement in immunoglobulin G4-related disease (IgG4-RD) was excluded due to normal serum IgG4 levels, absence of eosinophilia (leukocyte 9.39 x109/L, eosinophilia 0.42 x109/L), and lack of lacrimal gland involvement. Serum antibody tests for herpes simplex virus, varicella-zoster virus, cytomegalovirus, toxoplasma, and syphilis were negative. Serum Epstein-Barr virus-DNA was absent, and the blood T-SPOT. TB assay to detect T cells primed to mycobacterium tuberculosis (TB) infection was negative. Finally, a diagnosis of IRIS-associated orbital myositis (IRIS-OM) was considered. Dexamethasone (5 mg) was administered intravenously for 5 days, followed by oral prednisone (30 mg) daily. The patient's proptosis, diplopia, and limited ocular movements improved considerably ( Figures 1B, C ) with an MRI of the extraocular muscles showing reduced swelling ( Figures 2G-I ).
Three months later, when tapering the prednisone, the patient presented with left ptosis, followed immediately by bilateral ptosis and diplopia ( Figures 1D, E ). He complained of facial muscles' weakness when chewing and weakness of both upper limbs' muscles while driving. Neurological examination showed bilateral ptosis and disconjugate eye movements without detectable facial or upper limb muscles' weakness. His sensation, coordination, and deep tendon reflexes were normal. A neostigmine challenge test was positive. Further blood tests showed a positive result for the ryanodine receptor (RyR). Acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and titin receptor antibodies were negative. Creatine kinase levels were within normal limits (105 U/L; normal range 39-308 U/L). A chest CT scan results excluded thymus abnormalities. Routine nerve conduction studies of the right facial nerve, left ulnar nerve, and left median nerve were normal. Low frequency and high frequency repetitive nerve stimulation using the standard approach was used to evaluate the left ulnar nerve and right facial nerve. The left ulnar nerve demonstrated normal responses, whereas the right facial nerve demonstrated 15% decrement in amplitude at low frequencies without enhancement at high frequencies. Single fiber electromyography (EMG) and needle EMG were not performed. Based on the outlined findings, the patient was diagnosed with probable IRIS-associated MG. He was treated with oral pyridostigmine bromide, 60 mg three times per day; tacrolimus, 1 mg twice a day; prednisone, 30 mg once a day for 2 weeks, followed by 20 mg daily for 3 months. One month later, the patient showed considerable improvement ( Figure 1F ); facial and upper limb muscle weakness improved more rapidly than the ptosis. At the time of this report, the serum creatine kinase was 33 U/L (39-308 U/L), the CD4+ T cell count had dropped to 369 cells/mul, and the HIV RNA load was undetectable. He had no complaints with the current pyridostigmine bromide (60 mg daily), prednisone (20 mg daily), and tacrolimus (2 mg daily) treatment regimen, together with ART ( Table 1 ). | acquired immune deficiency syndrome, antiretroviral therapy, autoimmune diseases, myasthenia gravis, orbital myositis | Not supported with pagination yet | null |
PMC4748193_01 | Female | 49 | A 49-year-old white woman presented with dysphagia for solid food since her early in her second decade. She had one food impaction requiring a hospital visit, and had symptoms suggestive of food impaction almost every week. She rarely reported heartburn. Her past medical history included celiac sprue treated with a strict glutenfree diet for the last 20 years. Ten years prior, endoscopy with bougie dilation was associated with severe chest pain for several days. An endoscopic biopsy 5 years prior showed >15 eosinophils in 2 HPF consistent with EoE.
Subsequently, she was treated with fluticasone (2 puffs BID) then budesonide (1 gm BID slurry); both were associated with side effects (headaches, sore throat, and thrush) resulting in termination after 2-3 weeks. She had taken PPIs in the past, including dexlansoprazole 30 mg for several months in the last year, but these medications did not help her symptoms. Repeat biopsy was not performed. Six months prior to her presentation she was placed on a 6-food elimination diet, to which she was adhering with the aid of a dietician. She avoids nuts and seafood due to an oral allergy syndrome, wheat, and now eggs, dairy products, and soy. Currently, this is her only active treatment for EoE.
On initial endoscopy, the 10-mm adult scope could not be passed due to esophageal narrowing 20 mm from the teeth; a 5 mm pediatric scope was used. The entire esophagus was pale and narrowed throughout, with no exudate, rare furrows, and incomplete rings in the mid-esophagus. At the Z line (37 cm) was a peptic-appearing ring with a 2-cm hiatal hernia. Four biopsies were obtained from the distal and 2 from the proximal esophagus. Savary dilation was performed from 9 mm to 12 mm with moderate resistance. Following the dilation, she had mild-moderate pain for 5 days, requiring narcotic analgesia.
Initial biopsies showed 400 eosinophils per HPF from both the proximal and distal esophagus, associated with lamina propria fibrosis, despite 6 months of the 6-food elimination diet (Figure 1). She was started on dexlansoprazole 60 mg AM. Three further endoscopies and dilation followed at monthly intervals (Figure 2). The final 2 dilations were performed with Maloney bougies.
After 2 months on PPI, there was a dramatic decrease in eosinophils, but still in the abnormal range (55 distal; 15 proximal; Figure 3). By 4 months, esophageal histology had normalized (5 distal; 2 proximal; Figure 4). The esophageal lumen was progressively dilated to 17 mm diameter; all signs of inflammation had resolved and the normal vascular pattern returned. The patient is currently eating more foods without difficulty or transient food impactions. She will remain on dexlansoprazole 60 mg AM, and the eliminated foods will be slowly re-introduced into her diet. | null | Not supported with pagination yet | null |
PMC7725127_01 | Male | 71 | A 71-year-old male with a past medical history of cervical spinal fusion surgery, C5 nerve palsy, lumbar spinal decompression surgery, and non-Hodgkin lymphoma status post chemotherapy with R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) presented to his primary care physician with concerns of chronic recurrent right hip and lower back pain which acutely worsened. The patient also acknowledged new-onset progressive numbness of his right thigh with associated intermittent, sharp muscle spasms. However, the patient denied recent urinary or bowel incontinence and speech or vision changes.
The patient's physical exam was unremarkable aside from poor coordination, hyperalgesia of the bilateral lower extremities, moderate tenderness to palpation of the lumbar spine at L1-L2 level, a positive bilateral straight leg test, and an unsteady tandem gait. Skin examination also revealed a violaceous plaque noted on the patient's anterior right thigh just above the knee. An initial lumbar magnetic resonance imaging (MRI) with contrast was completed and revealed moderate multilevel lumbar spondylotic changes with facet joint degeneration without evidence of destructive osseous lesions or intradural masses. Given these relatively benign physical exam and radiographic findings, the patient was diagnosed with lumbar radiculopathy and treated with analgesics and a fluoroscopy-guided lumbar transforaminal epidural (LTFE).
Despite initial treatment, the patient's pain progressively worsened, therefore, he was scheduled for a repeat lumbar MRI to elucidate the etiology of his pain and worsening motor weakness. Repeat lumbar MRI with and without contrast was completed two months after he initially became symptomatic. It showed an abnormal focal increased T2 signal and a rounded area of enhancement within the right posterior aspect of the distal thoracic cord at the T11 level. The etiology of this new lesion was unclear and a thoracic MRI with and without contrast was completed and showed a pathologic cord signal with expansion and abnormal enhancement involving T7-T12 (Figures 1 and 2). The differential diagnoses at this time included transverse myelitis, recurrent lymphoma, cord infarction, or neoplasm.
The patient was admitted to the hospital for further evaluation and management. Upon hospital admission, the patient was afebrile with normal vital signs. Initial lab work revealed a white blood count of 6.3 x 103/mm3, hemoglobin of 9.6 g/dL, platelets of 277 x 103/mm3, neutrophils at 53%, and lymphocytes at 33%. Inflammatory markers revealed an erythrocyte sedimentation rate of 104 mm/hr and c-reactive protein of 4.0 mg/L. The patient's HIV test was negative. Cerebrospinal fluid analysis was completed to rule out the possibility of lymphomatous meningitis. CSF analysis revealed a clear, colorless sample with lymphocytic pleocytosis and elevated protein. Atypical lymphocytes were noted, but no evidence of lymphoma was observed on flow cytometry. Microscopic testing of the cerebrospinal fluid for acid fast bacteria, fungi, mycobacterium, and cryptococcus neoformans were negative. The patient's TB spot test also was negative.
F-18 fluorodeoxyglucose (FDG) PET/CT imaging divulged a linear focus of mildly accentuated FDG activity from the middle of the T10 to the middle of the T11 vertebral body, correlating with the signal abnormality noted in prior imaging studies. Biopsy of the lesion was subsequently performed to establish a histopathological diagnosis. The biopsy disclosed an area of necrosis surrounded by pale histiocytes consistent with necrotizing granulomatous inflammation. Given the imaging and histopathological findings, the suspicion was that the lesion represented spinal tuberculosis. However, initial special stains of the biopsy specimen for microorganisms, including Ziehl-Neelsen and Grocott methenamine silver stains, were negative. Additional stains of the biopsy specimen for microorganisms, including the Fite stain for acid fast bacilli and periodic Acid-Schiff for fungi, were completed and revealed rare acid-fast bacilli identified on Fite stain, thus confirming the suspected diagnosis of intramedullary spinal tuberculoma.
The patient was initiated on an anti-tuberculous pharmacotherapy regimen of rifampin 600 mg/day, isoniazid 300 mg/day, pyrazinamide 1500 mg/day, and ethambutol 1200 mg/day (RIPE therapy), supplemented with adjuvant pyridoxine 50 mg/day. He was continued on RIPE treatment for two months followed by 10 months of continuation therapy with rifampin and isoniazid alone. Pharmacotherapy was supplemented with analgesics, physical therapy, and occupational therapy. The patient was followed on a monthly basis in the outpatient setting throughout treatment. After completing 12 months of pharmacotherapy, a repeat thoracic MRI with and without contrast was done, which revealed slight improvement in the T2 hyperintense signal within the thoracic spinal cord adjacent to the focal areas of enhancement at T8 - T9 and T10 - T11. These focal areas of enhancement did not appear to have changed significantly and no new areas of enhancement or abnormal signal were observed to suggest disease progression. Over the next two years he had persistent radicular pain, but his disability significantly improved from initial presentation. He is alive without recurrence of disease and has had significant improvement in his gait and mobility, now ambulating with a cane. | central nervous system tuberculosis, spinal cord, tuberculoma | Not supported with pagination yet | null |
PMC5379815_01 | Female | 22 | A 22-year-old, right-handed housewife presented to the hospital with complaints of headache of 15 days duration. Headache was generalized, intermittent in duration, aching in nature, associated with vomiting and visual obscurations, especially while changing positions. These symptoms aggravated in morning hours. There was also history of single episode of generalized tonic-clonic seizure 10 days back, after which the patient was started on anticonvulsants and there were no further episodes. Patient also noticed weakness of the right upper limb since last 8 days, which was gradual in onset and progressive in nature. Weakness was more significant in the left hand as compared to the left shoulder. There was also history of drowsiness since last 2 days.
On neurological examination, the patient was conscious, cooperative, and well oriented in time, place, and person with normal higher mental functions. Visual acuity was 6/9 in both eyes. Fundus was showing grade 1 papilledema on both sides. The rest of the cranial nerves' examination was normal. Nutrition and bulk was normal in all four limbs. Tone was increased on the right side. Power was 4+/5 in the right shoulder and 4/5 in the right elbow and right wrist. Grip was weaker on the right side as compared to the left side. Rest of the limbs had normal power. Sensory examination did not reveal any abnormality. Reflexes were brisk in the right upper limb, rest were normal. Gait was normal. Plain radiograph of the skull was normal.
Computed tomography (CT) scan [Figure 1] showed a lesion of 3.4 cm x 2.4 cm in size with well-defined margins and multiple foci of calcification in the left fronto-parietal region. The lesion was strongly enhancing inhomogenously on contrast administration with surrounding perifocal edema and mass effect suggestive of glioma or tuberculoma.
Magnetic resonance imaging (MRI) [Figure 2] scan was suggestive of a thick ring-enhancing lesion seen in the left high parietal region with perifocal edema with mass effect suggestive of granulomatous lesion, most likely tuberculosis.
CT angiography [Figure 3] showed a small lesion in the left high parietal region with increased vascularity.
Patient was operated with left parietal craniotomy with total excision of lesion. The tumor was adhered to the undersurface of dura. The tumor was dark brown in color, necrotic, and solid with increased vascularity. There were feeders from the periphery. The brain was edematous and pulsating well. Lax duraplasty was done using pericranium. Tumor was excised in toto.
Postoperatively, the patient recovered well. She was relieved of headache completely and there were no further episodes of vomiting or seizures. The right upper limb weakness improved to 4+/5. The blurring of vision also improved gradually. There was no new neurological deficit postoperatively.
Postoperative CT scan [Figure 4] showed complete excision of the lesion.
The patient was discharged on 10th postoperative day without any neurological deficit.
Neuropathological [Figure 5] examination showed a tumor composed of peripherally arranged tumor cell in sheets and syncytium. These were large cells having moderate eosinophilic to clear cytoplasm with dense hyperchromatic nuclei and increased nucleocytoplasmic ratio and prominent macronucleoli. The tumor showed mitotic activity of about 1-2/high power field, and extensive areas of necrosis and hemorrhage suggestive of primary choriocarcinoma of the left parietal lobe.
In view of the diagnosis of choriocarcinoma, the patient was investigated extensively for the detection of the primary lesion. b-Human chorionic gonadotropin (b-HCG) was 20,000 IU. Gynecology opinion was taken Patient was pregnant once and had delivered full-term baby vaginally 2 years back without complications. Past and present menstrual history was normal. Transvaginal ultrasound was normal. X-ray chest was normal. CT scan abdomen and pelvis did not reveal any abnormality.
The patient has been referred to another specialized institute for adjunctive treatment. She has been following up regularly with evidence of widespread metastasis over a period of 6 months. | choriocarcinoma, enhancing, intracranial, primary, ring | Not supported with pagination yet | null |
PMC3546444_01 | Male | 37 | A 37-year-old male patient was admitted with a history of perianal discharge and ulceration for the last four months. According to his medical history, he was treated for a perianal abscess which was incised and drained one year ago, yet, despite the initial healing, it recurred two months later.
During the clinical examination at the admission, the patient, with a weight of 40 kg was relatively dehydrated and had tachycardia (pulse rate, 110/min). Physical examination revealed body temperature 38,5 C, and arterial pressure of 09/06 mmhg. No lymphadenopathy was found on palpation; in addition abdominal examination revealed a generalized tenderness.
The perianal region examination showed large bilateral infected ulcerations followed by pus (Figure 1). The digital rectal one revealed no pathological findings except a slight sphincter hypotonia. Anoscopy was normal and no fistulas were noted. The rectosigmoidoscopy showed no abnormalities as well.
Laboratory investigations showed a hemoglobin level of 09.3 g/dL, a raised white blood cell count of 12,300/muL in addition to high C-reactive protein and elevated erythrocyte sedimentation rate of 50 mm/h. The other laboratory data were within normal limits.
The abdominal X-ray revealed bilateral nonhomogenous infiltrations and cavitary lesions in the right lung (Figure 2). A contrast-enhanced computed tomography scan of the abdominal and pelvic region showed multiple mesenteric and retroperitoneal necrotic adenopathies (Figure 3). The patient was taken to the operating room where a diagnostic laparoscopy was performed and thus showed a thickened and hyperemic peritoneum with Multiple and yellowish white granulations diffusely distributed on the parietal peritoneum and the omentum. Multiple mesenteric adenopathies were noted too. Multiple biopsies of the peritoneum granulations and a diverting sigmoidostomy were performed.
The perianal lesion was cured and biopsy material was taken. Histological examination of all biopsies showed epithelioid granulomas and Langhans' type multinucleated giant cells, with the presence of caseous necrosis (Figure 4). Culture swabs from the perianal lesion confirmed mycobacterium tuberculosis. Examination of sputum samples for tuberculosis was performed but no Mycobacterium tuberculosis was found. A tuberculosis skin (PPD test) revealed a positive reaction with 22 mm of induration. The human immunodeficiency virus antibody test was negative.
We made a diagnosis of perianal tuberculosis with pulmonary and peritoneal involvement and started antituberculous treatment that is consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol for the first two months. No side effects occurred. The patient symptoms vanished and the perianal ulcer began to heal within the first month of treatment. Therapy with isoniazid and rifampicin took seven months. After six months of treatment, the lesion had disappeared, and only a bilateral mild granular region remained (Figure 5). Closure of the protective sigmoidostomy was performed. Now the patient is healthy and having no symptoms. Luckily, there is still no recurrence after one year of followup. | null | Not supported with pagination yet | null |
PMC5043393_01 | Male | 43 | A 43-year-old man, with no history of smoking, tuberculosis, respiratory diseases or trauma presented with a persistent non-productive cough with mainly postprandial onset with duration of approximately two years. The cough was particularly irrepressible after the intake of fluids. This had resulted in significant weight loss due to reduced food intake. Blood tests at presentation were normal. Computed Tomography (CT) of the thorax showed a hypodense lesion in the right pulmonary lower lobe. Water-soluble contrast radiography of the esophagus showed a broncho-esophageal fistula between the apical segmental bronchus of the lower right lobe and the middle section of the esophagus (Fig. 1a). Bronchoscopy showed a fistula opening that was 4 mm in diameter and approximately 2.5 cm distal to the main carina subsequently confirmed by CT scan 3D rendering (Fig. 1b). Esophagogastroduodenoscopy confirmed a fistula tract ending in the esophageal tract at 30 cm from the incisors. The patient underwent VATS under general anesthesia with selective ventilation and low levels of insufflation pressure in the right lung. The fistula tract was stapled at both ends using an Endo GIA device and excided. The chest tube (24 F placed through lower trocar incision) was removed on the first postoperative day. At the same time, a new esophagography was performed to show any esophageal leakage (Fig. 2). The patient resumed solid food 24 h after the operation. No post-operative complications were observed and there was complete remission of the presenting symptoms. He was discharged in good health on the third postoperative day. Two years after follow-up, there are no apparent complications. | adult, broncho-esophageal fistula, case report, video-assisted thoracic surgery | Not supported with pagination yet | null |
PMC7391021_01 | Male | 24 | It is obvious that people's movements are the cause of the COVID-19 outbreak. In this model, the movements of human agents were considered in two modes. They move either by their personal vehicles or public transportations. In this model, humans based on age were classified into four groups (Table 2 ): 5 and less, more than 5 to 24, more than 24 to 64, and more than 64. It was assumed that humans who are more than 24 years old (two last groups) can have personal vehicles, of which 63% were assumed to have personal vehicles according to the statistics of people having personal vehicles in Urmia city. It should be noted that the rest of humans were assumed to move by public transportations. On the other hand, humans based on the occupation were classified into four classes of civil servants, self-employed, students, and the rest of the people who are not in any of the first three classes. In this ABM, it was assumed that students were assigned to human agents who are more than 5 and less than 24 years old, and civil servants, as well as self-employed employees, were assigned to human agents who are more than 24 years old. Similarly, the number of human agents in each group was determined according to the statistics of human resources in Urmia city.
The selection of agents' workplaces was performed randomly among the office, business, or school cells on the basis of agents' occupations. During the simulation, for each human agent, a cell was assigned as the workplace and does not change. It should be noted that the same cell can be several human agents' workplaces since the selection of the workplaces was done randomly. In this model, all employees (civil servants and self-employed) and students move between their houses and workplaces twice a day. To simulate the movements of human agents, one day was divided into four time intervals: in the first time interval, employee agents (civil servants and self-employed) who have personal vehicles move from their houses to their workplaces by their own vehicles and in this time interval, there is not any risk of becoming infected for these human agents. On contrary, employee agents who do not have personal vehicles as well as student agents in order to move from their houses to their workplaces, use public transportations and in this case, they are likely to become exposed if there is any exposed human agent on their way to work regarding the R0 value of the exposed human agent as well as the COVID-19 transmission probability. It should be noted that the speed of public transportations with regard to their stops in stations was considered 45 km an hour and according to this speed, it was assumed that human agents move about 11.25 km every 15 min; therefore, the movements of human agents are updated every 15 min and their health status (see section 2.3.3) are investigated every 15 min based on the existence of exposed human agents in the same cells with them. It should be noted that in order to transmit the COVID-19 indoors, people should be kept at a distance of fewer than 2 m for at least 15 min; therefore, in this ABM, the time interval was considered 15 min and the dimension of the cells was taken into account 2 m. Human agents move between their houses and workplaces through road cells. All employees as well as students move to their own workplace cells in the second time interval and similarly, the probability of becoming exposed is investigated at their workplace cells. In the next time interval (the third time interval), employees and students come back from their workplaces to their houses in the same way described in the first time interval and the risk of disease transmission is investigated for employees who use public transportations as well as students; and in the last time interval, all employees and students move to their houses and in this time interval, the disease transmission is investigated among all members of the households. These processes are explicitly illustrated in Fig. 4 .
In our model, human agents at any moment of the simulation are in one of the susceptible, exposed, infected, recovered, or dead states and their states change regarding the SEIRD model. The states of human agents change under certain conditions over time. They will remain susceptible until they coincide with at least one exposed human agent in the same cells. In this case, based on the transmission probability as well as the R0 value of the exposed human agent, COVID-19 might be transmitted from an exposed human to a susceptible human. If the human agent becomes exposed, it starts to transmit the disease and this trend lasts 2-14 days (COVID-19 incubation period). After passing the incubation period which is considered diverse for each human agent, the state of exposed human turns into infected, and in this case, it will be quarantined. In the infected state, human agents cannot move and consequently spread the disease because of the quarantine. In the state of infected, one of two events regarding the age of the human agent happens: first, the infected human agent becomes recovered after 2-4 weeks, or second, the infected human agent dies. In Fig. 5 , the transition of states for human agents was shown.
In order to have an overview of the parameters of our ABM, input parameters of the model along with their values as well as the values assigned to the attributes of human agents were summarized in Table 3 . To initialize these values, previous studies and some of the most authoritative websites were used. For the parameters and attributes whose values were defined in a range, a normal distribution was considered. Moreover, for these parameters and attributes, the mean and standard deviation were also reported. It should be noted that the normal distribution was simply considered for these parameters and attributes due to the novelty of coronavirus as well as the lack of information on what distribution it follows (as a suggestion for future research, an investigation can be made on how these parameters (parameters defined in a range) are distributed; then, the values adjusted for these parameters would be based on the study of their changes in reality.).
In this research, all happened events concerned with the COVID-19 outbreak in the Urmia city along with their exact dates were considered in our ABM. In Iran, COVID-19 disease was transmitted from China to the city of Qom (the first city in Iran where COVID-19 was observed) and subsequently, from Qom to all cities in Iran. The first case of COVID-19 in the city of Urmia was identified on February 27. According to the official government news, this person had traveled to Qom and returned to Urmia on February 25; therefore, the beginning of our ABM was scheduled for February 25. In addition, one human agent was randomly considered exposed at the beginning of the ABM. Precede the outbreak of COVID-19 from Qom to all cities in Iran, the Iranian government in order to reduce the rate of COVID-19 outbreak closed all schools and educational centers on February 21. For this reason, at the beginning of our ABM, it was assumed that all student agents do not move in the ABM as well as about 30% of civil servant agents (those who are teachers in the real world). Similar to the first detected case, the second infected case with COVID-19 disease in the Urmia city was identified on March 2. This person also became infected due to traveling to Qom city and returned to Urmia city on February 28; so, another susceptible human agent was randomly selected among all human agents, and its health status was changed to exposed. In Iran, the New Year's holidays begin on March 18 and continue until March 23. During this period of time in the model, it is assumed that all human agents stayed at their houses and did not move to their workplaces or any other places. On March 27, the Iranian government in order to reduce the outbreak of the COVID-19 imposed the social distancing plan on the population. Regarding this event, only human agents who did not pay attention to social distancing were likely to become exposed. The interval between March 31 and April 1 was the official holidays of the New Year and similarly, all human agents were assumed to stay at their houses and there were not any human agents' movements in this interval in the model. It should be noted that in Iran, one day a week is a holiday and these holidays were also considered in the ABM according to the exact dates of them. Similar to other holidays, on these holidays, it was assumed that human agents stay in their houses and do not move. Fig. 6 clearly illustrates all that happened in the study area from the beginning of the epidemic to May 10 (the end of the simulation). | agent-based modeling (abm), control strategies, geospatial information science (gis), seird model, school closures, social distancing | Not supported with pagination yet | null |
PMC7472827_01 | Unknown | 2 | In July 2019, six 2-year old elk (Cervus elaphus) hinds were noted to be dull and depressed. The six animals were part of a herd of 17 animals (16 hinds and 1 bull), located on the National Animal Disease Center (NADC) campus in Ames, Iowa. Collectively, the herd was also noted to be anorexic for a few days prior to the identification of clinical signs. Closer examination revealed the six depressed hinds to be in poor body condition and had failed to completely shed their winter coats.
A second herd, consisting of 17 animals (16 hinds and 1 bull), housed in an adjacent pasture was also evaluated. Only one hind (#84) in this group was found to be in poor body condition. Blood samples from clinical animals were obtained for complete blood counts, serum chemistries, and infectious diagnostic testing. Fecal samples were also collected.
Complete blood counts (CBC) were unremarkable for all animals tested. However, serum chemistries (Table 1) showed a marked hypoalbuminemia. In two of the animals (#100 and #113), serum albumin levels were below the instrument's level of detection (i.e., < 1 mg/ml). Fecal floatation examinations were performed on individual animals, as well as from pooled fecal samples. Findings revealed occasional strongyle-type eggs (1-10 per slide) and occasional operculated eggs consistent with a trematode spp.
Blood and serum samples from all affected animals were submitted to the National Veterinary Service Laboratories (Ames, IA) for bluetongue virus (BTV), epizootic hemorrhagic disease virus (EHDV), malignant catarrhal fever (MCF), and bovine leukemia virus (BLV) testing. Three of the clinical animals were seropositive for EHDV, but no virus was recovered via PCR from any of the tissues submitted, suggesting exposure to EHDV, but no ongoing infection. All other test results were negative. Fecal samples were negative for Johne's (Mycobacterium avium subsp. paratuberculosis) via culture and polymerase chain reaction (PCR) for the IS900 genetic element.
At necropsy, all four elk were thin, with rough hair coats (Figure 1A) and decreased subcutaneous and renal fat stores. One of three hinds had fecal staining of the perineum consistent with diarrhea, while the remaining hinds had normal formed feces.
Abomasa from three of the four hinds were characterized by variable degrees of irregular abomasal mucosal thickening, which was most prominent in the fundus, but also extended well into the body. In one animal, the abomasal mucosa was cobblestone in appearance, with numerous raised, pale, nodular foci, 5-10 mm in diameter (Figure 1B), that coalesced in severely affected areas. In all four animals, the mucosal surface was covered with moderate to large amounts of mucus, while scattered throughout the thickened abomasal mucosa were small 1-3 mm red foci. At all levels of the small intestine, the mucosa was diffusely hyperemic. The cecum was less affected, with small multiple hyperemic foci. More distal regions of the large intestine were normal in appearance.
Sections of abomasum from all four hinds were characterized by variable degrees of hyperplasia and metaplasia. Elongated gastric pits were lined by tightly packed mucous cells with increased mitotic figures (mucous cell hyperplasia) resulting in moderate thickening of the abomasal mucosal layer (Figure 2A). Multifocally, mucous cells replace gastric parietal cells (mucous cell metaplasia). Within the lamina propria were moderately increased numbers of lymphocytes, plasma cells, and eosinophils (Figure 2B). Occasional dense aggregates of lymphocytes (lymphoid nodules) were seen in the abomasal lamina propria. Within the abomasal lumen multiple cross sections of a nematode, roughly 100 mum in diameter, were present (Figure 2C). Morphologic features were typical of Trichostrongyles, including a thin cuticle with prominent longitudinal ridges, pseudocoelom, and a platymyarian-meromyarian musculature (Figure 2C). The digestive tract was typical oligocytous strongylin with few visible cells and multiple nuclei.
Based on our initial clinical findings of poor body condition, diarrhea, and severe hypoalbuminemia, with no clinical pathologic evidence of hepatic or renal involvement, we proposed a tentative diagnosis of protein-losing enteropathy. Gross and histological findings of proliferative abomasitis and identification of nematodes consistent with Ostertagia spp. provided a definitive diagnosis of protein-losing enteropathy due to ostertagiasis. Furthermore, identification of increased number of lymphocytes, eosinophils, and plasma cells in the abomasum, confirmed type II ostertagiasis.
Anti-helminthic treatment was started immediately and consisted of a combination of transdermal Cydectin (5 mg moxidectin/ml, 5 ml/kg; Bayer Healthcare, Shawnee Mission, KS) and injectable Noromectin Plus (1% ivermectin and 10% clorsulon; 2 ml/45 kg; Norbrook Inc, Overland Park, KS). Clinical animals also received vitamin B complex (1 ml/45 kg; Huvepharma, Inc., St. Joseph, MO), administered subcutaneously. Five weeks after presentation of clinical signs, all elk were reevaluated. Previously-clinical animals remained thin, but their body condition had started to improve. Blood samples were collected and serum chemistries reanalyzed 5 weeks following treatment. In three of the four animals, albumin levels had started to improve (Table 2). Ten weeks after initial treatment, all animals were re-treated with injectable Noromectin Plus, and serum chemistries were again evaluated in previously-clinical animals (Table 2). At this sampling timepoint, serum albumin levels were within normal range for all animals analyzed. | ostertagia, case report, elk, fading elk syndrome, ostertagiasis | Not supported with pagination yet | null |
PMC3585710_01 | Female | 55 | The woman, 55 years old, is a housewife and a former smoker of 1 pack/years. She underwent a hysterectomy for uterine fibromatosis, and a surgical operation for right humerus osteochondroma. She has got a herpes simplex virus type I infection. At the time of our first observation she referred in the last 2 years dry cough with little sputum, dyspnea grade II according to the American Thoracic Society (ATS) scale and mild fever. At the beginning of the symptoms she performed a chest x-ray which showed "interstitial thickening" and a microbiological sputum examination which was negative for tuberculosis and fungal infection. The general practitioner gave her a non-specific antibiotic therapy with low benefit and then a steroid therapy with improvement in symptoms. At the time of our observation, she underwent a total-body CT scan which showed "a series of lung nodules distributed in all lobes; a solid slab in the mantle of the apical segment of the left lower lobe; several small adenomegalies in the anterior mediastinum, around the trachea and below aorta artery; no evidence of effusion in the pleural cavity" in the thorax (Figure 1). The CT scan showed the "presence of enlarged lymph nodes in the following areas: celiac/pancreatic lombo-aortical, bilateral internal iliac, bilateral obturator, bilateral external iliac and bilateral inguinal" in the abdomen.
The 6-min walking test was normal and the pulmonary function tests showed a reduction in the diffusing capacity for carbon monoxide (DLCO) (Table 1). The arterial blood gas analysis performed during spontaneous breathing at FiO2 of 0.21 showed mild hypoxemia at rest with minimal alterations of intrapulmonary gas exchange, and normal acid-base balance: PaO2: 73 mmHg; PaCO2: 37,9 mmHg; pH: 7,41. The serum level of angiotensin I-converting enzyme (ACE) was normal. | null | Not supported with pagination yet | null |
PMC3585710_02 | Male | 57 | The man, 57 years old, truck driver, is a former smoker of 54 pack/years. He has arterial hypertension, type 2 diabetes mellitus, chronic renal failure with mild anemia and an obstructive sleep apnea syndrome (OSAS) in severe obesity. As his wife, he has got a herpes simplex virus type I infection. He takes regular therapy with aspirin, doxazosin, allopurinol, irbesartan, erythropoietin and insulin. He referred dyspnea ATS grade II-III in the absence of cough. He also reported to have taken steroids in the past at the starting dose of 50 mg/day and gradually tapered. This therapy was recommended in the absence of a definitive diagnosis and on the basis of symptoms and radiological abnormalities of "interstitial thickening" present in the chest x-ray. At the time of our first observation, the pulmonary function tests revealed a mild restrictive pattern with reduction of DLCO (Table 2). The 6-min walking test showed that the distance walked during sub-maximal exercise was below the lower normal limit. The high-resolution chest CT scan showed "areas of increased ground-glass density in the right lower lobe, with parenchymal micro-nodules in the following lobes: left upper, lingula, left lower, middle, and right lower; multiple enlarged lymph nodes are present in the mediastinum, at the following areas: retrotracheal, paratracheal, aortopulmonary window, subcarinal and bilateral hilar; other enlarged lymph nodes are present at the origin of neck vessels, in the supraclavicular zone, and (in scans passing through the upper abdomen) bilaterally along the celiac tripod, peripancreatic area, along the gastro-lienal and epatogastric ligament". Both patients underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). The BAL fluid revealed a mild lymphocytic alveolitis both in the man (L = 22%) and in the woman (L = 18%) with a CD4/CD8 ratio of 3.1 in the former and 2.8 in the latter. The microbiological analysis of the BAL fluid was negative for common bacterial, tubercular and fungal infections. The TBB was non-diagnosticboth in man and in woman due to a poor and non-representative lung sample. For these reasons both patients underwent lymph node biopsy by mediastinoscopy which showed a "granulomatous epithelioid giant cell non-necrotising chronic lymphadenitis". | null | Not supported with pagination yet | null |
PMC9855748_01 | Male | 68 | A 68-year-old male was discovered to have a pulmonary nodule in a CT scan for 4 years with no apparent symptoms. The latest CT scan (10/2021) indicated a blade-like hyperdense shadow (2.4 cm x 2.0 cm) in the lower-left lung (Figure 1), which had a higher density than before (06/2019). The positron emission tomography/CT (PET/CT) showed that the standard uptake value (SUV) max of the nodule was 8.1 and had high suggestive of malignancy. Both CT and PET/CT reported that the nodule was located in the left dorsal segment (S6) (Figure 1). Considering the possibility of high suggestive malignancy, it was planned for this patient to receive a video-assisted thoracic surgery (VATS) lobectomy of the left lower lobe.
During intraoperative exploration, the patient was found to have a complete fissure splitting the upper lobe into two lobes (Figure 2). The accessory fissure completely splits the apicoposterior segment (S1 + 2) from the upper lobe. Therefore, there were three lobes in the left lung, including the S1 + 2 as an accessory lobe, the rest of the upper lobe, and the lower lobe. In addition, the target nodule was actually in the S1 + 2, not the S6 considered before surgery.
The surgery was changed to a segmentectomy of the S1 + 2. After the surgery, the patient recovered well and was discharged from the hospital after three days. The pathology of the lung nodule was granulomatous inflammation with caseous necrosis, with the positive antacid stain. The patient was eventually diagnosed with tuberculosis.
This misdiagnosis of location could be avoided, as the additional fissure, the real bronchus, and vessels of S1 + 2 and S6 were not tricky to identify in preoperative CT (Figure 3). Figure 4 shows a three-dimensional (3D) reconstruction of the lungs. The nodule was located in the S + 2, adjacent to the S6. A1 + 2a and A1 + 2b come from the posterior ascending artery, while A1 + 2c comes from the first trunk of the pulmonary artery. | ct scan, anatomy, chest, computed tomography, diagnosis, lung cancer, lung cancer surgery | Not supported with pagination yet | null |
PMC4151577_01 | Female | 65 | A previously healthy 65-year-old female patient was admitted in the medical unit of our hospital with a history of fever and persistent cough 1 month ago. General examination was unremarkable except for the presence of pallor. Respiratory system examination revealed bronchial breath sounds and crackles in the right infraclavicular area. Examination of other systems was normal. A panel of laboratory tests was performed which confirmed iron deficiency anemia.
Chest radiogram showed right upper zone homogenous opacity. The patient was diagnosed to have community acquired pneumonia and was treated with broad spectrum antibiotics. She was referred to pulmonary medicine in the second week of admission to rule out post-obstructive pneumonia, as there was no clinical response to the above mentioned treatment. A computed tomography (CT) of the thorax was performed; it revealed dense peripheral consolidation of the right upper lobe with enlarged pre- and paratracheal lymph nodes (Figures 1(a) and 1(b)). As the lesion was deemed not amenable for CT guided biopsy, bronchoscopy was done; it showed mucoid, tenacious, and thick cheese-like pseudomembrane completely lining the right upper lobe bronchial subsegments with a narrow but patent bronchial lumen (Figure 1(c)). All other bronchial segments were normal. Bronchial washing from the right upper lobe bronchus was positive (+++) for acid fast bacilli (AFB). Biopsy of the pseudomembrane-like lining was attempted; satisfactory samples could be obtained as the latter was very tenacious. A diagnosis of endobronchial and parenchymal TB was made and antitubercular therapy was instituted. | null | Not supported with pagination yet | null |
PMC4151577_02 | Female | 26 | A 26-year-old female was referred to us for evaluation of severe left sided chest pain of 1-month duration. A review of her records revealed that she had received directly observed therapy (WHO Category 1) for sputum positive pulmonary TB and had been declared cured 6 months prior to presentation. On examination, general physical examination was normal. Respiratory system examination revealed volume loss and absent breath sounds over left hemithorax suggestive of left lung collapse/fibrothorax. Sputum for AFB was negative.
Chest radiogram showed complete collapse of left lung with ipsilateral mediastinal shift (Figure 2(a)). CT of the thorax confirmed the chest radiographic findings (Figures 2(b) and 2(c)). A review of the patient's pretreatment chest X ray showed presence of left sided miliary shadows but no evidence of lung collapse (Figure 2(d)).
In view of lung collapse occurring after successful treatment of TB, bronchoscopy was undertaken to rule out endobronchial obstruction. Bronchoscopy showed complete occlusion of left main bronchus with only a pinhole sized opening (Figures 2(e) and 2(f)). Bronchoalveolar lavage was negative for AFB on staining and on culture. Endobronchial biopsy showed chronic inflammation with no granulomas. As the left main bronchus was completely cicatrized, the patient was unsuitable for stenting. A diagnosis of left main bronchostenosis secondary to tuberculosis was made and the patient was referred to the cardiothoracic surgeon for bronchial reconstruction/bronchoplasty. However, the patient declined to undergo any surgical procedure. | null | Not supported with pagination yet | null |
PMC2531199_01 | Female | 34 | The patient was a 34-year old, asymptomatic Zimbabwe-born woman with a positive HIV IgG ELISA on immigration screening in 2002. There was no prior history of sexually transmitted infections, genital or perianal ulceration, and syphilis serology was negative. Her absolute CD4+ T cell count at diagnosis was 156/mm3, with an HIV-1 RNA plasma viral load of more than 100 000 copies/mL. Antiretroviral therapy was initiated one month later, in October 2002, with combivir one tablet twice daily and nevirapine 200 mg twice daily, together with trimethoprim/sulfamethoxazole as primary prophylaxis against P. jiroveci pneumonia. By January 2003, her CD4+ T cell count had increased to almost 500/mm3, and her HIV viral load remained persistently undetectable after March 2003, at which point trimethoprim/sulfamethoxazole was discontinued. In April 2003, she noted multiple painful papules on the left labia, with subsequent superficial ulceration. She had no reported sexual contacts for over a year. Her family physician prescribed empiric therapy with acyclovir 400 mg three times daily and keflex 500 mg three times daily, followed by oral valacyclovir 500 mg twice daily.
In July 2003, nine months after starting HAART, the shallow ulcerations had resolved but a pruritic 1 x 3 cm granulomatous lesion developed on the left labia. This was associated with surrounding tissue edema, and shotty left inguinal lymphadenopathy, and progressed over the subsequent two months (Figure 1(a)). There was no response to azithromycin 1 gram weekly for 4 weeks, as empiric therapy for granuloma inguinale. Both a superficial swab and a punch biopsy of the hypertrophic lesion demonstrated HSV-2, with glassy nuclear chromatin, multinucleation and surrounding severe acute and chronic inflammation (Figure 1(b)). Topical therapy was initiated with trifluridine, together with oral valacyclovir 1 gram twice daily. There was no clinical response, although valacyclovir discontinuation was followed by an outbreak of painful, scattered shallow ulcerations that were culture positive for HSV-2. From November 2003 and December 2005 she was treated with 4 one-month courses of intravenous foscarnet; despite a near total clinical response to the first course, the response waned progressively and the fourth course was complicated by Staphylococcus aureus cellulitis at the line site. Lesion cultures were repeatedly positive for HSV-2, and a repeat labial biopsy in February 2006 showed only chronic granulation tissue. There was no response to a trial of topical protopic (tacrolimus) in August 2006.
In September 2006 there was a prompt clinical response to topical imiquimod 5%, applied 3 times weekly, with resolution of the lesion within eight weeks. She remains asymptomatic on oral valacyclovir 1 gram twice daily combined with topical imiquimod 5% as needed (approximately one topical application every two weeks) with minor residual labial scarring. | null | Not supported with pagination yet | null |
PMC9722297_01 | Female | 60 | A 60-year-old female patient was referred to the Department of Periodontology with the chief complaint of mobility of the maxillary anterior teeth. The patient was diagnosed with generalized severe chronic periodontitis and gingival recession due to bone loss in the central and lateral incisors, as well as canines. In addition, lateral incisors were rotated in place and were in an overlapped position on the central incisors, which caused crowding in the anterior maxillary segment. The same problem was previously addressed in her mandibular incisor with implant-supported FPD, but the periodontal prognosis was not acceptable, and the patient was unsatisfied with the esthetic and functional results.
Supra-gingival scaling and sub-gingival scaling were performed using Ultrasonic Piezo Scaler (DTE, Wuhan, China) and Gracey curette (Hu-Friedy Mfg. Co., LLC, Chicago, IL, USA), respectively. The periodontal indices were measured using a color-coded Michigan Williams probe (Premium Instruments, Ronkonkoma, NY, USA) after 4 weeks. They include gingival recession, pocket depth, and tooth mobility, as are shown and defined in Table 1. As the maxillary right and lateral incisors had grade II and III mobility with probing depths of 7 and 8 mm and more than 50% bone loss, respectively, with a hopeless periodontal prognosis, their extraction was recommended (Figures 1(a) and 1(b)). All the possible treatment modalities for the replacement of the lateral incisors and their costs, benefits, and prognosis were explained to the patient. After obtaining informed written consent, we chose and initiated the treatment plan with FRC bridge using natural tooth pontics.
The maxillary right and left lateral incisors were extracted under local anesthesia (1 cartridge of xylopen 2%; lidocaine 12 mg/epinephrine 12.5 mug/ml, Exir, Borujerd, Iran), and the extraction was performed atraumatically with no need of suture. The extracted teeth were scaled and polished thoroughly to remove all the deposits on them and kept in distilled water at the temperature of 4 C until the restorative procedure (Figure 2(a)).
After three weeks, the healing of the extraction socket was re-evaluated, and the stable periodontal status was affirmed (Figures 1(c) and 1(d)). An impression of the maxillary arch with c-silicon material (Speedex, Coltene, Langenau, Germany) and the study model was made in order to adjust the length and proximal contours of pontics and correct the crowding in the anterior maxillary segment. The approximate cutting location on the root of the lateral incisors was marked while holding the teeth near their previous location on the study model. The root section was initiated using a cylindrical diamond bur in a way that the remained tooth portion consisted of an anatomical crown, in addition to a part of the root due to mimicking the gingival recession (Figure 2(b)). The pontics seem shorter than the natural teeth due to the root section. However, the remained tooth structure represents the clinical crown of pontics in harmony with the appearance of adjacent teeth.
The opening of the root canal was enlarged in the tissue side of the pontics with round diamond bur (Jota, Ruthi, Switzerland; Figure 2(c)). The root canal space was instrumented (K-file, Dentsply-Maillefer, Tulsa, OK, USA) and then debrided with sodium hypochlorite (NaOCl) 2.5% (Sigma-Aldrich, St. Louis, MO, USA) and remained in place for 10 minutes followed by irrigation with normal saline (Figure 2(d)). The pontics were kept in distilled water at 4 C for one week in order to prevent the detrimental effect of NaOCl on the bond strength.
Then, the root canal space was washed with distilled water, dried using paper points, and filled with Vertise Flow as a Self-Adhering Flowable Composite (Kerr Dental, Kloten, Switzerland); it was cured (BlueLEX, GT 1200, New Taipei City, Taiwan) at the light intensity of 1200 mW/cm2 and wavelength of 470 nm for 40 seconds from each aspect of the pontics (Figure 2(e)). Then, the proximal contours of the pontics were stripped using cylindrical diamond bur (Jota) in order to achieve the appropriate intra-arch position and correct the crowding in the anterior maxillary segment. There was no need for occlusal plan correction before the placement of RBB due to the corrected alignment of pontics in the arch. The tissue side of the pontics was formed in a sanitary ovate shape in a way that it could be cleansable by dental floss. Proximal contacts and soft tissue contact of the pontics were assessed intraorally, and the final adjustment was done to ensure there would be cleansable embrasures and optimized soft tissue contact of the pontics to establish the physiological massage of the edentulous ridge soft tissue. The tissue edentulous as the adjusted proximal contour of the pontics was then finished and polished using the OptiDisk Finishing and Polishing system (Kerr Dental, Brea, CA, USA) in 4 sequences.
On the middle third of the palatal surfaces of pontics and abutments (from the middle of the right canine to the middle part of the left one), preparation of 2 mm incisogingival width and 1.5 mm depth to preserve the enamel substrate was performed using a round diamond bur number 1 (Figure 2(f)). The prepared palatal surfaces were etched (Scotchbond Etchant, 3M ESPE, Washington, DC, USA) for 20 seconds, then rinsed, and dried (Figure 3(a)). Total etch adhesive (Adper Single Bond 2, 3M ESPE) was applied and light cured according to the manufacturer's instructions. The pre-impregnated resin fiber strip (Interlig, Angelus, Londrina, Brazil) was adopted in prepared surfaces, covered by flowable composite resin (Universal flow, Tokuyama, Encinitas, CA, USA), and then light cured for 20 seconds on each tooth. The pontics were fixed in place with Universal flow (Tokuyama) in proximal contact areas of pontics and light cured for 20 seconds. Universal composite resin (Estelite Sigma Quick, Tokuyama) was applied and cured in some areas as needed for providing smooth contour (Figure 3(b)).
The occlusion was evaluated in centric position, protrusive, and lateral movements, and adjusted to remove heavy occlusion force in the pontics in the middle third portion where fiber was placed (Figures 3(c) and 3(d)). Then, the palatal surfaces were finished with football shape medium grit diamond bur and polished with impregnated silicon rubber points. The chronological order of all the clinical procedures is shown in Table 2.
The RBB was re-evaluated after 6 months in the point of esthetic, occlusion, soft tissue contact of the pontics, and periodontal status of abutments and restored part of retainers and pontics (Figures 3(e), 3(f), 3(g) and 3(h)). There was no sign of microleakage in the palatal surface of the retainers and pontics. Pontics showed no color change and were completely in accordance with adjacent retainers in appearance, color, and optical properties. The patient was satisfied with her smile and appreciated. Periodontal examination showed a stable condition without any mobility in abutments, and no edema, recession, or proliferation was detected in the soft tissue (Table 1). Follow-up evaluation after 1 year was still satisfactory without apparent complication (Figures 4(a), 4(b), 4(c) and 4(d)). | null | Not supported with pagination yet | null |
PMC4131807_01 | Female | 39 | The patient came to our attention at the age of 3 years for intellectual disabilities, obesity, macrosomy, and hyperkinetic syndrome of unknown aetiology. She is a female, the only child of healthy non-consanguineous 39-year-old mother and 39-year-old father with unremarkable family history. The father and mother were of normal height and weight. She was born at 41 weeks of gestation by caesarean section, due to spontaneous amniotic sac rupture without uterine contractions. Birth parameters were in range (weight: 3090 gr, length: 50.5 cm, cranial circumference-OFC: 32 cm). Apgar scores were 9/10 at '/5', respectively. The perinatal period was unremarkable with good neonatal adaptation to extra uterine environment and breast feeding; neither hypotonia nor jaundice were present. Her psychomotor development was characterised by sitting unsupported at 15 months, walking autonomously at 18 months, and uttering her first words at 18 months. The child developed obesity during early infancy, despite normal food-seeking behaviour (Additional file 1: Table S1.) and on our first examination at the age of 41 months her weight was 32 Kg (BMI = 23.59) (Figure 1A), length 128 cm ( > >97thc), OFC 51 cm (50-75thc). At the age of 3 years, she showed mild to moderate intellectual disabilities (Leiter-R scale IQ = 79) with main deficit in the verbal area, both in language comprehension and production. She was able to produce less than 10 words and unable to construct even the simplest sentences. The Vineland Adaptive Behaviour Scale (VABS) was completed by interviewing both parents. Patient's age equivalent (AE) was less than 1 year 9 months; receptive language and expressive skills score was 1 year 7 months; socialization AE was less than 1 year 11 months; daily living skills AE was 2 years 2 months; motor skills AE was 2 years 9 months.
Asynergistic walking with sole-sole pattern with feet intra-rotation due to intra-rotation of the tibia bilaterally and anteroversion of the femurs' neck has been observed.
At ocular evaluation, bilateral amblyopia (4/10) with mixed astigmatism was observed. Audiometric examination and brain-stem auditory evoked potentials resulted within normal range, with the exception of a mild delay of the 1st wave in the right ear due to mild transmission deficits.
Electroencephalograms (EEG) recording data, acquired during wake and spontaneous sleep, revealed epileptic anomalies only during profound sleep.
At last evaluation, at the age of 4 y and 4 mo, her growth parameters were: weight 39 kg (> > 97thc), length 128 cm (> > 97thc), OFC 51 cm (50-75thc), BMI 24.18 (Figure 1A). Facial examination showed slightly upturned nose and short neck without other remarkable dimorphisms (Figure 1B). Her behaviour was mainly characterised by a severe form of hyperkinetic disorder. Her attention dwelt no more than a few minutes on a single information or activity, even when she was extremely interested and highly focused on it by the examiner's intervention. Her spontaneous play activities are basically unstructured: she holds toys, explores them rapidly and superficially, then beats them. She appreciates sensory-motor experiences in play. She has no play strategies. Spontaneous interaction with relatives, other adults, and peers is poor but present. At first glance, she appears to be an autistic girl. However, when faced by the examiner and stimulated by being presented toys, she spontaneously tries to share her activities and eye contact is present. She attends kindergarten for normally developing children; however, she has a support teacher for the whole period of her school attendance. She also has a special teaching schedule and program. At present, her cognitive functioning is equivalent to moderate mental retardation with hyperkinetic syndrome. At last evaluation EEG, compared with the previous registration, is remarkably better due to a significant reduction of non-convulsive paroxysmal activity during profound sleep.
Brain MRI showed increased subdural peri-encephalic space in the frontal regions, and enlarged cisterna magna without signs of compression on the 4th ventricle or the cerebellar vermis. No other remarkable signs were evident. At abdominal echography, no pathological signs concerning spleen, liver, gallbladder, pancreas, kidneys, or bladder were observed.
Electrocardiogram (ECG) showed regular sinusoidal rhythm with 106 bites per minute, conduction and repolarization within normal limits, QT tract corrected 385 msec, and arterial hypertension; no pathological signs were evident at heart echography.
Routine haematological exams revealed increased levels of platelets (420,000 - normal range 150,000-400,000) increased triglycerides (217 mg/dL - normal range 40-150) with normal total cholesterol (143 mg/dl- normal range 120-140). Thyroid function was normal (TSH: 1.198 I1/4UI/ml (N:0.350-5000), T4:13.4 pg/ml (N:8.9-17.6), and T3: 4.8 pg/ml (N:2.3-4.2)).
Array-CGH analysis, performed with an Agilent Human Genome CGH Microarray Kit 180 k (Agilent Technologies Inc., Santa Clara, CA) with a resolution of ~40 Kb revealed a deletion of 1.9 Mb in chromosomal band 2p25.3 (Figure 2A) including the following genes : FAM110C (OMIM *611395) ACP1 (OMIM *171500), TMEM18 (OMIM *613200), SNTG2 (OMIM *608715), TPO (OMIM *608715), MYT1L (OMIM *613084) PXDN (OMIM *605158) and SH3YL1, FAM150B (Figure 2B). All nucleotide positions refer to the Human Genome, Feb 2009 Assembly (hg19). Data analysis was performed using Agilent Cytogenomics version 2.5.8.1. The deletion breakpoint, located between 1,957,657 Mb and 1,973,115 Mb (hg19), lies within intron 6 of MYT1L.
Real-time quantitative PCR (qPCR) assays, performed on the patient and her parents using SYBR Green and analysed on an ABI PRISM 7900HT sequence detection system (Applied Biosystems, Foster City, CA), demonstrated that the 2p25.3 deletion originated de novo (data not shown).
Genotyping of polymorphic locus D2S2268 in the proband and her parents, performed by amplification with primers labelled with fluorescent probes (ABI 6-Fam and 8-Hex) followed by analysis on ABI 3500AV Genetic Analyser (Applied Biosystems), revealed the paternal origin of the deletion (data not shown). The final interpretation of the rearrangement was arr[hg19] 2p25.3(30,341-1,957,657x1,1,973,115x2) dn.
Including the present case, about 18 patients, with ages ranging from infancy to adulthood and partially overlapping 2p25.3 deletions, have been described so far. All these patients share common distinctive clinical features represented by early-onset obesity/ overweightness associated with ID and behavioural troubles. The first symptom observed in our patient was very early-onset obesity (Figure 1A), starting from the 3rd month of life (Additional file 1: Table S1). A square-shaped truncal build was evident (Figure 2B), as previously reported in four patients out of six by Steven et al. and two out of five by Doco-Fenzy et al.. Her psychomotor development, resulting in mild to moderate ID, was mainly characterized by severe language delay (less than 10 words) and inability to produce sentences, even the simplest ones.
By combining genotype-phenotype analysis from all hitherto reported patients and DECIPHER cases, MYT1L has recently been proposed as the major candidate gene for ID and early-onset obesity, since the gene is deleted in all patients with terminal or interstitial monosomy of 2p25.3. The causative role of MYT1L haploinsufficiency for early-onset obesity is further reinforced by our finding, showing that our patient's proximal deletion breakpoint lies within a segment of 15,459 bp located in the sixth intron of MYT1L (Figure 2C). A very similar 2p25.3 deletion of 1.975 Mb with its deletion breakpoint within intron 5 of MYT1L has been recently reported in another patient (PZ1 from) with clinical features overlapping those of our patient, apart from neonatal hypotonia and failure to thrive. As hypothesized by Doco-Fenzy et al., ACP1 and TEM18M, usually deleted in the majority of patients with obesity or overweight, may concur to the early-onset obesity/overweight observed in patients with 2pter deletions. We may thus hypothesise that haploinsufficiency of ACP1, a gene associated with severe obesity and increased total cholesterol and triglycerides levels, may also be responsible for the increased levels of triglycerides and obesity observed in our patient.
Patients with small interstitial deletion involving MYT1L (P5, SP6 and ID25513 from) manifest behavioural troubles, including autistic spectrum disorders (ASD) while subjects with 2p25.3 terminal deletions additionally involving SNTG2 (P1-2,P4 , SP5-6 from) manifest aggressiveness and outbursts.
Our patient carrying a 2p25.3 deletion spanning nine genes, including SNTG2 and MYT1L (Figure 2B) manifests neither ASD nor aggressiveness and outburst. Her spontaneous interaction with relatives, other adults, and peers is poor but present and, if stimulated, she spontaneously tries to share her play activities. Her behaviour is mainly characterised by a severe form of hyperkinetic disorder. Overall, hyperactivity appears to be the main behavioural trait observed in patients with 2p25.3 monosomy. | deletion 2p253, hypekinetic disorder, language delay, myt1l, obesity | Not supported with pagination yet | null |
PMC9251553_01 | Female | 84 | An 84-year-old female with Child-Pugh class C liver cirrhosis due to hepatitis C presented with a progressive bulging of the anterior chest wall for two weeks. She has not been exposed to soil, gardening, and construction sites. She had not gotten any medical procedures. She denied fevers or chills, productive cough, hemoptysis, changes in weight, or loss of appetite. On examination, there was no dental cavity or ulcer in the oral mucosa. Heart auscultation revealed a regular rate and rhythm without a murmur appreciated. Large subcutaneous mass was on the anterior chest wall (Fig. 1, arrow). No axillary lymphadenopathy was observed. Laboratory data revealed a white blood cell 4600/muL (neutrophil 84%), hemoglobin of 9.9 g/dL, platelet count of 158 x 103/muL. Other bloodwork revealed aspartate aminotransferase of 27 U/L, alanine aminotransferase of 13 U/L, total bilirubin of 0.7 mg/dL, creatinine of 0.5 mg/dL and C-reactive protein of 7.1 mg/dl. Contrast-enhanced computed tomography of the chest demonstrated 7 cm x 7 cm x 5 cm loculated empyema with extension through the chest wall, into the anterior chest wall with rib destruction (Fig. 2). Microscopic appearance of the abscess revealed filamentous branching rods (Fig. 3, A: Gram stain, B: Kinyoun stain). Nocardia farcinica was identified using Matrix-Assisted Laser Desorption Ionization-Time of Flight. The susceptibility of antibiotics to Nocardia farcinica were shown in Table 1. She was successfully treated with trimethoprim/sulfamethoxazole 5 mg per kg per dose 3 times a day and subcutaneous debridement and eventually the empyema necessitans disappeared. But on the 81st day of hospitalization, the patient died of acute respiratory distress syndrome due to aspiration pneumonia. In general, Mycobacterium tuberculosis and Actinomyces spp. are the most common causative pathogens of empyema necessitans, and cases of Nocardia spp. are rarely seen. In general, the risk factor of Nocardia spp. is a preceding history of contaminated water or soil ingestion, and the patient did not respond to beta-lactam. N. farcinica is a clinically aggressive infection, particularly in immunocompromised patients such as lung abscess and brain abscess. Clinicians should pay attention to the possibility of nocardial empyema necessitans in immunocompromised patients. | empyema necessitans, liver cirrhosis, nocardia farcinica | Not supported with pagination yet | null |
PMC10175768_01 | Female | 8 | Our patient is an 8-year-old female who presented at five years of age with two months history of fever, erythematous rash over the forehead, fatigue, and poor appetite. The parents are consanguineous, and two siblings have a history of seizure disorder in the presence of normal brain MRI. Weight was on the 5th percentile, and height was below the 5th percentile. Physical examination showed enlarged and tender lymph nodes in the right anterior cervical and right inguinal areas with no hepatosplenomegaly. CBC showed pancytopenia with WBC 2.1 x 109/L, ANC 0.9 x 109/L, ALC 1.1 x109/L, Hb 6.8 g/dl, MCV 80 fl (normal 77-85), and platelet 67 x 109/L. The reticulocyte production index was 0.2%. A peripheral blood smear was significant for increased schistocytes, bilobulation of some neutrophils, few reactive lymphocytes, and occasional giant platelets. ESR was 17 mm/h, and CRP was 7 mg/L. PT and aPTT were normal. There was an increase in ALT (187 units/L, normal 20-65) and AST (318 units/L, normal 15-37). Otherwise, liver function tests were unremarkable. LDH was >1,000 units/L (normal 84-246). Fibrinogen was slightly low, 1.9 g/L (normal 2-4), and ferritin was >2,000 mcg/L. Triglycerides was 2.37 mmol/L (normal 0.34-1.13). The metabolic panel showed mild hypocalcemia 1.87 mmol/L (normal 2.1-2.55), hypophosphatemia 1.42 mmol/L (normal 1.45-1.78), normal urea and creatinine, and urine examination was normal. Immunoglobulin levels were normal, and quantitative lymphocyte subsets showed a slight decrease in B-cell 334/ul (normal 400-800/ul), and NK-cell 105/ul (normal 200-400/ul). ANA was 1:160 fine speckled with normal C3 and C4. Hemoglobin electrophoresis and G6PD level were normal. The infectious disease workup was negative which included negative blood and urine cultures, negative serology for CMV, EBV, HIV, HBV, and HCV, negative brucella culture, negative aspergillus galactomannan, and negative Quantiferon test for tuberculosis. Bone marrow examination showed hypocellular marrow with a marked increase in histiocytes, occasional hemophagocytic activity, and markedly reduced granulopoiesis. Echocardiogram was normal. Ultrasound abdomen showed mildly swollen kidneys with a mild increase in cortical echogenicity. The patient was diagnosed with hypothyroidism and was started on levothyroxine.
The fever persisted despite broad-spectrum antibiotics (piperacillin-tazobactam and amikacin) and anti-fungal therapy (amphotericin B). There were intermittent episodes of hypertension (maximum 138/84 stage II). Neurological assessment was normal. The ophthalmology exam was normal. A brain computerized tomography scan was performed because of headache. It showed a faint subcortical calcification at right frontal lobe and almost symmetrical calcification within the basal ganglia. Brain magnetic resonance imaging showed bilateral symmetrical globus pallidus, high T1 signal intensities, and a few scattered nonspecific fluid attenuated inversion recovery (FLAIR) hyperintensities in subcortical and deep white matter. There was mild generalized brain atrophy, Figure 1. The patient fulfilled the modified criteria of HLH 2009 but did not fulfill the diagnostic criteria for HLH-2004; only four criteria were present: fever, pancytopenia, Ferritin >= 500 mcg/L, and hemophagocytic activity in the bone marrow. However, there was no splenomegaly, triglycerides >=3 mmol/L, or low fibrinogen. NK-cell activity and soluble CD25 were not assessed. Thus, HLH therapy was not started. Nevertheless, immune dysregulation disorder was suspected, and we started IVIG (1 g/kg) as an immune modulating agent was administered starting on day 16 of admission and was repeated regularly every 3-4 weeks. This has led to the resolution of fever, improvement of blood count parameters and normalization of liver enzymes. However, the ferritin level remained relatively high at 735 mcg/L, Figure 2. CBC showed WBC 3.7 x 109/L, ANC 1.5 x 109/L, ALC 1.5 x109/L, Hb 9.9 g/dl, and platelet 306 x 109/L. The reticulocyte count was 2.1%. ALT was (56 units/L) and AST (was 79 units/L). The patient was discharged in stable condition with a plan to administer IVIG monthly. The child remained afebrile with no significant events for six months, then was again admitted with fever (38-39 C), oral ulcers, pancytopenia, ferritin >2,000 mcg/L, LDH >1,000 unit/L, ALT 147 units/L, AST 508 units/L, and normal fibrinogen. The infectious disease workup was again negative. The patient was started on pulse methylprednisolone 30 mg/kg for three days given the concerns of secondary HLH due to autoinflammatory disorder, then continued on 2 mg/kg. Subsequently, whole exome sequencing (WES) was requested given the concern of inherited immune dysregulation disorders or HLH which revealed a novel heterozygous missense TREX1 mutation NM_016381.3:c.223G > A p.(Glu75Lys) which is located in N-terminal catalytic domain and this amino acid change is predicted to impact the protein stability. This variant was not reported in the genome aggregation database, exome sequencing project, and 1,000 genome project. In silico prediction was performed to assess the effect of this variant; it is predicted to be pathogenic by Align-GVGD C55 and disease-causing by MutationTaster. Thus, a diagnosis of autosomal dominant TREX1-related disorder such as AGS was considered, and the patient was started on ruxolitinib, 5 mg orally twice daily as an emerging treatment option for interferonopathies. Steroids were tapered off, and the patient is no longer on IVIG for more than one year, Figure 2. The patient is still on ruxolitinib for more than two years. Most recent blood work while on ruxolitinib showed CBC: WBC 4.7 x 109/L, ANC 1.8 x 109/L, ALC 2.3 x109/L, Hb 12.8 g/dl, and platelet 438 x 109/L. Ferritin 90 mcg/L. Interferon signature was not measured. During treatment with ruxolitinib, no signs of autoinflammation were observed. The treatment was well tolerated, with no serious side effects. Segregation analysis of the family was not performed based on parental preference. | jak—stat signaling pathway, trex1 gene, child, pancytopenia, ruxolinitib | Not supported with pagination yet | null |
PMC3529438_01 | Male | 28 | A previously healthy 28-year-old man with a history of extensive plaque psoriasis on treatment with subcutaneous adalimumab for over two years presented to the infectious diseases clinic with a two month history of low-grade fevers, myalgias, and a severe nonproductive cough. The patient had been treated with a course of doxycycline followed by azithromycin approximately one month earlier, causing temporary improvement in his symptoms.
The patient had emigrated from Vietnam 11 years previously. The patient's grandfather had been treated for pulmonary mycobacterium tuberculosis (MTB) in Vietnam 15 years previously, and the patient had been treated for latent tuberculosis with nine months of isoniazid in 2004. The patient lived in Washington, DC, worked in a healthcare setting, was a nonsmoker, had no pets, and had never received a pneumococcal vaccine.
Outpatient evaluation by a pulmonologist three weeks previously included unremarkable laboratory studies and clear chest X-ray. On evaluation in our clinic, the patient was noted to be nontoxic appearing and able to speak in full sentences. His temperature on initial evaluation was 37.2 C, blood pressure 109/73 mmHg, heart rate 85 beats per minute, and respiratory rate 14 breathes per minute. His lung examination was unremarkable with clear breath sounds bilaterally without rhonchi or wheezes.
A computed tomography (CT) scan of the chest performed the same day showed a 1.1 cm lobular opacity in the right lower lobe, a moderate right pleural effusion (Figure 1), hilar lymphadenopathy, and a small amount of perihepatic and perisplenic ascites. Due to the concern for tuberculosis, the patient was admitted to the hospital for further evaluation.
On hospital admission, his temperature was 39 C, blood pressure 121/87 mmHg, heart rate 95 beats per minute, and respiratory rate 22 breathes per minute, with an oxygen saturation of 97% on ambient air. Physical exam was notable for bilateral crackles in his lungs and a diffuse psoriatic rash. A CT scan of the abdomen and pelvis performed with intravenous contrast revealed diffuse nodularity of the omentum and peritoneal lining (Figure 2), raising the concern for tuberculous peritonitis (TBP).
On the second hospital day, the patient underwent an unremarkable bronchoscopy and a thoracentesis which revealed serosanguinous pleural fluid. The pleural fluid was exudative with an 80% lymphocytic predominance. No acid fast bacilli (AFB) were seen. The pleural fluid adenosine deaminase (ADA) was elevated at 110.3 u/L. A subsequent percutaneous peritoneal biopsy was performed revealing bloody peritoneal fluid. Grocott's methenamine silver stain, AFB stain, Fite's stain, and mucin stains on the fluid were negative. Surgical pathology revealed necrotizing granulomatous inflammation with no AFB seen on Auramine-rhodamine stain. The patient was empirically started on isoniazid, rifampin, pyrazinamide, and ethambutol based on the imaging and pathology results.
The patient underwent an abdominal laparoscopy one week after admission in an attempt to make a definitive diagnosis. This revealed extensive peritoneal and omental studding measuring 2 to 3 mm in size. A modest amount of bloody ascites was present. Pathology revealed granulomatous inflammation and one AFB on Fite's stain but no AFB on Auramine-rhodamine stain. Growth of MTB complex was noted from the percutaneous peritoneal biopsy after 16 days, and subsequently all other culture specimens showed growth by day 30. Sensitivities revealed no antimicrobial resistance.
The patient was continued on his four drug MTB therapy, but the rifampin was discontinued after 2 weeks due to drug-induced hepatitis. Once his hepatitis had resolved, the rifampin was restarted without further transaminitis. He completed 2 months of directly observed therapy with isoniazid, rifampin, pyrazinamide, and ethambutol and a further 7 months of isoniazid and rifampin. He has made a full recovery. | null | Not supported with pagination yet | null |
PMC4899587_01 | Female | 0 | A nine-month-old female presented with one-week history of cough, catarrh, and fever at a referral hospital where she was admitted and treated for pneumonia. On discharge after two weeks of treatment, signs of respiratory distress persisted. Recurrent and worsening dyspnea was observed over a two-month period with repeated admissions. When an ordered chest X-ray showed left upper lobe consolidation and collapse, patient was started on anti-Koch's therapy. Mantoux and erythrocyte sedimentation rate test results were 5 mm and 65 mm/hr, respectively, while tests for HIV I and II were negative. She had no history of contact with anyone with chronic cough or tuberculosis and vaccinations were up to date. There was no family history of asthma or atopy, but history of poor weight gain was present. Echocardiography ordered on account of persistent dyspnea showed a small secundum atrial septal defect which subsequently closed after 6 months.
Following 12 months of anti-Koch's therapy, an evaluation at the referral hospital revealed respiratory distress and persistent poor weight gain with weight of 8.5 kg at two years. Chest auscultation revealed widespread rhonchi and crepitations. There was no cyanosis and a repeat chest X-ray showed a hyperinflated right lung field with left upper lobe collapse and left mediastinal shift (Figure 1).
Patient was referred to our hospital for further management. The anti-Koch's therapy was discontinued and other diagnoses such as bronchial asthma, foreign body aspiration, or congenital lung malformation were entertained. The cardiothoracic surgical unit (CTSU) was involved in the management and a requested chest CT scan showed collapse consolidation of the left upper lobe with extensive air bronchogram and compensatory hyperinflation of the right upper lobe (Figure 2). A decision to do a lobectomy was taken by the CTSU, and, at 2 years of age, she underwent left posterolateral thoracotomy and left upper lobectomy. Findings at surgery were a collapsed nodular left upper lobe, left hilar and perihilar lymphadenopathy, and healthy-looking hyperinflated left lower lobe. Histology revealed dense inflammatory infiltrates composed of lymphocytes, plasma cells, and few eosinophils within the bronchiolar walls, peribronchiolar soft tissue, and adjoining interstitium. The lymphoid cells were seen forming lymphoid follicles with pale germinal centres predominantly around the bronchi and bronchioles. Some of the bronchioles contained inflammatory debris, and plugs of granulation tissue composed of fibroblasts within a myxoid stroma were seen within the bronchiolar lumens, alveolar ducts, and associated alveolar spaces (Figure 3). Areas of haemorrhage were also seen. A diagnosis of follicular bronchiolitis was made. Postoperative period was uneventful and she was discharged home with no complications. She remains symptom-free a year after the surgery and currently weighs 12 kg at 3 years. | null | Not supported with pagination yet | null |
PMC8385714_01 | Male | 80 | An 80-year-old man was referred to our clinic due to a 6-year history of PV. He previously received treatments with systemic corticosteroids and immunosuppressants, including azathioprine and mycophenolate mofetil, both pre-maturely interrupted after 6 and 4 months, respectively, due to inefficacy. A cycle of rituximab, followed by two maintenance administrations 6 and 12 months later, had revealed effective in establishing a prolonged remission off-therapy for about 2 years. He had an episode of thrombophlebitis of the lower limbs 2 years earlier, for which he was on treatment with rivaroxaban. At the time of the first dermatological visit, the physical examination showed erosions mainly affecting the trunk and scalp. The Pemphigus Disease Activity Index (PDAI) was 7. Because of the low disease activity, a treatment with topical steroids was attempted.
After 4 weeks, the patient returned because of a significant worsening of his cutaneous lesions, which were enlarging and increasing in number, located in the head and neck, trunk, and limbs, with no mucosal sites involved. Pemphigus exacerbation was associated with the onset of other symptoms, including a progressive dysphagia, weight loss, and melena. A periodic re-assessment of serum autoantibody concentration also indicated a significant increase in both anti-Dsg1 and anti-Dsg3 antibody titers. An endoscopic examination of the distal esophagus indeed revealed a stenosing esophageal mass; a PET/CT scan confirmed the presence of a lesion 3 cm in diameter, highlighting metabolic activity areas corresponding only to tumor location, without nodal or distant metastasis (Figure 1). Previously, the chest RX and abdominal ultrasound conducted as screening for immunosuppressive treatments 2 years before were unremarkable, as well as the routine blood tests performed at that time.
The Gastrointestinal Surgery Unit opted for endoscopic resection of the tumor. In order to rule out paraneoplastic pemphigus (PNP), blood samples were collected for indirect immunofluorescence (IIF) on rat bladder and normal human skin and immunoblot for anti-plakin and anti-desmocollin autoantibodies, which resulted negative (Figure 2; Supplementary Figures 1-3).
Before the surgical intervention, delayed due to the COVID-19 outbreak, PV was managed with two cycles of intravenous immunoglobulins (IVIg, 2 g/kg per cycle) 4 weeks apart. The prolonged treatment with systemic steroids before major surgical interventions is associated with a significant risk of surgical complications; thereby, systemic steroids were not administered. After two cycles of IVIg treatment, the PDAI score remained stable.
The patient underwent robot-assisted Ivor-Lewis esophagectomy with latero-lateral anastomosis and jejunostomy feeding tube (J-tube) placement. Tissue perfusion and esophagogastric anastomosis evaluation with the indocyanine green method were performed. After the surgery, the patient achieved early mobilization, with no signs of anastomotic leak at endoscopies and CT scan. The post-operative course was uneventful, except for an episode of atrial fibrillation, which was managed with two subsequent doses of verapamil according to the advice of the cardiologist. The patient was then discharged on post-operative day 11, with no dysphagia nor nausea reported. The histopathologic examination of the esophageal mass confirmed the diagnosis of gastric cardia adenocarcinoma.
Despite the successful surgical management of the tumor, PV continued to worsen, with blisters and erosions affecting the entire body, except for mucosal sites and feet (Figure 3).
Considering the recommendation to avoid high-dose systemic steroids also after surgery, due to the risk of anastomotic leakage, the patient was managed with 4 weekly infusions of rituximab at a dose of 500 mg (lymphoma protocol). A moderate-dose systemic steroid therapy (prednisone 0.6 mg/kg/day) was started only 2 weeks later in concomitance with the end of the national lockdown.
The skin of the patient started improving progressively, with complete resolution of the lesions. The anti-DSG1 and anti-DSG3 titers likewise decreased progressively (Figure 4).
At the 4-month dermatologic follow-up, only post-inflammatory hyperpigmentation or hypopigmentation was detectable, with no active lesions (Figure 3), while the last enzyme-linked immunosorbent assay (ELISA) performed resulted in lower anti-desmoglein autoantibody concentrations. No surgery-related criticalities or tumor recurrences were highlighted during this period. | covid-19, ivor lewis esophagectomy, esophageal cancer, immunoblot, intravenous immunoglobulin, paraneoplastic pemphigus, pemphigus vulgaris, rituximab | Not supported with pagination yet | null |
PMC9167117_01 | Female | 30 | A 30-year-old woman with SLE was admitted to the emergency department because of abdominal pain.
On September 15, 2020, she developed a sore throat and cough and was subsequently treated with roxithromycin, ambroxol, and Honghua (a kind of Chinese traditional medicine). On September 17, acute and severe abdominal pain and cramping developed, with concomitant left low back pain, vomiting, and dysuria but no venting or defecation. She presented to a local hospital, where a clinical diagnosis of intestinal obstruction was made and fasting, gastric intubation, and support treatments were prescribed. The patient felt no release of abdominal pain and was transferred to the emergency department of this hospital on September 22. She had a background of pulmonary tuberculosis twenty years ago and was treated with isoniazid and rifampicin for two years. The patient was diagnosed with immune thrombocytopenia (ITP) in 2002, she suffered from frequent hemorrhage for ten years and finally underwent splenectomy in 2012, and she presented with an itchy rash on her face and limbs after exposure to sunlight in 2014. Autoantibody testing showed that antinuclear antibody (ANA) was elevated (1 : 640); Sm, SSA, RO 52, and Scl 70 antibodies were positive, while double-stranded DNS (ds-DNA) antibodies were negative. No other organ involvement was noticed. She was diagnosed with SLE and administered hydroxychloroquine (HCQ, 0.4 g/d) and prednisone (7.5 mg/d). Her last menstruation began on September 20, exactly the third day after abdominal pain developed. She denied any alcohol, tobacco, or drug abuse. Her family history was significant for lung cancer (mother died of lung cancer).
On admission, oral examination revealed oral mucosal dryness and bleeding and several lower lip mucosa ulcers. The abdomen was soft, with decreased bowel sounds, and tenderness was noticed around the bellybutton. Laboratory studies revealed hyponatremia (128 mmol/L) and increased C-reactive protein (14.07 mg/L). Liver enzymes, bilirubin, albumin, creatinine, uric acid, glucose, cholesterol, serum amylase and lipase, thyroid tests, erythrocyte sedimentation rate, and complement (C3 and C4) tests were normal. Antinuclear antibody (ANA) levels were elevated (1 : 160), SSA 60 and RO 52 antibodies were positive, and double-stranded DNA (ds-DNA) and other nuclear antigen antibodies were negative. Electrocardiogram showed sinus tachycardia. Abdominal and pelvic CT scans revealed a soft tissue signal behind the uterus and a suspicious small stone at the pelvic part of the ureter. Tramadol and chlorpromazine were administered to control the abdominal and back pain. Therapy was initiated with ertapenem (1 g/d) and methylprednisolone (0.5 mg/kg body weight) because of the infection, and the medication prescribed for SLE was suspended because of the sudden onset of symptoms. Oral laxative and intravenous infusion of 10% glucose and saline were administered due to suspicious intestinal obstruction.
The patient presented with worsening weakness and dysuria after 24 hours of admission. Reddish urine was noticed after indwelling a urinary catheter. This finding raised the suspicion of acute porphyria. The urine turned a dark brown color after one hour of exposure to sunlight (Figure 1). The urobilinogen level was 33 mumol/L (reference range, 3 to 16 mumol/L), and the uroporphyrinogen (UPG) and porphobilinogen (PBG) tests were positive. Free erythrocyte protoporphyrin (FEP) was 5.3 mug/gHb (reference range, 0 to 4.7 mug/gHb). Brain magnetic resonance imaging did not reveal any pathologic features.
Based on these findings, we made a tentative diagnosis of acute porphyria. Ertapenem and methylprednisolone were stopped as the neutrophil levels returned to normal. Sufficient glucose support (250-300 g/d), restriction of liquids (<2500 mL/d), and moderate sodium supplements were administered. Morphine (5 mg) was given to relieve pain when necessary. Hydroxychloroquine (0.4 g/d) and prednisone (7.5 mg/d) were restarted for SLE. Within a four-month follow-up, no abdominal symptoms were observed.
Based on these findings, we decided to examine the genetic causes of the disease in her family. | null | Not supported with pagination yet | null |
PMC9596802_01 | Male | 36 | A 36-years-old male patient from India was presented to our hospital with abdominal pain mainly in the left upper quadrant in association with nausea and vomiting for 1 day. He denied any history of similar attacks before, no personal history of tuberculosis, or contact with any Tb patient. Also, he had no history of previous abdominal surgeries. Upon examination, the patient's vital signs were found stable with his abdominal examination was soft with left upper quadrant tenderness. His basic blood workups were not significant, as well as his inflammatory marker was not elevated.
Initially, an abdominal X-ray was done for him, which showed non-specific bowel distribution with no air-fluid level. Then, he underwent CT of the abdomen and pelvis with intravenous contrast. It showed a small bowel cluster in the mid-abdomen with a small bowel dilation with a transition zone at the distal ileum, along with a trace amount of stool in the colon. There were no signs of bowel perforation or ischemia. The small bowel was encased by a membrane forming a sac with a small amount of free fluid in it (Figures 1A,B). The finding gives us the impression of sclerosing encapsulating peritonitis.
He underwent exploratory laparotomy with the intraoperative finding of a thick membrane covering the small bowel (Figure 2); adhesiolysis was done and the sac was excised from the small bowel to the root of the mesentery. The sac was sent for pathology review and mycobacterium culture. There was no bowel perforation or gangrene. Also, appendectomy was done for the patient anticipating difficult intraoperative access in case he had appendicitis in the future. His postoperative course was smooth without complication, diet advanced as tolerated, and he was discharged on postoperative day 5.
He was last seen in the clinic 3 months after the surgery; he was symptom free with his wound healed very well. The pathology report showed a fibrocollagenous membrane with chronic lymphocytic inflation. Mycobacterium culture was negative. | abdominal cocoon, idiopathic, intestinal obstruction, peritoneal encapsulation syndrome, primary, sclerosing encapsulation peritonitis | Not supported with pagination yet | null |
PMC9596802_02 | Male | 26 | A 26-year-old patient from India, not known to have any chronic medical illness, presented to our ER department complaining about generalized abdominal pain for 5 days associated with nausea and vomiting for 1 day. He had a similar episode 5 months ago, which got resolved spontaneously. He denied any personal history of Tb or contact with any Tb patient. Also, he had no history of previous abdominal surgeries. Upon examination, the patient's vital signs were found stable, and his abdominal examination was distended with left- and right-upper quadrant mild tenderness without any sign of peritonitis, and digital rectal examination revealed an empty rectum with no mass. His basic blood workups showed high WBC, reaching 18.8 (k/ul), as well as his inflammatory marker was elevated.
Initially, an abdominal X-ray was done for him, which showed non-specific bowel distribution with no air-fluid level. Then, he underwent a CT of the abdomen and pelvis with intravenous contrast. It showed multiple dilated fluid-filled small bowel loops in the center of the abdominal cavity with thin, soft tissue non-enhancing capsule encasing the small bowel loops with mesenteric congestion involving small and large bowel loops with a small amount of free fluid in it (Figure 3). The finding gives us the impression of sclerosing encapsulating peritonitis.
He underwent exploratory laparotomy with the intraoperative finding of thick membrane covering the small bowel (Figure 4); adhesiolysis was done and the sac was excised from the small bowel to the root of the mesentery. The sac was sent for pathology review and mycobacterium culture. There were no bowel perforation or gangrene. His postoperative course was smooth without complication, diet advanced as tolerated, and he was discharged on postoperative day 5.
He was last seen in the clinic 3 months after surgery; he was symptom free with his wound healed very well. The pathology report showed a thick fibrocollagenous membrane with chronic lymphohistocytic infiltrate. Mycobacterium culture was negative. | abdominal cocoon, idiopathic, intestinal obstruction, peritoneal encapsulation syndrome, primary, sclerosing encapsulation peritonitis | Not supported with pagination yet | null |
PMC5779785_01 | Female | 65 | A 65-year-old female (Fig. 1A, individual I-2) was referred to the Department of Internal Medicine, Daejeon St. Mary's Hospital (Daejeon, Republic of Korea) for a further evaluation. She had been diagnosed as hemolytic anemia 30 years ago, based on a medical history of persistent anemia and hyperbilirubinemia for several years. She received RBC transfusion several times and a cholecystectomy roughly 20 years ago before without knowing the reason for the operations. The laboratory findings at the time of admission to our hospital were as follows: hemoglobin, 6.6 g/dL; red cell distribution width, 23.9%; reticulocytes, 22.5%; haptoglobin, <20 mg/dL; erythropoietin, 4080 mIU/mL; total bilirubin, 8.7 mg/dL; direct bilirubin, 1.9 mg/dL; and lactate dehydrogenase, 250 IU/L. Autoimmune hemolytic anemia was ruled out because irregular antibody screening, Coombs test, and cold agglutinin test were negative, even though increased osmotic fragility. On the peripheral blood (PB) smear, round, densely staining spherical-shaped RBCs (spherocytes) were frequently found about 10 to 20 cells per high power field, that lack central pallor and have a smaller than normal diameter (Fig. 1B). Pedigree analysis of the proband's family members revealed that her 3rd son (Fig. 1A, individual II-3) showed similar symptoms such as anemia and jaundice, 2 grandchildren (Fig. 1A, individuals III-1 and III-2) experienced neonatal jaundice after birth (Table 1). Numerous spherocytes were frequently found in the PB smears of symptomatic family members. Based on these laboratory findings and clinical manifestations, the proband and symptomatic family members were provisionally diagnosed as HS. At 2 years later, the proband underwent a splenectomy due to transfusion-refractory anemia and splenomegaly. After the splenectomy, her hemoglobin level improved to normal range (14.1 g/dL) and her bilirubin levels decreased dramatically (total bilirubin 1.9 mg/dL; direct bilirubin 0.6 mg/dL).
To confirm the genetic cause of HS, genetic testing using targeted NGS that consists of genes related anemia and bone marrow failure syndromes was performed in the proband. The gene panel included 5 HS-associated genes such as ANK1 (HS type 1, OMIM 182900), SPTB (HS type 2, OMIM 616649), SPTA1 (HS type 3, OMIM 270970), SLC4A1 (HS type 4, OMIM 612653), and EPB42 (HS type 5, OMIM 612690). All subjects provided written informed consent for clinical and molecular analyses, and the study protocol was approved by the Institute Review Board of the Catholic University of Korea.
Briefly, genomic DNA was extracted from the PB. Capture of the target regions was performed with reagents from a custom design HaloPlex Target Enrichment kit (Agilent Technologies, Inc., Santa Clara, CA). Massively parallel sequencing was performed on the Illumina HiSeq 2000 platform (Illumina, Inc., San Diego, CA). Average coverage of depth of the entire panel was 101x, and 98.3% of targeted bases were covered by 10x sequence reads. Sequence reads were aligned to hg19 with Burrow-Wheeler Aligner (version 0.7.12, MEM algorithm). Duplicate reads were removed by using Picard-tools1.96. Local realignment and base quality recalibration were done by the Genome Analysis Toolkit (GATK ver 3.5). Variant calling was performed by GATK HaplotypeCaller. Variants were annotated by SnpEff ver 4.2. As a result, 1 heterozygous nonsense mutation, c.1956G>A; p.Trp652* (reference sequence: NM_001024858.2), was identified in the exon 13 of SPTB gene (Fig. 2). This novel mutation was not found in public population sequence databases such as 1000 Genomes Project Database, ESP6500, and ExAC, as well as in Korean population sequence databases (KRGDB, http://152.99.75.168/KRGDB/menuPages/intro.jsp). Any (likely) pathogenic variants were not identified in other 4 HS-associated genes according to the American College of Medicine and Genetics guidelines for the interpretation of sequence variation. Thus, this nonsense mutation of the SPTB was confirmed to cause HS in the proband and may affect symptomatic family members who could not be tested for the mutation. | null | Not supported with pagination yet | null |
PMC9540195_04 | Female | 28 | Subject 4: 28-year-old female, futsal player. She plays as a wing player. He trains 4 days per week, averaging 8 h per week. He suffered a torn meniscus, which forced him to miss 22 training sessions and 6 games in a row.
The psychological assessment instruments used for the study were:
Personal and sports variables questionnaire. Ad hoc questionnaire to collect the athlete's socio-demographic data (see Annex I).
History of sports injuries. Ad hoc created questionnaire, based on an injury protocol. It captures the number of sports injuries sustained in the last two seasons and specific data about them (see Annex II).
Profile of Mood States (POMS,). In its Spanish version adapted and validated by. It is a self-report questionnaire for measuring mood. The short version was used, with 29 items answered on a Likert-type scale with 5 response options. It includes 5 dimensions: Tension (alpha = 0.83); Depression (alpha = 0.78); Anger (alpha = 0.85); Vigor (alpha = 0.83); Fatigue (alpha = 0.82).
Depression, Anxiety and Stress Scale-21items (DASS-21,). In its version adapted and validated in Spanish. Has been used to measure general symptoms of depression, anxiety and stress. This scale has three subscales: depression, anxiety and stress, each consisting of 7 items, for a total of 21. In a Likert-type response scale, each item has four response options. It has a Cronbach's Alpha of 0.81.
Psychological Readiness of Injured Athlete to return to sport (PRIA,). The assessment instrument consists of 10 questions/items that include statements about self- confidence, individual status, uncertainty and fear of relapse. Scores range from 1 to 5, with higher scores corresponding to better psychological disposition.
Prior to the psychological assessment, the rehabilitation staff Football Federation of the Region of Murcia (FFRM) was contacted directly, thanks to a collaboration agreement in place at the time between the University of Murcia (UMU) (an organization in which the psychologist in charge of the study worked) and the FFRM. The rehabilitators served as a link between the psychologist and the athletes, providing the contact details of those athletes who met the inclusion criteria. The purpose of the study and the procedure were explained to the rehabilitators and later to the participating injured athletes (via telephone). In addition, all participants were informed of the purpose of the study and the confidentiality of both their responses and previously collected data. Informed consent and the privacy document were obtained from all participants. The entire evaluation process and subsequent contact was conducted online.
The study was approved under research ethics by the Ethics Committee of the University of Murcia (Spain), with reference number CEI-2623-2019. The moment the athletes were medically discharged from the FFRM, the psychological evaluation by the psychologist in charge of the project began. The evaluation was done online and consisted of three different moments related to the return to play (RTP), so the psychological evaluation process was as follows:
Initial assessment. It's conducted immediately after medical discharge. At this time, an assessment battery consisting of personal and sports variables, PRIA questionnaire and POMS questionnaire was used. For this purpose, an assessment battery was sent online via email, which could be completed directly by clicking on the link.
Monitoring of training. Completed once a week after practices. Recording the date and time of training, as well as the POMS.
Tracking of games. Completed after each match in which the athlete was used. Recorded the POMS, the DASS-21 and the PRIA.
It should be noted that the evaluation process was interrupted earlier than planned when competitions and training were interrupted due to the state of alert and lockdown declared by the Spanish Government because of the Covid-19 pandemic.
Descriptive statistics were used for data analysis, employing counts, sums, percentages and measurements. The results of the POMS questionnaire were converted to a scale of 0 to 100 points, with 50 being the mean. Participants' pre-competition mood profile were analyzed and described. The graphs of the pre-competition and pre-training mood profiles were created. Likewise, the graphs were made with the results of the PRIA questionnaire. The statistical program SPSS 22.0 was used. | rtp, iceberg profile, psychological readiness, recurrence, sport injury | Not supported with pagination yet | null |
PMC6586950_01 | Male | 65 | A 65-year-old man presented to our hospital with a cough. The patient was a current smoker. High resolution computed tomography (HRCT) revealed a 28 mm mass shadow in the left lower lobe and enlargement of left hilar, mediastinal, and right subclavian lymph nodes (Fig. 1A). EBUS-TBNA biopsy was performed on the subcarinal lymph node. The patient was diagnosed with left lower lobe lung adenocarcinoma with cT3N3M0 and stage IIIB. Cancer cells showed EGFR wild type and were negative for anaplastic lymphoma kinase (ALK). Immunohistochemical expression of PD-L1 in the EBUS-TBNA biopsy was 98% (Fig. 2A and B). The patient had bilateral deep vein thrombosis (DVT) of the lower limbs and pulmonary microembolism, but he did not show exertional dyspnea and status 0 according to the ECOG Performance Status. The tumor shadow was 40 mm in the largest diameter on chest HRCT performed on the day before pembrolizumab treatment (Fig. 1B). Pembrolizumab (200 mg IV over 30 min) was initiated 22 days after the first visit. The patient's pulse oxygenation on room air worsened from SpO2 98%-90% two days after pembrolizumab administration. On chest HRCT, the primary tumor shadow increased in size to 57 mm, with growing of ground glass shadows (Fig. 1C). Serum KL-6 and lactate dehydrogenase (LDH) levels did not increase. Antibiotics were initiated as we suspected bacterial pneumonia; however, respiratory failure worsened on day 6 after pembrolizumab administration. We suspected interstitial lung disease (ILD) caused by pembrolizumab and started steroid pulse therapy. The ground glass shadow around the tumor improved, but the primary tumor increased in size to 80 mm on chest HRCT on day 21 after pembrolizumab administration (Fig. 1D). SpO2 decreased to 93% (supplementary oxygen mask 4L) on day 21 after pembrolizumab administration. Serum tumor markers were elevated, and the lung cancer progressed very rapidly with a complication of disseminated intravascular coagulation (DIC). Pembrolizumab treatment appeared ineffective; thus, we initiated carboplatin and nanoparticle paclitaxel administration. After the unexpected appearance of significant bloody pleural effusion (Fig. 1E and F), the patient died on day 37 after pembrolizumab administration.
Autopsy was performed 8.5 hours after death which confirmed that the primary tumor of the left lung was in the hilar part of the left lower lobe. Sections showed white, firm, and solid tumor masses in the hilar part of S8 and 9 and almost the entirety of left S4 and S5. Marked thickening of the bronchial wall of the hilar region was observed in the left B8-9 and B4-5, but there was no lumen obstruction. The lymphangitic carcinomatosis was remarkable around the tumor mass and was widespread in the entire left lung. Lymphatic metastasis was observed in the left hilar, para-tracheal, mediastinal, and bilateral cervical lymph nodes. Fresh thromboemboli were found in the main pulmonary artery of the right lower lobe, and there were fresh and organized long thrombi in the right or left femoral veins, which were suspected to be the origin of the pulmonary artery thromboembolism. The lung cancer histology was aggressive mucinous adenocarcinoma and the predominant cancer histology was micropapillary pattern. Widespread alveolar spaces were filled up with cancer cells in the left upper and lower lobes. Histological examination demonstrated lymphangitic carcinomatosis, tumor thrombi in the small pulmonary veins. At autopsy, the bleeding source of left bloody pleural effusion could not be identified. It is thought that the strong lung congestion, dissemination of lung cancer that was found throughout the left pleura, and that bleeding tendency due to DIC were involved. We determined the cause of death to be respiratory failure due to widespread infiltration of lung cancer, which was brought about by HPD after pembrolizumab treatment.
We compared the PD-L1 expression rate of the cancer tissue in the subcarinal lymph node, taken by EBUS-TBNA biopsy (Fig. 2A), to the identical lymph node taken at autopsy. It was 98% in the EBUS-TBNA (Fig. 2B) and less than 1% in the autopsy (Fig. 2C). The PD-L1 expression rate was different in the portions of the primary lung cancer at autopsy, with the highest rate at 10% (Fig. 2D) and the lowest <1% (Fig. 2E). The overall expression rate of the primary tumor at autopsy was approximately 1%. A primary tumor specimen before pembrolizumab administration was not available. PD-L1 expression was measured using a prototype immunohistochemistry assay with an anti-PD-L1 22C3 antibody. | alk, anaplastic lymphoma kinase, dic, disseminated intravascular coagulation, dvt, deep vein thrombosis, ebus-tbna, endobronchial ultrasound-transbronchial needle aspiration, ecog, eastern cooperative oncology group, egfr, epidermal growth factor receptor, hpd, hyperprogressive disease, hrct, high-resolution computed tomography, hyperprogressive disease, ild, interstitial lung disease, immune checkpoint inhibitors, nsclc, non-small cell lung cancer, non-small cell lung cancer, pd-l1, pd-l1, programmed cell death ligand 1 | Not supported with pagination yet | null |
PMC5067098_01 | Male | 21 | A 21-year-old male patient presented to our department with a complaint of maxillary retrusion following bilateral cleft lip and palate. Computer-assisted preoperative simulation with 2-stage procedure combining maxillary advancement by employing distraction technique and mandibular setback surgery was planned. The patient was subjected to CT scan of the face using 320-row area detector CT scanner (Aquilion ONE, Toshiba, Tokyo, Japan), which acquired CT scans (slice thickness, 0.5 mm) of the maxilla. Based on the CT data, 3D surface models of the maxilla were constituted from image processing software (Mimics 16.0; Materialise, Leuven, Belgium). The cephalometric analysis and 3D planning were done using simulation software to obtain a normal profile and occlusal relationship. The 3D inspection and metrology of the maxilla was constituted using Geomagic Qualify (Geomagic, North Carolina, USA) and FreeFrom plus 2014 software (Geomagic, North Carolina, USA). The 3D models were built and superimposed through a fully automated voxel-wise method using the pre-surgery cranial base as reference. The 3D scanner (Rexcan DS2, Solutionix, Seoul, Korea) was used to obtain 3D surface data of the titanium plate (KLS Martin, Umkirch, Germany). The 3D surface data of titanium plate were imported to the Freeform Plus software (Rock Hill, USA).
In the preoperative simulation planning; the computer-assisted bone movement and positioning of the plate were carried out using 3D images (Fig. 1). The virtual Le Fort I osteotomy on the maxilla and forward movement of the virtual maxillary fragment was carried out using the Freeform Plus software. The hole was created using the virtual drill at the 3D position as computed by the preoperative simulation prior to the bone movement. The displacement distance between the points before and after the bone movement (Fig. 1A & B) and distance between the points which superimposed Lefort titanium plate of 11 mm (right) and 9 mm (left) were calculated using FreeFrom plus software. (Fig. 2). In the second step, the mandible was moved backward till the occlusal relationship was achieved.
During the real-time surgery (1st stage) Lefort type I osteotomy was carried out and the zurich pediatric maxillary distractors were placed. The distractors were adjusted on a day to day basis and the predetermined advance movement of maxilla was obtained on the 23rd day. In the 2nd stage (i.e on 23rd day) the distractor was removed and the maxillary bone was fixed using Lefort titanium plate (one Lefort plates of 9 mm, one Lefort plates of 11 mm and two Lefort plates). This enabled holding the maxilla at its advanced position and kept it stable by fixing the titanium plated to the screw holes created at the pre-designated site. The mandibular setback surgery (intraoral vertical ramus osteotomy) was performed, which manipulated the mandible and maxilla to obtain a planned normal occlusal relationship. The plate and screw position during the actual surgery and after the completion has been shown in Figs. 3-4 .
The accuracy of the simulation results was analyzed using "3D comparison" with Geomagic Qualify (Rock Hill, USA). The cranial base and zygomatic arch were used as base to superimpose the virtual plan and postoperative scan images as the base bone were unaltered during the surgery. The differences between the virtual plans and postoperative results are shown in Fig. 5. In Fig. 3A and B, the arrows show the screw positions prior to the movement of the bone while the arrows in Fig. 4A and B show the screw positions after the movement of the bone. The error of the maxillary position was noted to be less than 1 mm. The preoperative planning employing a virtual plate was found to be more reliable and less time consuming. The required time for virtual surgical planning was about 60 min. | computer-assisted preoperative simulation, maxillary distraction osteogenesis, maxillary positioning, orthognathic surgery | Not supported with pagination yet | null |
PMC5394421_02 | Female | 6 | Written informed consent was obtained from the patient's legal guardians. Molecular analysis was performed when he was 6 years old during the mother's pregnancy with her second baby. Further molecular genetic testing of the parents was performed to assess whether both variants were on the same (cis) or a different (trans) TBX19 allele and the abortion material was also analyzed molecularly. The pedigree was shown in Figure 1A.
In the molecular analysis of the index case, a novel heterozygous c.665delG (p.Arg222Lys*4) variation in exon 4 (Figures 1B,C) and pathologic heterozygous c.856C>T (p.Arg286Ter) variation in exon 6 (Figure 1D) of the TBX19 gene (NM_005149.2, NP_005140.1) were detected in the compound heterozygous state. The initial genetic test suggested a possible splice site variation (c.665 + 1delG) in intron 4 of the TBX19 gene instead of a c.665delG variant, because of the consecutive GG repeat at the exon-intron boundary. Therefore, further molecular analyses were performed at the mRNA level to gather information about the location of the variation (the last nucleotide of exon 4 or the first nucleotide of intron 4) and to identify a possible splicing effect. The mRNA analyses revealed that the real variation was c.665delG (p.Arg222Lysfs*4) and that it was a novel exonic frameshift mutation in spite of the splice site mutation (Figure 1C). As a consequence of the deletion of guanine 665 at the cDNA level, the first affected amino acid arginine was replaced with lysine at residue 222, and the new reading frame ended with a stop codon at position 4.
The other c.856C>T substitution was a nonsense variant predicted to result in the substitution of an arginine by a premature stop codon at position 286 in the protein (p.Arg286Ter) (Figure 1D). The c.856C>T variant was previously described in the Human Genome Mutation Database; it is associated with isolated deficiency of the pituitary and ACTH (HGMD #CM014746). Also, it is listed as a pathogenic allele in the dbSNP (rs74315376) and ClinVar databases,1 with a lower minor allele frequency of 0.00005 (6 of 121,334 alleles).2
Molecular analysis revealed that the mother was a carrier of the c.665delG variation (Figures 1B,C) and the father was a carrier of the p.R286X mutation (Figure 1D). The abortion material also showed the same pathological variations in the TBX19 gene. | tbx19 gene, adrenal insufficiency, adrenocorticotropic hormone, cortisol, respiratory infections | Not supported with pagination yet | null |
PMC9142782_01 | Male | 64 | Patient information: a 64-year-old man with past medical history of hypertension and end-stage renal disease on chronic hemodialysis presented with hypothermia, hyperkalemia (8.0 mmol/L), shock and delirium after missing dialysis for 3 weeks. He was noted to be in a wide complex tachycardia that was clinically a pulseless electrical activity (PEA) (Figure 1A). He received defibrillation shocks and advanced cardiovascular life support (ACLS) protocol ensued. He received calcium chloride, sodium bicarbonate, dextrose boluses and insulin. There was transient reappearance of p-waves after the administration of these temporizing therapies for hyperkalemia (Figure 1D), supporting a diagnosis of sinoventricular rhythm. However, the patient required emergent hemodialysis for a more definitive therapy and epinephrine drip for shock.
Clinical findings: physical exam was significant for an unresponsive patient with a thready pulse.
Timeline of current episode: the patient had previous history of missed hemodialysis with associated hyperkalemia and uremic encephalopathy, but this was the index event of an associated ventricular arrhythmia.
Diagnostic assessment: scheduled pulse checks were done during the ACLS resuscitation. Echocardiography images were obtained concurrently during the pulse check periods to rule out other acute structural cardiac anomaly.
Diagnosis: pulseless electrical activity with a wide complex tachycardia is considered as a cardiac arrest. Clinical considerations include ventricular tachycardia (VT), accelerated idioventricular rhythm, cardiac tamponade, hypovolemic shock, hyperkalemia, severe acidosis, hypothermia, hypoxia, pulmonary embolism, pneumothorax, and myocardial infarction.
Therapeutic interventions: CPR was resumed, and echocardiographic images were obtained intermittently during the pulse check intervals. The first images from standard apical 4-chamber view were recorded about 38 minutes before the patient was pronounced dead. The beginning images showed severe biventricular hypokinesis, LVEF approximately 20%, bi-atrial enlargement, severe mitral regurgitation, and moderate tricuspid regurgitation (Figure 2). There was only a trace of circumferential pericardial effusion and a subtle appearance of granularity of spontaneous echo contrast (SEC) noted in LV chamber only. As time progressed, there was progressive slowing of the heart rate with slightly increasing echogenicity within the LV chamber, and a nominal increase in pericardial effusion. These findings appeared unchanged until long tandem episodes of asystole heralded the last heart beats shortly thereafter. In the last 50 secs to the last heartbeat, continuous echo recording was obtained. We documented a rapid progressive echogenicity and dense thrombus formation in the LV chamber, cessation of cardiac wall motion and excursion of AV valves, followed instantaneously by the appearance of coagulation in all the other chambers (Figure 3). The AV valves appeared to be tethering with a fixed gap in mid annular-position, and an expanding rapid appearance of pleural effusion was appreciated at the end (Figure 4).
Follow-up and outcomes: the patient died during the ACLS interventions.
Informed consent: this case study is completely anonymized to protect the identity of the patient; thus, a formal informed consent was not obtained from this deceased patients. | echocardiography, cardiac arrest, case report, sinoventricular rhythm, spontaneous echo contrast | Not supported with pagination yet | null |
PMC6588134_01 | Unknown | 40 | A 40-year-oldmale presented with the complaint of pain swelling over the right elbow but no fever for the past 10 days with a history of trauma 15 days back. In the past, a history of tuberculosis (TB) of elbow treated 10 years back on antituberculosis therapy, antituberculardrugs, and surgery synovectomy debridement of elbow joint through lateral approach later patient recovered well with satisfactory result. On physical examination, there was tenderness over lateral aspect of the elbow with restricted movement of elbow and wasting of forearm muscle. Swelling over elbow with no sign of inflammation or infection skin was normal. On investigation X-ray - pathological fracture of Radial head with eccentric ballooned expanded Radiolucency margin well circumscribed lesion Bone cyst (Fig. 1). MRI -mildly expansile lesion at proximally epiphysis-metaphysis adjacent to diaphyseal location of radius extending upto sub articular location abutting articular cartilage. Surgery was planned; the aim was to excise diseased part and get good functional recovery wide excision of tumor through anterolateral approach with injection of phenol (Fig. 2). Tumor bone soft tissues send for biopsy including Radial head which was involved up to articular cartilages, (Fig. 3)Radial head reconstruction was not done because ABC extended from metaphysic - diaphysis junction to epiphysis cartilage of radial head. Post-operative recovery was satisfactory with good reasonable range of movement of the elbow (Fig. 4). | aneurysmal bone cyst, benign bone tumor, epiphysis, radius | Not supported with pagination yet | null |
PMC7395989_01 | Male | 51 | A 51-year-old male was admitted with a complaint of milky urine and significant weight loss (10 kg) for over four months. On further assessment, neither lower urinary tract symptoms nor a contact history of tuberculosis was observed. The patient was cachectic with a body mass index of 20.2 kg/m2.
Macroscopically, urine appeared milky in colours (Figure 1(a)), and the analysis demonstrated severe proteinuria and a high triacylglycerides level of 370 mg/dl (standard 1-10 mg/dl). Chloroform test for chyluria was positive, whereas filarial IgM and IgG antibodies were negative. Imaging studies of the urinary tract, which included an ultrasound scan (KUB) and CT-urography, revealed no abnormality. During diagnostic rigid cystoscopy and ureterorenoscopy, egress of milky urine from the left ureter was observed (Figure 2). The retrograde pyelogram, performed subsequently, demonstrated a left-sided lympho-urinary fistula at the level of the renal pelvis (Figure 3).
Initially, he was managed with a low-fat diet and a trial of diethylcarbamazine 6 mg/kg/day for 21 days with an inadequate response. Persistent symptoms, despite initial management, encouraged us to change over to instillation therapy. 10 ml of 0.5% silver nitrate was instilled endoscopically to the left ureter via a 6 Fr ureteric catheter, and the procedure was repeated for another three cycles at 30 min intervals. Subsequently, bladder irrigation was continued for 12 hours, and cefuroxime was administered intravenously for three days. He had an uneventful recovery with complete clearance of urine over five days (Figure 1(b)) and was discharged later on a low-fat diet. On routine follow up at one month, his urine was completely clear (Figure 1(c)), and a 3 kg increase in body weight was also observed. Follow up was carried out for twenty-two months with no recurrence of symptoms. | null | Not supported with pagination yet | null |
PMC7210922_01 | Male | 16 | Our patient is a 16-year-old male with no medical history who presented to our emergency department from another institution after being tackled in a junior varsity football game. He experienced a significant blunt trauma to the abdomen resulting in a brief loss of consciousness. He felt immediate pain in his left ankle on awakening; however, he was able to bear weight briefly until the pain became too severe. On examination, he had a generalized swelling over both the medial and lateral aspects of the left ankle compared with the right. Ecchymosis was also present on the medial side of the left ankle. He displayed tenderness to palpation over the anterolateral portion of the left ankle only. Radiographs in the anterior-posterior (Fig. 1), lateral, and oblique views revealed a Salter-Harris type IV fracture of the distal left tibia involving the posterior tibial metaphysis and the anterolateral aspect of the tibial epiphysis.
The epiphyseal fragment was displaced proximally, anteriorly, and laterally, with a 2.5 mm step-off at the articular surface seen on the lateral view. Due to high suspicion for a Tillaux fracture and inadequate evidence on plain radiographs, a computed tomography (CT) scan of the left ankle without intravenous contrast was taken. This study revealed an avulsion fracture of the anterolateral tibial epiphysis that is laterally and anteriorly displaced in addition to the non-displaced fracture of the posterior malleolus involving the metaphysis and extending into the tibial plafond with no significant step-off (Fig. 2and 3).
The decision was made to treat surgically based on the size of the articular step-off (2.5 mm) of the epiphyseal fragment. The tibialis anterior tendon and superficial peroneal tendons were marked out on the patient's skin. An anteromedial portal for ankle arthroscopy was made and the scope was inserted. A diagnostic scope confirmed the presence of a Tillaux fracture over the anterolateral aspect of the left ankle. Soft tissue was present in the fracture site so an anterolateral portal just lateral to the superficial peroneal nerve was made and a chondrotome was inserted to debride the soft tissues. A dental pick was used to hold the fracture and reduce it under direct arthroscopic visualization. K-wires held the reduction in place while radiographs were obtained to confirm the reduction radiographically. An additional K-wire was placed to be more parallel with the joint, after which the non-parallel K-wire was removed. The K-wires were removed and measured and two 4 mm cannulated screws were then inserted into the distal tibia and visualized arthroscopically and radiographically (Fig. 4, 5, 6and 7).
Final radiographs were taken and the procedure was deemed successful. The posterior malleolus fracture was also visualized on these radiographs, which was confirmed to be non-displaced. Thus, the decision was made to not use any hardware for fixation and to treat this fracture closed without fixation. The patient's left ankle was then placed in a shortleg plaster splint with instructions to remain non-weight-bearing and return to clinic in 2weeks.
At 2 weeks postoperatively, the patient was not having any significant pain and could freely move his toes in the splint. The splint was removed and replaced with another shortleg plaster splint with continued non-weight-bearing status. Ankle strengthening and range of motion exercises were allowed to take place starting at 4 weeks postoperatively, with the patient transitioned to a controlled ankle movement (CAM) walking boot and continued non-weight-bearing status. At 8 weeks postoperatively, the patient was allowed to start balancing on his left ankle for activities of daily living and weight-shifting only, with non-weight-bearing status while walking. By 12 weeks postoperatively, the patient had weaned himself out of his CAM boot and into an aircast splint though he remained non-weight-bearing. He was tolerating weight-shifting and balancing well. At this time, the decision was made to allow him to begin weight-bearing as tolerated. At 20 weeks postoperatively, he was tolerating weight-bearing while walking and had no complaints of pain. Normal strength of the ankle joint was noted with active range of motion of 30 of plantar flexion and 20 of dorsiflexion. At 1 year postoperatively, the patient had returned to participatein athletics without restrictions and reported no pain with activity. He has retained full strength of the ankle joint and had increased his range of motion to 45 of plantar flexion and 30 of dorsiflexion. Final radiographs (Fig. 8) of the ankle show the fracture healing with no loosening of hardware. | chaput fracture, salter-harris iv, tillaux fracture, volkmann fracture, adolescent, case report | Not supported with pagination yet | null |
PMC7522572_01 | Male | 68 | A 68-year-old man was referred to the endoscopy department for an oesophagogastroduodenoscopy (OGD) due to the incidental finding of a small nodule in the gastric fundus. He had a past medical history of lung adenocarcinoma for which he underwent a lobectomy in 2016. A follow-up computed tomography (CT) scan revealed a 12 mm enhancing nodule in the gastric fundus. The patient was asymptomatic and, on direct questioning, reported no upper gastrointestinal symptoms such as dyspepsia, heartburn, pain, nausea or vomit. The OGD revealed a centimetric round lesion located at the transition between the gastric fundus and the body, covered with normal appearing mucosa, compatible with a sub-epithelial lesion (Fig. 1). The remaining gastric mucosa of the fundus and the body was normal, while the antral mucosa was erythematous with small erosions. Biopsies for histology and H. pylori were taken according to the Sydney protocol (2 in the antrum, 1 at the angular incisura and 2 in the body at lesser and greater curves). Microscopic examination showed H. pylori-associated chronic gastritis in the antrum and corpus, active, with moderate glandular atrophy and multifocal intestinal metaplasia in the antrum (Fig. 2). A sequential eradication regimen was prescribed with amoxicillin followed by metronidazole and clarithromycin. H. pylori eradication was confirmed through a fecal test 2 months after the completion of the eradication regimen. To further characterize the sub-epithelial lesion, a diagnostic endoscopic ultrasonography (EUS) was scheduled. This was performed using a radial echoendoscope (GF UE160-AL5; Olympus, Tokyo, Japan) which showed a round lesion, with definite margins, homogeneously hypoechoic with visible internal vascularization, a hard texture at elastography, measuring 11 mm x 9 mm. The lesion originated from the submucosal layer (3rd layer) of the stomach with no involvement of the other layers of the gastric wall (Fig. 3). No lymph nodes were observed in abdominal and mediastinal stations. Following multidisciplinary discussion, considering the size of the lesion, its characteristics and the absence of signs of extraluminal involvement, the patient was referred for endoscopic resection. The lesion was removed using a 27 mm hot snare (Sensation; Boston Scientific, Natick, Massachusetts, USA) after submucosal injection of saline solution and methylen blue. Two metal hemostatic clips were positioned on the resection base to close the mucosal defect. The procedure was uneventful and the patient was discharged home 1 h afterwards. The specimen was sent for pathology examination. Serum gastrin and Chromogranin A levels were within normal range.
Histologic examination of the specimen revealed a 1 cm well circumscribed tumor located mainly within the submucosa layer closer to the muscularis propria. Neoplastic cells showed a predominantly trabecular to solid architecture with both nested and gyriform patterns seen focally. These cells were large with clear and granular cytoplasm and round or oval nuclei with clumped or finely granular ("salt and pepper") chromatin and small nucleoli. Numerous nodular lymphoid aggregates, some of which with germinal centers, were also seen within the tumor (Fig. 4). Mitotic activity was inconspicuous with a mitotic count of 1 mitosis in 10 high power fields (2 mm2). There was no evidence of vascular or perineural invasion. The fundic mucosa above the tumor was flattened and contained some lymphoid aggregates with germinal centers located in close proximity to the muscularis mucosae at the base of the lamina propria (Fig. 5). They were consistent with acquired mucosa-associated lymphoid tissue (MALT). There was no active inflammation with polymorph in the lamina propria or inside the glandular lumina, nor evidence of H. pylori infection. Horizontal and vertical margins were free of tumor cells.
Immunohistochemical staining showed tumor cell positivity for cytokeratin and neuroendocrine markers including Chromogranin A and Synaptophysin. Tumor cells were negative for CDX2, glucagon, insulin, gastrin, somatostatin and serotonin. Ki67 staining showed a proliferative index of 5% (Fig. 6). Lymphoid aggregates consisted of a central part of mature CD20 positive B cells surrounded by CD3and CD2 positive T cells. On the periphery of the aggregates, a fair number of plasma cells were highlighted by anti-CD138 staining.
All these findings led to the final diagnosis of a G-NET G2 pT1. | gastric neuroendocrine tumor, gastritis, helicobacter pylori | Not supported with pagination yet | null |
PMC9478668_01 | Female | 17 | A 17-year-old woman presents to the emergency department with a burning pain and swelling of her right shoulder. The patient states that the pain started a month ago, is sporadic, and is related to strain, but is not frequently felt at night. She rates her pain at a 7 on a 1-10 severity of pain scale, with 10 being the highest. She is otherwise healthy and plays on her high school basketball team. She has not had any trauma to her shoulder. The patient states that she has no systemic symptoms, including no recent weight loss or decreased movement. The patient has no personal or family history of cancer or illnesses. Social history is otherwise non-contributory. She is not on any medications. | bone neoplasia, categories of bone tumors, ewing sarcoma, musculoskeletal system, organ system pathology, pathology competencies | Not supported with pagination yet | null |
PMC4532116_01 | Male | 27 | A 27-year-old man was admitted to Yong Dong Severance Hospital, Yonsei University Medical Center, for evaluation and management of mediastinal mass.
Three years prior to admission, he found mediastinal mass on computerized tomographic (CT) scan performed in another institution.
At admission, he was noted to be with generalized weakness and right chest pain, but he denied cough, sputum and dyspnea.
The temperature was 38.6 C, the pulse rate 72/min and the blood pressure 110/70 mmHg.
On examination, he appeared chronically ill, the skin was warm and dry, the head and neck were normal and cervical lymphadenopathy was not found, the lungs were clear and the heart was normal.
The abdomen and extremities were normal.
The urine was normal and the hemoglobin was 13.5gm/dl; hematocrit 41.9%; white cell count 5,500/mm3 with 64 percent neutrophils, 35 percent lymphocytes and 1 percent eosinophils, the serum electrolytes and liver function tests were normal. T3: 150 ng/dl, T4: 7.1 ug/dl, FT4: 1.6ng/dl and TSH was 1.5 uU/ml.
The electrocardiogram showed right axis deviation and tall R wave in right precordial leads, and the sputum exanination did not suggest malignancy or tuberculosis.
Chest roentgenogram (Fig. 1) revealed well defined mediastinal mass on the right paratracheal area.
Chest CT scan revealed large multi-cystic mass lesion on the right paratracheal area which was attached to the lower pole of right thyroid gland, displaced the superior vena cava anteriorly and extended to the level of the azygous arch vein (Fig. 2).
The lung perfusion scan and whole body bone scan were normal and the thyroid scan revealed cold area in the lower pole of right thyroid gland.
The fiberoptic bronchoscopy revealed extrinsic mass effect without mucosal lesions on right intermediate bronchus.
The pulmonary function studies showed mild restriction with FEV1:2.85 L/sec and FVC: 3.49 L/sec.
He underwent operation under the impression of mediastinal mass.
8x8 cm sized mass composed of multi-cystic and solid part was located in the pericardium and excised easily from the surrounding structures and the feeding vessel maybe originated from the subclavian artery.
Grossly, the mass was composed of several cystic lesions and yellow solid lesion, resembling unexpanded lung tissues (Fig. 3) and the surface of the mass shows a feeding vessel (Fig. 4).
Mlicroscopically, the cyst wall showed a bronchial tissue which was composed of ciliated columanar epithelium, submucosal gland and cartilage (Fig. 5) and solid portion of the mass showed alveolar space filled with inflammatory cells such as macrophages or lymphocytes (Fig. 6) | null | Not supported with pagination yet | null |
PMC7350128_01 | Male | 54 | A 54-year-old nonsmoker male presented with 3 weeks of cough productive of small amounts of clear to yellow-colored phlegm, fatigue and malaise. He reported persistent fever with temperature up to 102 F and weight loss of 20 pounds over 2 weeks. He was repeatedly evaluated for these symptoms and multiple courses of outpatient antibacterials failed to improve his symptoms. He worked as a truck driver in a dumpster yard, had not traveled out of the state of West Virginia, and denied sick or animal contact or recent hospitalization. Physical examination and basic lab workup including complete blood count, chemistry panel, sputum culture, viral respiratory panel by PCR, HIV screen, Streptococcus pneumoniae and Legionella urine antigens, Histoplasma antibody panel and serum QuantiFERON TB Gold all within normal. Chest x-ray showed mild interstitial prominence and CT chest showed multiple subpleural nodular opacifications involving all lobes bilateral (Fig. 1A).
The differential diagnosis included chronic infection, connective tissue disease or interstitial lung disease. Serologic evaluation for connective tissue etiologies showed no evidence of systemic lupus erythematosus, scleroderma, mixed connective tissue disease or vasculitis. Bronchoscopic sampling with lavage was nonrevealing. Video assisted thoracoscopic biopsies from the three right lobes were then obtained. Tissue samples cultured showed growth of Paecilomyces species in all three wedge biopsies and pathology consistent with organizing pneumonia and emphysematous changes (Fig. 1 B). Specialty lab identified Paecilomyces formosus infection sensitive to amphotericin B and posaconazole Due to the unusual presentation, immune deficiency as a contributing factor was sought and ruled out (Table 1). The patient completed a 2-week course of intravenous amphotericin B followed by 6 weeks of oral posaconazole, with resolution of symptoms. 3 months after, symptoms completely abated, and dyspnea resolved. Chest CT revealed marked improvement. | null | Not supported with pagination yet | null |
PMC6594277_01 | Female | 37 | A 37-year-old woman, gravida 2, para 0, with a suspicious tumor at the liver hilum at 21 weeks 5 days of gestation was admitted to the department of obstetrics and gynecology of our hospital. Physical examination revealed a very sick and suffering patient. The patient presented with dyspnoea, jaundice, epigastric pain, ascites, and abdominal tenderness. Orange urine and white stool were reported. There was no previous or family history of any cancer. No regular medication was reported. The patient was a former light smoker; she did not smoke during pregnancy. Magnetic resonance imaging (MRI) had been performed eight days before the patient's admission; it revealed an enlarged liver with a centrally located tumor at the liver hilum and disseminated hepatic and abdominal lymph node metastases. MRI also displayed mechanical cholestasis with dilated biliary ducts and ascites (Figure 1).
On obstetrical ultrasonography at the time of admission, the estimated fetal weight was 470 g (59th percentile), a Doppler measurement of blood flow through the uterine arteries was performed, and the median PI (pulsatile index) was below 1.5. Fetal movements, fetal anatomy, placenta, amniotic-fluid volume, and the length of the cervix (40.0 mm) were normal.
At the time of the patient's initial presentation, laboratory results showed severe normocytic normochromic anemia with haemoglobin level 6.7 g/dl and hematocrit 20.2%, leukocytosis with a white blood cell count of 14.47 G/l, and a normal platelet count. Liver function parameters were elevated as follows: total bilirubin 16.64 mg/dl, glutamate oxaloacetate transaminase (GOT) 70 U/l, glutamate pyruvate transaminase (GPT) 42 U/l, and gamma-glutamyl transferase (GGT) 90 U/l. Cholinesterase was <1 kU/l; both alkaline phosphatase (843 U/l) and lactate dehydrogenase (LDH) (635 U/l) were elevated. Total protein and albumin levels were reduced (52.5 g/l, 28.0 g/l, respectively). Blood coagulation analysis resulted in a prothrombin time of 34%; an activated partial thromboplastin time (APTT) was 45.1 s. Fibrinogen (279 mg/dl) was normal. A high level of C-reactive protein (CRP) (8.23 mg/dl) was detected. Common kidney function parameters and serum electrolytes were normal. These laboratory findings are shown in Table 1. Tests for viral hepatitis B and hepatitis C and HIV were all negative.
Acute hepatic failure was diagnosed. According to the findings, the patient underwent a percutaneous transhepatic biliary drainage (PTBD) (Figure 2). Pathological examination of the liver-biopsy specimens, obtained at PTBD, revealed a poorly differentiated, diffusely infiltrating SRCC, grade 3 (Figure 3). By immunohistochemistry, the tumor was positive for cytokeratin (CK) 7 (Figure 4(a)). Tumor cells were negative for CK20, caudal-type homeobox transcription factor 2 (CDX2), estrogen receptor (ER), progesterone receptor (PR), PAX8, and human epidermal growth factor receptor 2 (HER2). Positive expression of programmed death-ligand 1 (PD-L1) was found in 30% of the tumor cells. Immunohistochemistry of phosphatase and tensin homolog (PTEN) was weak and not conclusive. In conclusion, histomorphology and immunohistochemical findings argued for a primary tumor of the upper gastrointestinal tract. DNA repair proteins like MLH1, MSH2, MSH6, and PMS2 were positively expressed. Thus, these findings argued against microsatellite instability. Next generation sequencing-based analysis of common targetable cancer mutations was ordered. The Ion AmpliSeq Cancer Hotspot Panel v2 (Ion Torrent ) and the Ion AmpliSeq BRCA1 and BRCA2 Panel (Thermo Fisher Scientific Inc., Waltham, MA, USA) were used for mutational analyses.
The following day, recurrence of ascites was observed. Therefore ultrasound-guided paracentesis was performed.
Two days after admission, regular labour started spontaneously at 6 am; therefore the patient was transferred to the delivery room. Immediately, the patient had rupture of membranes and delivered a female infant in pelvic presentation, by spontaneous vaginal delivery, at full 22 weeks of gestation. The baby weighed 427 g; the Apgar scores at 1, 5, and 10 minutes were all 1. The placenta seemed cleft; thus ultrasonography of the uterine cavum was performed, and no placental residues were detected. In general, loss of blood and involution of uterus were normal.
Afterwards, an abdominal CT (computed tomography) scan detected metastatic disease, a large mass located at the liver hilum (6 cm at maximum) next to the gastric cardia, hepatic metastasis, cholangiectasis, and enlarged locoregional lymph nodes, and bone metastases in the whole axial skeletal system. Additionally, the CT showed signs of a paralytic ileus; therefore a stomach tube has been inserted. A chest CT scan demonstrated a large right upper lobe mass (5 cm in diameter), appearing malignant, and bilateral pleural effusions (Figure 5).
In conjecture, histopathologic and imaging findings were most consistent with a primary signet cell carcinoma of gastric origin.
Despite antibiotic coverage with ampicillin after PTBD, the patient developed clinical signs of sepsis including tachycardia, fever, dyspnoea, and low blood pressure, along with significantly elevated procalcitonin (PCT) levels (5.12 ng/ml). PCT is used as a biomarker for the diagnosis of sepsis, and PCT is used to guide antibiotic therapy. Initially, no specific focus of sepsis was found. Accordingly, antibiotic therapy was changed by replacing ampicillin with piperacillin/tazobactam.
Blood cultures later grew Candida albicans and streptococci. Teicoplanin and fluconazole were thus added to the piperacillin/tazobactam regimen. Moreover, polymerase chain reaction (PCR) for DNA quantification of CMV revealed 1.63 x 102 c/ml. Thus, valganciclovir was administered.
Seven days after admission, an ultrasound examination of the liver demonstrated minimal intrahepatic cholangiectasis and gallbladder wall thickening. Decompression effect and clinical improvement were observed, but there was no improvement in laboratory parameters of cholestasis with bilirubin levels plateauing at 26.87 mg/dl.
Antitumor therapy was discussed: Because of her poor performance status (ECOG 3) and cholestasis, the patient was not a candidate for chemotherapy, and beyond PD-L1, no drugable targets were discovered in immunohistochemical analyses. After careful discussion with the patient and her family and after obtaining informed consent experimental therapy with pembrolizumab (200 mg as intravenous infusion) was initiated and well tolerated. Pembrolizumab represents a monoclonal antibody which binds to PD-1, blocking the interaction between PD-1 and its ligands (e. g. PD-L1). In tumor tissues, binding of PD-1 on T-cells to PD-L1 expressed by tumor cells inhibits the antitumor immune response of T-cells, thus enabling immune escape of tumor cells and neoplastic growth.
A few days later, the results from sequencing analyses were available: Sequencing results revealed a deletion in exon 19 of the epidermal growth factor receptor (EGFR) [p.(E746_A750del)], which represents a prototypical mutation characterizing as subset of adenocarcinomas of the lung. In addition, mutations of RB1 (exon 22) and TP53 (exon4) were detected. The patient did not have a BRCA1/2 mutation. Additional immunohistochemical stains ordered based on sequencing results revealed that the tumor cells were highly positive for thyroid transcription factor-1 (TTF1), which represents a useful marker in the diagnosis of tumors of thyroid or lung origin (Figure 4(b)).
Based on the mutational profile, treatment with afatinib was recommended. Afatinib shuts down the signalling activity of receptor tyrosine kinases of the ErbB family by binding to three members of the family, namely, EGFR, HER2 and HER4, and by inhibiting the transphorylation of a fourth member, HER3. Owing to her rapidly deteriorating health status, the patient was not able to commence afatinib. Despite supportive measures the patient died on the 14th day of admission.
Taken together, this pregnant woman was diagnosed with signet ring cell carcinoma which was primary assumed to originate from the upper gastrointestinal tract. In addition, liver and bone metastasis and a malignant-appearing lung lesion were observed. According to the histopathological (CK7 positive, CK20 negative, TTF1 positive) and genetic findings (mutation of EGFR, exon 19), primary SRCC of the lung was the final diagnosis. | null | Not supported with pagination yet | null |
PMC7492116_01 | Male | 45 | A 45-year old Japanese man had been admitted to our hospital with ulcerative pancolitis 10 years before presentation. Colonoscopy revealed typical features of moderate ulcerative colitis with a Mayo endoscopic subscore of 2 (Fig. 1). A histological examination of biopsy specimens revealed diffuse inflammatory cell infiltration in the mucosal layer, crypt abscess, and goblet cell depletion. He had been treated initially with 5-aminosalicylic acid (5-ASA) and prednisolone. Since the induction of remission with prednisolone, he had been treated only with 5-ASA to maintain remission. However, he eventually developed a relapse and required golimumab, a TNF-alpha antagonist, to maintain remission six months before presentation.
The patient then began to have frequent diarrhea (over 10 times a day), heartburn, abdominal pain, and distension 3 months after starting golimumab. The laboratory data showed no elevation of inflammatory response, with the following findings: C-reactive protein, 0.14 ng/mL, and erythrocyte sedimentation rate, 5 mm/h. Peripheral blood tests showed elevated white blood cells (19,000/muL), with eosinophilia (40% eosinophils, total count 7,600/muL). He had no history of food or drug allergies and no concomitant atopic disorder. Regarding the laboratory tests performed when starting golimumab, the eosinophil counts were in the normal range of 250/muL. A stool culture was negative for common pathogens and Clostridium difficile toxins A and B. Cytomegalovirus antigenemia tests were negative. Examinations of stool ova and parasites were negative. Serum immunoglobulin E levels were normal (14.6 KU/L). The results of the drug-induced lymphocyte stimulation test for 5-ASA and golimumab were both negative (5-ASA: 73 cpm with a stimulation index of 1.0%; golimumab: 100 cpm with a stimulation index of 1.5%). Contrast-enhanced computed tomography revealed edematous bowel wall thickening from the stomach to the colon with massive ascites (Fig. 2). Abdominal paracentesis revealed a large number of white cells that were predominantly eosinophils (over 95%). Esophagogastroduodenoscopy showed no specific findings (Fig. 3A, B). However, biopsy specimens obtained from the esophagus, stomach, and duodenum revealed eosinophilic infiltration at 10-15 cells/high -power field (Fig. 4A, B). Colonoscopy revealed rough mucosa, erythema, and friability, continuously from the terminal ileum to rectum, evaluated as a Mayo endoscopic subscore of 1 (Fig. 3C, D). Biopsy specimens obtained from the terminal ileum to the rectum revealed eosinophil infiltration at 30-100 cells/high-power field (Fig. 4C, D).
Based on these findings, the patient was diagnosed with EGE with ulcerative colitis. He started prednisolone 40 mg/day (Fig. 5). His abdominal symptoms dramatically improved, and the ascites disappeared. Eosinophil counts immediately improved to normal by three days later. The dose of prednisolone was gradually tapered over the subsequent 2 weeks, and 5 mg of prednisolone was continued for maintenance therapy. | ascites, eosinophilic gastroenteritis, prednisolone, tumor necrosis factor-alpha antagonist, ulcerative colitis | Not supported with pagination yet | null |
PMC3307466_01 | Unknown | 45 | A 45-year-old multipara presented with vaginal discharge, dysfunctional uterine bleeding (DUB) and mass per vagina. Per-speculum examination showed first degree uterine prolapse, grade II cystocele, rectocele and a cervical ulcer. Per-vaginal examination showed no significant abnormality. Patient did not reveal any present or past history of TB. Family history was not contributory. Routine cervical Papanicolaou (Pap) smear showed superficial/intermediate squamous cells with parabasal cells in a background of neutrophils. Focal areas showed macrophages, clusters of epithelioid cells and a few Langhan's type of giant cells [Figure 1]. A cytological diagnosis of granulomatous cervicitis was made. Ziehl-Neelsen (ZN) stain of the cervical smears showed acid fast bacilli (AFB), which was later confirmed by fluorescent technique and culture. Chest radiograph was not significant. The HIV status was negative. Patient did not have any kind of immunodeficiency. Patient was put on anti-TB drugs following which the symptoms resolved. | null | Not supported with pagination yet | null |
PMC7078104_02 | Female | 5 | In addition to reduced mortality, heterologous beneficial BCG effects include decreases in infectious morbidities. Case control studies in Guinea-Bissau suggest that BCG vaccination and the presence of a scar among BCG-immunized infants was associated with a reduced risk of acute lower respiratory infection (ALRI) compared to unimmunized controls, with the association being stronger for females. In fact, children with ALRI were ~3-fold more likely to have not received BCG vaccine compared to children without ALRI. Similar results were found in an exploratory analysis of national health survey data from 33 low- and middle-income countries between 2000 and 2010, where 0-5 year-old BCG vaccinated children had 17-37% lower risk of suspected ALRI compared to unvaccinated controls. A retrospective epidemiologic study in Spain used data from the Official Spanish Registry of Hospitalizations to identify differences in hospitalization rates in BCG-vaccinated children (Basque Country, where universal neonatal BCG vaccination is practiced) as compared to non-BCG-vaccinated children (rest of Spain, where BCG is not routinely used). Analysis of 464,611 hospitalization episodes over a 15-year period showed that neonatal BCG immunization was associated with fewer hospitalizations for respiratory infections (the preventive fraction, defined as the attributable proportion of disease cases prevented by BCG exposure, was 40% and statistically significant among all age groups) and sepsis (preventive fraction 36%, statistically significant among the infant group). Differences diluted with age suggesting a time-limited protective effect of BCG vaccination vs. lower rates of hospitalization for respiratory infection in older children. No significant differences in the already low mortality rates were observed.
BCG scarring has been correlated with heterologous protective effects. A recent prospective study in rural Guinea-Bissau showed that children vaccinated with the BCG Moscow strain (also known as BCG Russia) who developed a scar had 26% lower mortality compared to children who did not develop a scar, mainly attributable to prevention of deaths from respiratory infections (mortality rate ratio [MRR] 0.2). This correlation of BCG scarring and improved survival has been replicated over different time periods and with different BCG strains; however, scarification rates differ by BCG formulation. For example, BCG Russia is less likely to produce a scar compared to BCG Japan and Denmark. BCG-induced scarring in Ugandan newborns was associated with higher IFNgamma responses to heterologous stimuli (tetanus toxoid, phytohaemagglutinin) at 1 year, and differed across strains (93% with BCG Denmark vs. 64% with BCG Bulgaria vs. 52% with BCG Russia). An RCT in Guinea-Bissau showed increased scarring induced by BCG Denmark and Japan compared to BCG Russia, but no significant differences in morbidity and mortality, at least by 6 weeks of age, possibly because BCG Russia also induced relatively high scarification rates in this cohort compared to others. Even though development of scarring also depends on additional factors such as vaccination technique, preservation of the cold chain, nutritional status of the recipient, age at time of vaccination and prior exposure to non-tuberculous mycobacteria, variable scarification rates may still predict variable heterologous protection in populations vaccinated with different BCG formulations.
In adults, BCG immunization induces specific epigenetic markers associated with the acquisition of a trained or tolerant phenotype after BCG vaccination. In healthy volunteers BCG induces trained immunity and heterologous protection from infections through epigenetic reprogramming of monocytes, specifically trimethylation of histone H3 at lysine 4 (H3K4me3) at the level of cytokine and TLR4 promoters. To further characterize BCG-induced innate immune regulation, adult PBMCs were cultured with BCG in vitro. Following heterologous stimulation with TLR ligands and bacteria, there was increased production of TNF, an effect mediated through the Nucleotide-Binding Oligomerization Domain Containing 2 pathway. In a randomized placebo-controlled adult study, yellow fever virus vaccine recipients who had been BCG vaccinated with the Denmark strain 1 month prior, had significantly lower yellow fever viremia compared to subjects who had received placebo vaccination. BCG vaccination conferred protection against yellow fever experimental infection by inducing genome-wide epigenetic reprogramming of monocytes involving genes related to signal transduction molecules, epidermal growth factor receptor, fibroblast growth factor, and vascular endothelial growth factor signaling pathways, as well as genes such as AKT1, MAPKs, and PI3K-related that have been shown to be important in beta-glucan-induced trained immunity, the prototypical trained immunity-inducing agonist in vitro. This effect correlated with induction of cytokine responses indicative of trained immunity: higher pro-inflammatory cytokine production (TNF, IL-1beta, IL-6) from BCG-vaccinated volunteers, compared to placebo-treated individuals, with a crucial role for IL-1beta production and release. These observations suggest potential mechanisms for heterologous protection that could also apply to infants, as epidemiological studies have shown that BCG vaccination results in lower all-cause mortality in infants.
More recently, immune-gene priming long non-coding RNAs (lncRNAs), positioned at the nexus of RNA, DNA, and protein interactions, have emerged as key regulators of gene transcription in trained immunity by positioning themselves at the nexus of RNA, DNA, and protein interactions. Taking advantage of the three-dimensional nuclear architecture and the close proximity of functionally related immune genes in topologically associated domains (TADs), lncRNAs contribute to accumulation of H3K4me3 at the promoters of trained immune genes in human monocytes.
Growing evidence that innate immune engagement by BCG enhances responses to other pathogens raises the possibility that some, or conceivably even most, of its clinical benefit is due to heterologous effects. However, the extent, mechanism and ontogeny of trained immunity in early life remain incompletely defined. Understanding how BCG-induced innate immune engagement, including BCG-induced enhancement of Th-polarizing cytokine production by antigen-presenting cells, varies by BCG strain and age is of basic and translational importance.
Intracellular metabolism plays key roles in regulating innate immune memory. In particular, different training programs induce metabolites that function as cofactors for epigenetic enzymes, which in turn induce chromatin and DNA modifications and modulate gene transcription upon re-challenge with a second stimulus. The Warburg Effect, first described in neoplastic cells, is a metabolic pathway important to trained immunity. Under normoxia, in resting cells, there is a low level of glycolysis and preferential pyruvate oxidation in the mitochondrion (oxidative phosphorylation), which confers slow but very efficient ATP production. In activated and proliferating cells, there is a metabolic switch from a state of oxidative phosphorylation to a state of glycolysis, crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity.
Epigenetic and metabolic reprogramming of hematopoietic progenitors may account for the long-term maintenance of trained immunity. Trained immunity affects myeloid cells as well as precursor cells of the innate immune system in the bone marrow. Administration of beta-glucan in mice induced selective expansion of myeloid stem and progenitor cells accompanied by a global increase in energy metabolism in bone marrow progenitors, particularly enhancement of cholesterol biosynthesis and glycolysis. Cytokine analysis in the bone marrow extracellular fluid revealed elevated IL-1beta levels, important in shaping immunometabolism within the bone marrow. In a randomized placebo-controlled human BCG immunization study with subsequent yellow fever vaccine challenge, reduction of viremia was highly correlated with the upregulation of IL-1beta, a cytokine associated with the induction of trained immunity, but not with the specific IFNgamma response, supporting a key role for IL-1beta as a mediator of trained immunity responses. In mice, access of BCG to the bone marrow reshaped the transcriptional landscape of hematopoietic stem cells resulting in preferential myelopoiesis vs. lymphopoiesis and generation of macrophages that provided improved protection against TB.
Changes in glucose, glutamine and cholesterol metabolism enable maintenance and longevity of trained immunity via accumulation of immunologically active intermediate metabolites. Examples include: (a) cholesterol, which participates in cell membrane remodeling and increased sensitivity to subsequent stimuli, (b) succinate and fumarate, which antagonize histone demethylation and suppress anti-inflammatory genes, (c) acetyl-CoA, an essential substrate for acetylating processes, and (d) NAD+ which is important for epigenetic changes resulting in a switch from glucose to fatty acid oxidation during LPS-induced tolerance and sepsis-induced immune paralysis. Immunometabolic changes may be different between newborns and adults, reflecting the differential nutritional and metabolic needs of the two groups, as well as their distinct immune response to pathogens. Indeed the ontogeny of immunometabolism is an emerging and promising area of research (see Box 2).
Systems vaccinology, the application of global molecular techniques such as metabolomics, proteomics, or transcriptomics, can provide unique insights into vaccine-induced immune responses by identifying molecular signatures that may predict and give insight into vaccine-induced immunogenicity and protection. The systems biology can provide valuable insights into host-pathogen interaction with Mtb as well as generate tools for early and proper diagnosis of TB, identification of BCG protective efficacy, and accelerated development of better TB vaccines. The metabolome, the inventory of all metabolites present in a given sample, reflecting both genetic and epigenetic influences, shifts upon immune activation and can in turn shape immune responses. Metabolic phenotype influences vaccine immunogenicity and together with orthogonal datasets can identify correlates of vaccine immunity. Lipid metabolism is pivotal in the regulation of inflammatory signaling hence making lipidomics, an in-depth profiling of lipid metabolites, a valuable modality as well. Lipid metabolism regulates immune cells via cell membrane synthesis and is important to epigenetic reprogramming of immune cells. Mass-spectrometry-based metabolomics, together with computational tools, can identify and correlate metabolic pathways between samples, providing a powerful approach for clinical diagnostics. More studies are warranted to build the area of biomarker identification while addressing the challenges of identifying correlates of protection against TB.
BCG has been recognized as a potent immunomodulator for decades with extensive use for cancer and particularly bladder cancer treatment. In the past decade, there has been revived interest in BCG vaccine for potential new therapeutic uses in type 1 diabetes mellitus and treatment of other forms of autoimmunity. When administered to young NOD (autoimmune-prone) mice, BCG could not only stop new-onset diabetes but also reverse end-stage diabetes, owing to induction of suppressive regulatory T cell (Treg) expansion, thereby preventing the immune system from attacking the body's own tissue. In a clinical trial involving humans with longstanding type 1 diabetes mellitus, repeat BCG administration (2 doses) led to transient restoration of pancreatic cell islet function in vivo (for 4-6 weeks after vaccination). The suspected mechanism was BCG-induced proliferation of Tregs and selective elimination/suppression of auto-reactive cytotoxic T cells, possibly via TNF induction/TNF receptor 2 agonism. Long-lasting improvements in glycemic control as evidenced by sustained decreases in hemoglobin A1c were achieved via accelerated glucose utilization induced by a systemic shift from oxidative phosphorylation to aerobic glycolysis.
In a double-blind, placebo-controlled trial conducted in Italy involving subjects with early symptoms consistent with multiple sclerosis (MS), participants were randomly assigned to receive BCG or placebo and monitored monthly with brain Magnetic Resonance Imaging (MRI) (6 scans). By the end of the study, 58% of those vaccinated had not developed MS, compared with 30% of those who received placebo. Overall clinical benefits after BCG administration in new onset MS were durable and even enhanced at 5 years. In another trial, BCG vaccination was found to decrease MS disease activity and prevent progression of brain lesions in patients with relapsing-remitting MS. A phase III clinical trial of BCG to reverse progression of MS is now underway.
BCG vaccination has also been associated with a reduced risk of atopic disorders as noted in a Japanese cohort, as well as in African children, where the reduction in atopy associated with BCG was greater the earlier the age at vaccination, with the largest reduction seen in children vaccinated in the first week of life. This observation is consistent with BCG being a powerful inducer of a Th1 phenotype in infants and shifting their immune response away from the Th2-type that is typically favored in early life. Importantly, these immune polarizing effects of BCG may be yet another result of trained immunity, which may contribute to host survival in early life and affect the risks of infection, allergic and chronic inflammation later in life. A randomized controlled trial to determine if BCG immunization at birth reduces allergy and infection in infants is currently underway in Australia (Melbourne Infant Study, NCT01906853).
Few studies have investigated the influence of age at and timing of immunization on BCG-induced immunogenicity and protection against TB. BCG-specific effector CD4 T cell responses demonstrate increased antigen-specific CD4 T cell proliferative capacity in infants compared to older children. Vaccination at birth induces a broad Th1/Th2/IL-17/Treg anti-mycobacterial response but the Th1/Th17 response is reduced when delaying the vaccine from birth to 4 1/2 months of age. In a randomized trial of low birth weight newborns, BCG significantly increased in vitro whole blood cytokine responses to heterologous TLR agonists and to PPD in infants 4 weeks post-vaccination, particularly cytokines IL1beta, IL-6, TNF, and IFNgamma, potentially contributing to broad protection against infections. These studies illustrate that timing of BCG administration can be crucial for its immunogenicity with distinct effects depending on which outcomes are studied (mycobacterial-specific vs. heterologous). Mechanistic studies are needed to provide a basis for understanding the impact of immune ontogeny on BCG immunogenicity.
Comparable CD4 and CD8 T cell anti-mycobacterial responses and whole blood cytokine production were noted in Australian infants who received BCG Denmark at birth (early BCG) compared to 2 months after birth (late BCG). However, in TB-endemic regions such as Cape Town and South Africa, delaying immunization with BCG Denmark 10 weeks post-birth led to increased frequencies of memory CD4 T cells at 1 year of age. These two seemingly contradictory studies emphasize the importance of immune ontogeny, as well as genetic and epigenetic host factors, including prior and ongoing host exposure to non-tuberculous mycobacteria, to the immunogenicity of live vaccines.
BCG vaccination in children results in different cytokine induction patterns compared to adults. Vaccine efficacy rates were indeed higher in studies conducted in populations vaccinated during childhood compared with populations vaccinated at older ages. The longevity of BCG clinical effects remains largely unknown and may in part depend on age of immunization. In the largest community-based controlled trial of BCG vaccination conducted in southern India in the 1960s, vaccine recipients were reevaluated 15 years after BCG vaccination: protective efficacy in persons who had been vaccinated as children was found to be 17%, while no protective effect was seen in people who had been vaccinated as adolescents or adults.
WHO currently recommends BCG at birth for countries where TB is endemic since birth is the first point of contact for the newborn with the healthcare system. In practice, however, many healthcare systems continue to institute policies such that BCG is not administered unless a certain number of infants are present to receive immunization from the multi-dose BCG vial resulting in missed opportunities to administer it at the earliest possible age per WHO recommendations. However, based on the above, a "one size fits all" policy on optimal BCG timing may not be realistic and immunization should be tailored to different global populations with different risk factors in different settings. Further investigations involving the ontogenetic aspects of BCG-induced immunogenicity and protection against TB are needed. Highly standardized comparison studies should account for the environmental (local and regional) exposure, genetic and epigenetic factors, biological age, and immunological status of vaccinated participants. Such studies would further inform the variation of heterologous effects seen as a result of BCG vaccination.
The ability of live vaccines such as BCG to induce heterologous immunity raises the possibility of leveraging such broadly protective effects in the development of novel vaccine formulations, in the form of "trained immunity-based" vaccines. Firstly, increased awareness of innate memory may be employed to define new classes of vaccine adjuvants, crucial tools to optimize current vaccines and develop new ones. Adjuvants enhance responses to vaccine antigens by a variety of mechanisms, but like BCG, many are capable of acting via PRR signaling (e.g., TLRA), which possibly could hold the potential of inducing innate memory and could thereby mediate long-term changes in host defense. Also, recent advances in adjuvant discovery and delivery have opened up a new toolbox on how vaccinologists can employ adjuvants, including synthetic small molecule PRR agonists. Thus, to confer protective immunity a strategy might be the combination of adjuvants, with potential of inducing beneficial non-specific trained immunity responses, formulated along with the specific selected antigen epitopes. An important aspect to take into account is that it is not yet known whether or not all PRR stimuli produce trained immunity-like responses. As different adjuvants may trigger different cell activation pathways and have age-specific activity, it is likely that more than one trained immunity pathway could be targeted for perturbation. In addition, putative target cell populations for innate training may vary, including progenitor cells, tissue resident or circulating monocytes, which may be optimally targeted via specific routes of administration or by rationally selected adjuvant formulations.
Secondly, characterizing mechanisms by which BCG enhances neonatal immunity may inform rational design of scalable, synthetic subunit vaccine formulations for newborns. Initially, TLR7/8a imidazoquinolines were shown to induce trained immunity in newborn mice, raising the possibility that such an approach could generate a vaccine that may also induce "BCG-like" trained immunity. However, since free un-formulated molecules may have off target effects, another approach is to build "BCG-like" synthetic "non-live" particulate vaccines that may mimic BCG's immune-enhancing effects. Inclusion of an imidazoquinoline small molecule TLR8 agonist in a polymersome nanoparticle (~150 nm diameter) induced robust Th1 polarizing responses from human newborn monocyte-derived dendritic cells in vitro that at least matched and for some biomarkers such as IL-12p70 exceeded those induced by BCG Denmark. Of note, when co-loaded with the M. tuberculosis antigen 85B peptide 25, the TLR8-agonist containing polymersome nanoparticles were comparable to BCG in inducing antigen-specific T cell responses in human TLR8-expressing neonatal mice in vivo. This is promising, since BCG reduces the risk of disseminated early life TB safely, elicits Th1-type neonatal immune responses and requires only a single dose at or shortly after the time of birth. The key role of TLR8 agonists for protection against Mtb challenge was recently verified by others with humanized TLR8 mice and in human studies, wherein humans with hypermorphic alleles of TLR8 demonstrated enhanced BCG-induced protection against TB.
Thirdly, the robust safety and immunogenicity profile of BCG has rendered it an attractive vector for vaccine development against other infectious diseases. Recombinant BCG technology has been studied in the context of vaccination against HIV, Lyme disease, malaria, measles, and HCV. When administered in early life, BCG can act as an adjuvant enhancing antibody responses to recombinant hepatitis B surface antigen (rHBsAg) both in mice and in human infants. In another approach, a recombinant strain of M. bovis BCG that secretes high levels of functional murine monocyte chemotactic protein 3 (BCGMCP-3) attenuated vaccine virulence in immunodeficient mice, while maintaining protective efficacy against Mtb in mice by enhancing antigen-specific IFNgamma T cell responses, as compared to a control BCG (Pasteur strain 1173P2). A recombinant BCG strain expressing listeriolysin O to enhance cytosolic entry of BCG antigens for MHC I presentation, named VPM1002, induced both CD4 and CD8 responses and demonstrated safety and immunogenicity in a phase 2 clinical study in South African newborns. Overall, insights into BCG vaccine-induced heterologous and specific immunity may provide insights into the development of a broad spectrum of anti-infective vaccine formulations. | bcg formulation, immunogenicity, mycobacteria, ontogeny, trained immunity, vaccine | Not supported with pagination yet | null |
PMC9294257_01 | Male | 36 | 36-year-old Micronesian male presented with worsening left knee pain and swelling over the last seven days. His past medical history includes iron deficiency, chronic hepatitis B, and recently active TB. He described a throbbing pain encompassing his entire left knee. Additionally, he endorsed fatigue and night sweats without fevers, cough, or dyspnea. There is no personal or family history of immune deficiency. Seven months prior he was admitted to an outside facility due to left sided pyelonephritis and was found to have an abnormal CXR. Bronchoscopy and bronchial culture were positive for pansusceptible Mycobacterium tuberculosis. Fluid drained from his left chest wall abscess also grew Mycobacterium tuberculosis. At that time, urine acid-fast bacilli (AFB) stain was positive, and a left ureteral stent was placed for presumed TB-related pyelonephritis. However, urine Mycobacterium tuberculosis PCR was not performed. He was started on a four drug intensive phase regimen under direct supervision which he completed for two months. Currently, he takes isoniazid and rifampin for TB continuation phase along with Vitamin B6.
Physical exam revealed a warm, tender, erythematous left knee. Knee flexion was severely limited due to pain and he was unable to bear weight on his left leg. Pulmonary exam demonstrated normal lung sounds with symmetric chest rise. The remainder of the exam was unremarkable. Joint arthrocentesis produced bloody synovial fluid containing 8559 white blood cells without crystals. Subsequent cultures of this fluid yielded Cryptococcus. Magnetic resonance imaging (MRI) of his left knee, seen in Fig. 1, suggested infectious arthritis. Fungal cultures of his blood and cerebral spinal fluid were negative although serum Cryptococcal antigen was positive. During this admission, immunodeficiency work up revealed reduced levels of CD3(431 cells/mcl), CD4(269 cells/mcl), and CD8 (142 cells/mcl) T cells. HIV infection was ruled out with fourth-generation antibody/antigen combo testing at an outside hospital and at our institution. HIV 1 PCR was not requested.
Oral fluconazole was started and he underwent a left knee irrigation and drainage, synovectomy, and arthroplasty. Fig. 2 shows an intraoperative picture. A spacer was placed using amphotericin B and vancomycin cement. Intraoperative tibia samples obtained grew Cryptococcus as well. | coinfection, cryptococcosis, immunocompetent, lymphopenia, tuberculosis | Not supported with pagination yet | null |
PMC2825516_01 | Male | 67 | A 67-year-old man (mongoloid race, Japanese) was admitted to our hospital because of a 3-day history of fever. Acid-fast bacilli was found to be smear-positive in his sputum, and a chest radiograph and computed tomography examinations showed parenchymal opacities with scattered fine nodules in his right apical region. He was diagnosed with pulmonary tuberculosis, so he was started on anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide on the first day that he was hospitalized. He had developed a cerebral hemorrhage 18 months before this hospitalization, and he had right hemiplegia, dysphagia, and aphasia as sequelae. He had been receiving 600 kcal/day of liquid nutrition via a nasogastric tube for 6 months before the current hospitalization.
On admission to our hospital, he had a 16.5 cm x 15.5 cm, grade IV pressure ulcer in the sacral region, from which Escherichia coli and methicillin-resistant Staphylococcus were detected (Figure 1, panel A). His albumin count was 2.2 g/dL, hemoglobin was 11.1 g/dL, C-reactive protein was 12.0 mg/dL (Figure 2) and his body temperature was 38 C. A liquid nutrition of 200 kcal was administered for 60 minutes, 3 times a day, and this regimen was continued for 2 weeks. In order to improve his state of nutrition and to reduce weight-bearing on the sacral region, 1,200 kcal/day of liquid nutrition was administered for a shorter time. This, however, induced watery diarrhea and gastroesophageal reflux. His general condition and malnutrition (low serum albumin) suggested that he would have a poor prognosis if a gastrostomy was performed. It was difficult to confirm whether or not he would accept gastrostomy feeding, so nasogastric tube feeding was continued. As for the preparation, we selected semi-solid nutrition with higher viscosity (20,000 mPa x s). In order to achieve the administration in a certain short period of time, a nasogastric tube of 18 French was inserted.
As the patient was febrile and bedridden, his total energy expenditure was assessed as 1,708 kcal/day by the Harris-Benedict equation (presumed height 162 cm, presumed body weight 45 kg, ideal body weight 57.7 kg, activity factor = 1.1, stress factor = 1.5). Considering that his caloric prescription up to that time had been 600 kcal/day and he had diarrhea, we first tried 1,200 kcal/day.
On day 21 in hospital, a semi-solid enteral product of 400 kcal/267 g (PG Soft , Terumo, Tokyo, Japan) was administered for 15 minutes 3 times a day, which was then followed by 250 mL of semi-solidified water (PG Water , Terumo, Tokyo, Japan) and dietary fiber. After starting the semi-solid enteral product, he experienced no diarrhea or esophageal reflux. On day 22, a debridement of the sacral pressure ulcer was conducted. Four weeks later, an improvement was observed in his albumin, hemoglobin, and C-reactive protein levels (Figure 2). His pressure ulcer was then 8.0 cm x 5.0 cm (Figure 1, panel D).
No complication of the esophagus, paranasal sinus, or nose wings accompanying insertion of the nasogastric tube was observed. Compliance of the large-bore nasogastric tube was favorable, and he did not try to remove the tube himself. With continuous maintenance of the tube, no obstruction was observed. Administration of anti-tuberculosis drugs was continued via the nasogastric tube without any adverse effects, and tubercle bacillus was not detected in his sputa. After 3.5 months, he was transferred to another facility for further recuperation. | null | Not supported with pagination yet | null |
PMC8639281_01 | Male | 63 | The participant (C.S.) was a 63-year-old male who suffered a left hemisphere ischemic stroke 45 days prior to the study and was not receiving speech and language therapy. C.S.'s neurologist stated that he experienced mild expressive aphasia with short-term memory (STM) difficulties and verbal information processing difficulties. C.S.'s reported having difficulties remembering recent verbal information while having a conversation with family and friends. He was a retired food and beverage employee, with 12 years of education, and was a hobby farmer. Although brain damage was not visible on the current MRI (Figure 2), the initial medical MRI report indicated the presence of an acute ischemic stroke in the medial temporal lobe. C.S. lived with his wife and did not suffer any paresis or paralysis as he was able to drive and care for himself with minimal assistance.
The assessment battery was administered in a predetermined order in 2 sessions, of approximately 2.5 hours duration in total.
The Albert's Visual Neglect Test to determine unilateral spatial neglect
The Edinburgh Handedness Inventory aimed at evaluating handedness of the preferred hand for carrying out daily activities
The Greek adaptation of the Beck's Depression Inventory-II, to measure characteristic attitudes and symptoms of depression
The background tools were used to fulfil certain inclusion criteria in order to proceed to the pretesting and treatment stage of this study. A detailed case history was taken including personal and medical information. A TMS safety questionnaire was completed prior to entering the first stage of the inclusion process, followed by a screening procedure which included the following:
The Raven's Coloured Progressive Matrices (RCPM)
Subtests from the Greek version of Boston Diagnostic Aphasia Evaluation-Short Form (BDAE-SF)
The RehaCom Working Memory Screening Task
A personal stroke narrative
The Multilingual Assessment Instrument for Narratives (MAIN)
A Procedural Discourse task
The Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39)
A battery of tools was administered at baseline, immediately after treatment (same day), and 3 months posttreatment at the follow-up stage. The tools used were as follows:
The RCPM, a test used to measure abstract reasoning, is also regarded as a nonverbal estimate of Gf. The RCPM is made up of a series of diagrams or designs with a part missing, and the participant is asked to choose the shape to complete the pattern or shape from six alternatives. The Greek version of RCPM was administered as adapted by. Every correctly solved pattern was given 1 point, with a total score range between 0 and 36.
Conversational and expository speech such as simple social responses, free conversation, and picture description
Auditory comprehension including word comprehension, commands, and complex ideational material
Oral expression, such as automatized sequences, single word repetitions, repetitions of sentences, responsive naming, the Boston Naming Test-Short Form (BNT-SF), and screening of special categories
Reading, including letter and number recognition, picture-word matching, basic oral word reading, oral reading of sentences with comprehension, and reading comprehension of sentences and paragraphs
Writing, including mechanics, dictation writing of primer words, regular phonics and common irregular forms, written naming, narrative writing mechanics, written vocabulary access, syntax, and adequacy of content
The BDAE-SF has been standardized in Greek and is culturally appropriate. It includes five subtests:
For the purposes of this study, only subtests 1-4 were administered and results were analysed in accordance with the test manual.
The RehaCom Working Memory Screening module is a tool used to assess both simple WM span (simple information holding) and the retention and processing of visual-spatial information. When the WM screening task is initiated, ten dots are presented in a circular arrangement. Individual dots sequentially turn red and fade. The first sequence consists of two random dots out of the ten lighting up in a particular order to be repeated correctly. When selected correctly, the number of dots increases in the next sequence. In sum, the task is to memorize the presented sequence of dots lighting up. The WM screening subtest ends after two consecutive incorrect sequence responses or after 7 minutes. The visual-spatial memory span is measured by the maximum length of the memorized dot patterns that can be reproduced immediately without errors. Additionally, the participant's memory span is calculated based on the highest sequence length measured in number of dots, reproduced without mistakes in position and order, and it is confirmed by completing two consecutive sequences with the same number of dots.
A personal stroke narrative was elicited by asking the participant to describe how his stroke occurred. The sample was transcribed and analysed using the Shewan Spontaneous Language Analysis (SSLA) system in accordance with the SSLA protocol. Variables for analysis included number of utterances, time (total speaking time in minutes), rate (syllables per minute), length (percentage of utterances <= 5 words), melody, articulation, complex sentences (percentage of utterances that contained one independent clause and one or more dependent clauses), errors (percentage of grammatical, syntactic, or morphological errors), content units (units that conveyed information), paraphasias (percentage of substitutions), repetitions, and communication efficiency (content units/time).
a goal statement for the protagonist
an attempt by the protagonist to reach the goal
an outcome of the attempt in terms of the goal
the internal states (IST) which initiate the goal and also express reactions
The MAIN is a tool designed to evaluate narrative tell and retell skills in children but has also been used with adults with acquired language deficits associated with neurological disease for research purposes. The MAIN stories consist of coloured picture sequences developed according to strict psycholinguistic criteria. While the MAIN examines narrative production at microstructure and macrostructure levels, for this study, only the macrostructure of the generated story was analysed. The primary unit for macrostructure analysis is the episode. The content of each picture sequence was designed to represent three short episodes. Each episode consists of
Each story is controlled for cognitive and linguistic complexity and has a moral meaning similar to an Aesop fable. In this study, the "Baby Goats" story was used which portrayed a mother goat wanting to save her baby goat who jumped into the water but a fox jumped forward to catch the other baby goat. Then, a bird saw that the baby goat was in great danger and stopped the fox by biting its tail and chasing it away to save the baby goat. Six-coloured pictures in the form of a cartoon strip were presented, and one-episode was unfolded each time (2 pictures) for the participant to narrate a story based on the pictured stimuli. The scoring sheets of the MAIN "Baby Goats" story provided the scoring system used for the story structure components (setting, goals, attempts, outcomes, and IST). A setting statement, which gives time and place and introduces the story's protagonist, is scored with zero points for wrong or no response, 1 point for one correct response, and 2 points for reference to both time and place. This component is followed by three episodes. Each episode consists of (a) the internal states which initiate the goal and also express reactions; (b) a goal which is a statement of an idea of the protagonist to deal with the initiating event; (c) an attempt by the protagonist to reach the goal, which is an indication of action to obtain the goal; (d) an outcome of the attempt in terms of the goal, which is the event(s) following the attempt and causally linked to it; and (e) the internal states as reaction, which is a statement defining how the protagonist(s) feel or think about the outcome or an action resulting from an emotional response. The story output was transcribed verbatim, and it was analysed using a scoring system of 17 points for story structure components in production, following the guidelines for assessment, and guided by the information on the provided scoring sheets.
Get the bread out
Get two slices of bread//halved bread
Get the butter
Get the (rest of the ingredients, i.e., ham and cheese)
Get a knife
Put/place the bread on the plate
Put/spread butter on bread
Put the ingredients (i.e., ham and cheese) on bread
Put the two pieces together
Cut the sandwich in pieces
The Procedural Discourse task is considered a semispontaneous speech production task that assesses discourse ability following the main concept analysis (MCA) procedure. The MCA enumerates the speaker's ability to communicate the overall idea of an occasion, and it provides a way to evaluate the generated precision and completeness of the critical concepts of the shared topic. The participant was instructed to verbally provide all the required steps to be taken in order to prepare a sandwich. The generated language sample was analysed using the MCA procedure referring to the ten main concepts. The total number of main concepts expected to be produced was analysed and measured based on the concept content as listed below:
The first five steps comprise concepts concerning retrieving the ingredients needed, the following four steps include concepts concerning ingredient assembly, and the final concept describes the final appearance of the target (sandwich) prior to serving it. The procedure output was transcribed verbatim, and it was analysed using a binary scoring system of "1" for correct information and "0" for incorrect/missing information.
The SAQOL-39g has been translated and culturally adapted in Greek for use in Greece with PWA. The Greek SAQOL-39g shows good reliability and validity as a measure of health-related quality of life in people with stroke, including those with aphasia. An interview with the participant and the first author took place prior to the therapy study where the SAQOL-39 was used to collect the relevant information.
The participant completed ten (10) approximately 45-minute-long treatment sessions comprising of iTBS, immediately followed by RehaCom WM training over a span of 10 consecutive days, including weekends. Within each treatment session, approximately 15 minutes were devoted for setting up the participant with the TMS equipment and iTBS application, and 30 minutes were devoted to the RehaCom WM training task. The treatment regimen is depicted in Figure 3 below.
During the pretherapy baseline phase, the purpose was to establish the level of performance prior to treatment so that the effects of treatment on the task could be clearly measured. Seven outcome measures were used, and the information was collected three times, one week apart, prior to the therapy phase. Preceding the therapy phase, a T1-weighted MRI image was obtained of C. S.'s brain in order to accurately locate the target stimulation site using the Visor 2.0 neuronavigation system (ANT NEURO). Neuronavigated positioning of the stimulation coil allowed for repeated accuracy throughout the study.
(1) Transcranial Magnetic Stimulation (TMS) Equipment. Single-pulse TMS and intermittent theta-burst stimulation (iTBS) were delivered over the motor cortex and the left dorsolateral prefrontal cortex (LDLPFC), respectively, with the Magstim Rapid2 stimulator (Magstim Co., Wales, UK) connected to a 70 mm figure-8 air cooled coil. Biphasic TMS pulses were delivered with a posterior-to-anterior (P-A) current direction in both, single-pulse TMS and iTBS. The treatment intensity of TMS was individually adjusted the participant's resting motor threshold (RMT). RMT is the minimal intensity at which TMS of motor cortex produces a reliable motor evoked potential (MEP) of minimal amplitude in the target muscle. The MEP was determined with a surface electromyography (EMG) response in the 'target' muscle, through the placement of EMG leads over the first dorsal interosseous (FDI) muscle of the left hand. Full muscle relaxation was maintained through visual and online EMG monitoring. The coil was positioned at 45-degree rotation in relation to the parasagittal plane to induce P-A current in the underlying cortex. The motor "hotspot" was determined with a TMS intensity ranging from 45% to 50% of the maximum stimulator output, whereby single-pulse stimuli were delivered at varying positions across the scalp near the primary motor cortex (M1) while guided by a neuronavigation system (ANT NEURO) using each participant's recent anatomical MRI image. The motor "hotspot" was determined as the position on the scalp that yielded two consecutive MEPs with greater amplitude than the surrounding positions. The location within the left motor cortex that consistently elicited MEPs in the relaxed right FDI muscle was then defined as the motor hotspot. The coil was then placed over the defined target to obtain a MEP in the FDI of at least 50 muV in five or more of 10 consecutive stimulations of the left hand. For this study, a computerized adaptive parameter estimation through sequential testing (PEST) with the software TMS Motor Threshold Assessment Tool, MTAT 2.0, developed by Awiszus and Borckardt et al., was used to determine the RMT. The MTAT 2.0 freeware was obtained online (http://www.clinicalresearcher.org/software.html), and the option for assessment without prior information was selected. No other parameters were changed on the software.
(1) Transcranial Magnetic Stimulation: iTBS Application. The figure-8 coil was positioned tangentially to the skull, with the handle parallel to the sagittal axis pointing occipitally. The iTBS treatment consisted of bursts of three pulses at 50 Hz given every 200 milliseconds in two second trains, repeated every 10 seconds over 200 seconds for a total of 600 pulses. Based on the participant's recent MRI images, the Visor 2.0 neuronavigation suite (ANT-Neuro, Enschede, Netherlands) was used for image preprocessing, tissue segmentation, and registration into standard stereotaxic space. The stimulation target was defined in the left DLPFC by using the Talairach coordinates x = -39, y = 34, and z = 27. This technology enabled the reliable three-dimensionally precise reapplication of rTMS throughout the study. The participant received one session of iTBS each day for 10 consecutive days.
(2) RehaCom WM Training Equipment. Immediately following the iTBS session, the participant received 30 minutes WM training using the RehaCom Working Memory (WOME) software package (Hasomed GmbH, DE.). RehaCom WOME is a software package developed to train and improve WM performance. The WM training task involved card presentation in the form of a card game, using a complete card deck of 52 cards and consisting of different levels of difficulty. Three hierarchically ordered modules were designed to exercise the main components of WM on the basis of a card game: (a) storage systems, involving the maintenance of information; (b) selective attention, involving memorizing selective parts of information and inhibiting others; and (c) central executive/manipulation processes, involving active operating with the content retained in WM. RehaCom WOME training involves the memorization and manipulation of an increasing number of visually presented playing cards on a computer screen. Throughout the early levels of training, the participant is required to memorize a short series of cards and reproduce it in the same order, while at higher levels additional tasks are introduced to influence the memory process (e.g., memorize only the cards of a certain suit from a presentation of various cards). In total, there are 70 levels of difficulty. Feedback is constantly provided by the software, and the degree of difficulty is adapted based on the participant's performance level. The sessions were implemented in a quiet room, and C.S. responded on a Lenovo touchscreen laptop.
The Greek BDAE-SF
The RCPM
The MAIN
A Procedural Discourse task
A personal stroke narrative
The RehaCom Working Memory Screening Task
The Greek SAQOL-39
The posttherapy/follow-up phase consisted of two time points. The outcome measures were administered immediately after the completion of the last day of treatment (10th day) and at 3 months posttreatment at the follow-up stage. The purpose of immediate posttesting was to determine short-term efficacy and of the follow-up to determine long-term effects. The exact date of the follow-up was dependent on the participant's availability when contacted to set-up the appointment. The same battery of tools was used as with the baseline phase: | null | Not supported with pagination yet | null |
PMC6205929_01 | Male | 75 | A 75-year-old Caucasian male with a past medical history of coronary artery disease status post coronary artery bypass grafting 11 years prior, congestive heart failure with an ejection fraction of 25%, atrial fibrillation, hypertension, and hyperlipidemia presented to the hospital with dyspnea and chest pain. He has no history of tobacco use. He worked as a lawyer all his life and had no occupational exposures. On exam, the patient had diminished breath sounds over the left lung. Chest x-ray revealed a large left-sided pleural effusion (Fig. 1). Of note, he had previously been evaluated by his primary care doctor four months prior with similar symptoms and was found to have a left-sided pleural effusion. At that time, he underwent a thoracentesis at an outside facility with unknown pleural fluid analysis (PFA).
He was admitted to the hospital for further evaluation and underwent both a diagnostic and therapeutic thoracentesis (Fig. 2). PFA revealed a lymphocytic predominant, exudative effusion with total triglyceride level of 1406mg/dL consistent with a chylous effusion. Microbiology was negative. Cytology of the pleural fluid revealed reactive appearing mesothelial cells as evidenced by positive calretinin and Wilms tumor-1 (WT-1) immunohistochemical (IHC) stains. Adenocarcinoma was ruled out by negative BerEP4 and MOC-31 IHC stains (Fig. 3).
Computed tomography (CT) of the chest after the thoracentesis was performed revealing left lung airspace disease, pleural calcifications and mediastinal adenopathy (Fig. 4). Due to concern for a possible malignancy, he underwent an endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) biopsy of station 7 lymph node and transbronchial biopsy (TBBX) of the left lung infiltrate. Cytology of the EBUS-FNA lymph node specimen revealed abundant bland mesothelial cells with minimal amounts of lymphoid tissue. Interestingly, histologic examination of the concomitant TBBX specimen showed only rare atypical epithelioid cells floating within lymphatic spaces that stained with mesothelial markers. These findings were suspicious for a malignant process; however, limited sampling precluded a definitive diagnosis. A thoracoscopy was performed but an additional specimen could not be obtained due to extensive adhesions. A lymphangiogram was also performed. The contrast injected into the femoral vein did not progress to the level of the cisterna chyli suggesting an obstructive process in the lymph nodes. Due to concern for malignancy, the patient was offered a video-assisted thoracoscopic surgery, but he declined.
He returned to the hospital 3 months later with progressive dyspnea. CT chest revealed progression of the left lung infiltrate, a new right-sided pleural effusion and persistent mediastinal adenopathy (Fig. 5). Thoracentesis on the right sided revealed a chylothorax. He underwent another EBUS-FNA biopsy of station 7 lymph node and a TBBX of the left lung infiltrate. Cytologic examination of the lymph node FNA specimen again showed abundant bland mesothelial cells in the lymphatic spaces. Given the concern for MPM, the lymph node specimen was sent for additional ancillary testing - BRCA1 associated protein (BAP-1) IHC stain and CDKN2A/p16 homozygous deletion by fluorescent in situ hybridization (FISH). BAP-1 staining was lost in the mesothelial cells supporting MPM; the CDKN2A/p16 FISH study did not show a homozygous deletion. A third TBBX specimen of the left lung infiltrate was obtained which confirmed the diagnosis of MPM, epithelioid subtype.
Due to the patient's poor functional status, no treatment was offered. An indwelling pleural catheter was placed for palliative measures. Four months after his diagnosis, the patient presented with worsening dyspnea. He expired during that hospitalization. Autopsy examination demonstrated diffusely thickened pleura bilaterally, concentrated mostly of the left side, and measuring up to 1cm thick. Histologic sections confirmed the presence of dyscohesive malignant mesothelial cells, epithelioid subtype, with bland appearance throughout the pleura. The malignant mesothelial cells invaded the lung parenchyma minimally. While MPM is known to invade the lung parenchyma, in our case, tumor cells were present predominately within lymphatics in lung sections. Furthermore, metastatic tumor cells were evident in multiple mediastinal lymph nodes (Fig. 6). | bap-1, brca1 associated protein, chylothorax, chylous pleural effusion, ebus-fna, endobronchial ultrasound guided fine needle aspiration, epithelioid type, fish, fluorescent in situ hybridization, mpm, malignant pleural mesothelioma, malignant mesothelioma, pfa, pleural fluid analysis, reactive mesothelial cells, tbbx, transbronchial biopsy | On admission, computed tomography of the chest showed. left lung infiltrate, and. |
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PMC6205929_01 | Male | 75 | A 75-year-old Caucasian male with a past medical history of coronary artery disease status post coronary artery bypass grafting 11 years prior, congestive heart failure with an ejection fraction of 25%, atrial fibrillation, hypertension, and hyperlipidemia presented to the hospital with dyspnea and chest pain. He has no history of tobacco use. He worked as a lawyer all his life and had no occupational exposures. On exam, the patient had diminished breath sounds over the left lung. Chest x-ray revealed a large left-sided pleural effusion (Fig. 1). Of note, he had previously been evaluated by his primary care doctor four months prior with similar symptoms and was found to have a left-sided pleural effusion. At that time, he underwent a thoracentesis at an outside facility with unknown pleural fluid analysis (PFA).
He was admitted to the hospital for further evaluation and underwent both a diagnostic and therapeutic thoracentesis (Fig. 2). PFA revealed a lymphocytic predominant, exudative effusion with total triglyceride level of 1406mg/dL consistent with a chylous effusion. Microbiology was negative. Cytology of the pleural fluid revealed reactive appearing mesothelial cells as evidenced by positive calretinin and Wilms tumor-1 (WT-1) immunohistochemical (IHC) stains. Adenocarcinoma was ruled out by negative BerEP4 and MOC-31 IHC stains (Fig. 3).
Computed tomography (CT) of the chest after the thoracentesis was performed revealing left lung airspace disease, pleural calcifications and mediastinal adenopathy (Fig. 4). Due to concern for a possible malignancy, he underwent an endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) biopsy of station 7 lymph node and transbronchial biopsy (TBBX) of the left lung infiltrate. Cytology of the EBUS-FNA lymph node specimen revealed abundant bland mesothelial cells with minimal amounts of lymphoid tissue. Interestingly, histologic examination of the concomitant TBBX specimen showed only rare atypical epithelioid cells floating within lymphatic spaces that stained with mesothelial markers. These findings were suspicious for a malignant process; however, limited sampling precluded a definitive diagnosis. A thoracoscopy was performed but an additional specimen could not be obtained due to extensive adhesions. A lymphangiogram was also performed. The contrast injected into the femoral vein did not progress to the level of the cisterna chyli suggesting an obstructive process in the lymph nodes. Due to concern for malignancy, the patient was offered a video-assisted thoracoscopic surgery, but he declined.
He returned to the hospital 3 months later with progressive dyspnea. CT chest revealed progression of the left lung infiltrate, a new right-sided pleural effusion and persistent mediastinal adenopathy (Fig. 5). Thoracentesis on the right sided revealed a chylothorax. He underwent another EBUS-FNA biopsy of station 7 lymph node and a TBBX of the left lung infiltrate. Cytologic examination of the lymph node FNA specimen again showed abundant bland mesothelial cells in the lymphatic spaces. Given the concern for MPM, the lymph node specimen was sent for additional ancillary testing - BRCA1 associated protein (BAP-1) IHC stain and CDKN2A/p16 homozygous deletion by fluorescent in situ hybridization (FISH). BAP-1 staining was lost in the mesothelial cells supporting MPM; the CDKN2A/p16 FISH study did not show a homozygous deletion. A third TBBX specimen of the left lung infiltrate was obtained which confirmed the diagnosis of MPM, epithelioid subtype.
Due to the patient's poor functional status, no treatment was offered. An indwelling pleural catheter was placed for palliative measures. Four months after his diagnosis, the patient presented with worsening dyspnea. He expired during that hospitalization. Autopsy examination demonstrated diffusely thickened pleura bilaterally, concentrated mostly of the left side, and measuring up to 1cm thick. Histologic sections confirmed the presence of dyscohesive malignant mesothelial cells, epithelioid subtype, with bland appearance throughout the pleura. The malignant mesothelial cells invaded the lung parenchyma minimally. While MPM is known to invade the lung parenchyma, in our case, tumor cells were present predominately within lymphatics in lung sections. Furthermore, metastatic tumor cells were evident in multiple mediastinal lymph nodes (Fig. 6). | bap-1, brca1 associated protein, chylothorax, chylous pleural effusion, ebus-fna, endobronchial ultrasound guided fine needle aspiration, epithelioid type, fish, fluorescent in situ hybridization, mpm, malignant pleural mesothelioma, malignant mesothelioma, pfa, pleural fluid analysis, reactive mesothelial cells, tbbx, transbronchial biopsy | Computed tomography of the chest 3 months after initial admission showed worsening left lung infiltrate and a new right sided pleural effusion. Lung window settings: thickness 1mm, width 1600. |
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PMC4531766_01 | Male | 43 | A 43-year-old man was admitted to our hospital with one-month history of productive cough. He had a 3-year history of mitral stenosis and an operation for mitral valve replacement. There was no history of recurrent infection or other evidence of immunodeficiency. Physical examination revealed a temperature of 36.8 C. Chest examination revealed an inspiratory crackle in the right lower lung field. Laboratory tests revealed a leukocyte count of 11,600/muL and hemoglobin of 13.2 g/dL. Differential cell count disclosed the following values: neutrophils 76%; lymphocytes 17%; monocytes 5%; eosinophils 1.7%; basophils 0.3%. Chest radiograph showed focal consolidation of the right lower lobe (Figure 1). Computed tomography of the chest demonstrated patchy air-space consolidation and atelectasis of the right lower lobe (Figure 2). Gram stain showed many Gram positive cocci; AFB smear and culture for Mycobacterium tuberculosis were negative; there were no fungi. Fiberoptic bronchoscopy showed subtotal occlusion of the right superior segment of the lower lobe by a yellow-white, stony-hard mass, which was surrounded by inflamed and edematous bronchial mucosa (Figure 3). Histologically, the biopsy specimen revealed an inflammatory cellullar infiltration and colonies which were formed of a radiating network of filaments staining intensely with hematoxylin (Figure 4). The Gram stain also showed a thin, filamentous, Gram-positive, branching organism. (Figure 5). The patient was initially treated with 10 million units of intravenous penicillin daily for two weeks, followed by oral amoxacillin/clavulanic acid. After 3 months of therapy, the clinical manifestations and radiologic findings were markedly improved (Figure 6). | null | Computed tomography of the chest shows patchy air-space consolidation and atelectasis of the right lower lobe. |
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PMC3929864_01 | Male | 4 | A four-year-old boy was diagnosed with acute lymphoblastic leukemia in February 2011. Thereafter, he received a scheduled chemotherapy plan of 2 - 2.5 years. After cycles of chemotherapy, he received erythrocytes, platelets and fresh blood, due to chemotherapy-induced cytopenia. In early August, the boy complained of anorexia, nausea, and fatigue. Elevated levels of transaminases were detected in his serum. Serological tests for hepatitis A, B, C, and CMV had negative findings, whereas anti-HEV IgM was found to have positive results (Table 1). At admission on the 8th October, his serum values were as follows; alanine aminotransferase (ALT) 540 U/L (normal: < 45), aspartate aminotransferase (AST) 259 U/L (normal: < 50), total bilirubinemia (TBIL) 27.6mumol/L (normal: < 17.5 mumol/L), alkaline phosphatase (ALP) 157 U/L (normal: 45 - 135), c-glutamyltransferase (GGT) 97 U/L (normal: 10 - 47). Anti-HEV IgM anti-HEV IgG had positive results, but both were at low levels in terms of the ELSIA OD values of 0.27 and 0.22, respectively. HEV RNA was detected in the serum using RT-nested PCR. The HEV genotype was determined to be 4d by sequencing and analyzing the PCR amplicon (GenBank accession number: KF691589) (Figure 1). Physical examination at diagnosis of the HEV infection had normal findings, no jaundice or hepatosplenomegaly was observed. Color Doppler Ultrasound showed that the liver was normal in size and structure. However, when the patient insisted on leaving on November 10th for the following scheduled chemotherapy, HEV RNA in the serum had negative results, but the transaminases did not normalize; ALT 118 U/L, AST 94U/L, ACP 190 U/L, GGT 97 U/L.
In May 2013, twenty months later, the patient returned to our hospital for the treatment of hepatitis, after completing the latest intensive chemotherapy. Pathological values were obtained as follows; ALT 523 U/L, AST 822 U/L, ALP 527 U/L, GGT 352 U/L,serum albumin (ALB) 36.2 g/L (normal: 37-53 g/L), and TBIL 29.7 mumol/L. Anti-HEV IgM and IgG had positive results in the serum, and HEV RNA was also positive, with high levels up to 3.6 x 106 Geq/mL. The liver was still normal in size and structure by Color Doppler Ultrasound detection. The sequence of the 304 bp amplicon in the HEV ORF2 region was identical to that of the isolate obtained in 2011. It was most likely as a persistent HEV infection. Two months later, the HEV RNA levels had decreased in the serum to below detection limits, while the ALT level was still out of the normal range and anti-HEV IgM remained positive (Table 1). | chronic hepatitis, hepatitis e virus, persistent infection, precursor cell lymphoblastic leukemia-lymphoma | Not supported with pagination yet | null |
PMC9590347_01 | Unknown | 49 | Indonesia has the third-highest prevalence of tuberculosis (TB) after India and China. In Indonesia, pulmonary TB is the second-highest cause of mortality among infectious diseases. Three-quarters of the TB prevalence in Indonesia is among those aged between 14 to 49 years old. Osteoarticular TB is an uncommon form of extrapulmonary TB (EPTB); it comprises 1-6% of all TB cases and 10-15% of all EPTB cases. The most frequent sites of osteoarticular TB infection are the spine, hip, and knee.
Osteoarticular TB diagnosis is often delayed. Diagnostic delayed means that there is time interval between onset of symptoms and confirmation of TB to the patients. The cut-off point was 1 months (4 weeks). EPTB results from the hematogenous and lymphatic spread of M. tb bacilli. Tuberculous osteomyelitis and arthritis generally arise due to the reactivation of bacilli lodged in the bone during the original primary infection. The predilection of the bacillus for large joints is due to the rich vascular supply in the growth plates of the long bones. Tuberculous arthritis is believed to result from the extension of the initial infection of the bone to the joint. In the Netherlands and England, concomitant pulmonary TB has been reported in 29% and 15% of osteoarticular TB patients, respectively. In Karachi, Ali et al reported concurrent pulmonary TB in nearly 50% of osteoarticular TB cases. However, only 6.9% of 5337 osteoarticular TB cases had concurrent pulmonary TB. Similarly, a study performed in Turkey and Denmark also found low rates of concomitant pulmonary TB in osteoarticular TB cases. Despite its prevalence in other countries, osteoarticular TB is still underdiagnosed in Indonesia.
In this study, 30 osteoarticular TB cases from two government hospitals in Jakarta, Indonesia, were retrospectively analyzed. This study aims to provide clinical and radiologic-histopathologic descriptions of delayed osteoarticular TB, its management, and outcomes. | jakarta, caseous necrosis, extrapulmonary tb, osteoarticular tb, tuberculosis | Not supported with pagination yet | null |
PMC3747382_01 | Male | 44 | A 44-year-old right-handed male, with previously healthy status and no family history, was admitted with complaints of acute, generalized headache associated with left arm and leg weakness. He had been suffering from oral aphthous ulcers for 5 years but no genital ulcers. One year ago, he was diagnosed with a cerebral ischemic stroke reveled with left hemiparesis. He developed significant behavioral changes, insomnia, and visual hallucinations that occurred 2 weeks prior to the outbreak of right hemiparesis. The patient was afebrile. He had a blood pressure of 130/80 mmHg, a pulse of 84 beats/min and a respiratory rate of 18 breaths/min. Physical examination revealed also oral aphthous ulceration but no genital scars due to healed ulcers. A thorough neurological examination revealed a normal conscience, no neck stiffness, but dysarthria, quadripyramidal syndrome with tetraparesis, predominant left motor deficit, and bilateral Babinski sign. Examination of the sensibility showed decreased senses of touch, pain, and temperature in the left side of the body. Computed tomography imaging and cerebral MRI disclosed an ancient ischemic right capsulolenticular lesion, with recent ischemic lesions in left capsule-lenticular region (Figure 1). MRI with gadolinium revealed enhancing lesions compatible with intracranial multiple arterial aneurysms (Figure 2). Thoracoabdominal computed tomography angiography had showed no extracranial aneurysms. Laboratory analysis showed a white blood cells count at 9.000 cells/mL with 85% neutrophils, a hemoglobin value at 10.8 g/dL, and a platelet count at 570.000 cells/mL. The erythrocyte sedimentation rate was over 111 mm/hour and the C-reactive protein was at 30 mg/L. Creatinine, electrolyte levels, liver tests, and coagulation studies were within the normal range. All serologic markers of hepatitis B and C, HIV, and syphilis were negative and no microorganisms could be identified from his blood and urine cultures. Immunological analysis including anti-nuclear and anti-phospholipid antibodies, rheumatoid factor, and anti-neutrophilic cytoplasmic antibodies were also within the referential range. Multiple laboratory tests and radiological studies ruled out a hypercoagulability syndrome and a heart disease. A Pathergy test was repeated and found to be clearly negative. The diagnosis of BD was made based on the presence of recurrent oral aphthous ulcers and positive human leukocyte antigen (HLA) B51 in the absence of evidence of other diseases.
Since then, the patient was treated with Methylprednisolone pulses linked with a high-dose regimen of prednisone (1 mg/kg/day) during two months, daily Azathioprine, and physical rehabilitation was started. Coil embolization of aneurysms was not performed because the aneurysms were numerous and there was no bleeding.
Ten months after discharge, despite marked regression of mental impairment and no further ischemic events, he developed a pseudobulbar effect including uncontrollable episodes of crying, dysarthria associated with urinary incontinence. The control MRI remained unchanged with persistent diffuse and unruptured aneurysmal dilatation and ancient cerebral stroke (Figure 3). | null | Not supported with pagination yet | null |
PMC9922525_01 | Female | 70 | A 70-year-old female was brought to the emergency medicine department by her son with a history of altered sensorium for three days. On presentation, her airway was patent with 70% saturation on room air, and air entry was absent on the right lower lobe on auscultation. Her pulse was at 75/minute and 70 mm hg of blood pressure with raised jugular venous pressure (JVP). She was drowsy but followed commands with Glasgow Coma Scale (GCS) E3, V5, and M6. Her blood sugar level was 120 mg/dl. Babinski's sign was negative, deep tendon reflexes were diminished, and neck stiffness and rigidity were absent on examination. Her extremities were cold, with a body temperature of 35.5 C. On local examination, the patient was pale with facial puffiness, as shown in (Figures 1, 2)
Her abdomen was distended, there was a dull note on percussion, and bowel sounds were sluggish on auscultation. Propped-up position oxygen was started via Hudson mask at a rate of 14 lit /minute, and 12 lead ECG was done as shown in (Figure 3).
Arterial Blood Gas (ABG) was done, which was suggestive of uncompensated respiratory acidosis, which gets improved after management initiation as shown in (Table 1).
There was a history of deep vein thrombosis of the left lower limb ten years back. The swelling persisted in the bilateral lower limb for ten years, and the patient was not on any treatment. She had no history of hypertension, diabetes mellitus, bronchial asthma, tuberculosis, hypothyroidism, seizures, or loss of consciousness. Blood samples were withdrawn for Complete blood count, liver function test, renal function test, D-DIMER, TSH, free T3, and free T4. Results are shown in Table 2. Figure 4 depicts the chest x-ray anterior-posterior (AP) view. CT brain plain was normal.
The patient was started on Inj Levothyroxine 20 mcg IV bolus and Inj Pantoprazole 40 MG IV. Inj unfractionated Heparin 5000 IU IV was given for pulmonary thromboembolism. Inj Piperacillin and Tazobactam 2.25 GM IV was given.The patient was shifted to the medical intensive care unit (MICU) for further management. After 12 hours, the patient was conscious and oriented to time, place, and person with GCS 15/15 and maintained a blood pressure (BP) of 100/60 mm Hg. | cold intolerance, constipation, fatigue, hypothyroidism, myxedema crisis, weight gain | Not supported with pagination yet | null |
PMC8294269_01 | Male | 61 | Here, we report a case of a probable reactivation of SARS-CoV-2 in an immunosuppressed patient who previously had COVID-19 and who had received one dose of COVID-19 mRNA vaccination (BNT162b2, BioNTech/Pfizer). A 61-year-old male suffering from acute myeloid leukemia (AML) was admitted to our center for a planned allogeneic hematopoietic stem cell transplantation (allo-HSCT). AML was diagnosed in March 2020. The patient received no intensive induction chemotherapy because of coronary heart disease as comorbidity. The patient received 11 cycles of the hypomethylating agent decitabine combined with the BCL2-inhibitor venetoclax until February 2021. The AML was morphological in complete remission but with molecular persistence of NPM1. Thus, allo-HSCT was planned. In February 2021, the patient had received the first dose of a COVID-19 mRNA vaccine (BNT162b2, BioNTech/Pfizer). Two weeks later, when the beginning of the 12th cycle of chemotherapy was planned, he had presented to another center with myalgia, fever, and gastro-intestinal symptoms, without respiratory symptoms. A naso-oropharyngeal swab was tested SARS-CoV-2 positive by PCR (Table 1). During his stay, the patient did not develop any significant respiratory symptoms and did not require oxygen supplementation. CT scan showed subpleural ground glass infiltration compatible with COVID-19 pneumonia with a very limited extension. He was treated with symptomatic therapy and standard antithrombotic prophylaxis. The clinical course was favorable and the patient was discharged after 11 days. Two following naso-oropharyngeal swabs, performed 7 and 10 days after diagnosis, respectively, were negative. At the same time, anti-SARS-CoV-2 IgG with a high titer of 743 AU/ml was detected; IgM was equivocal. Since the patient had developed the infection 2 weeks after receiving the first dose of the vaccine and since SARS-CoV-2 IgG antibodies were already positive, we decided not to administer the second dose of the COVID-19 vaccine, assuming that the patient would acquire natural immunity after the infection. Due to the good general condition of the patient and the molecular leukemia persistence, we decided to proceed to allo-HSCT without any delay. On admission at our center, the patient was asymptomatic and physical examination was normal. Laboratory tests showed mild anemia and thrombocytopenia with normal CRP and without signs of a coagulopathy. The AML was in morphological complete remission prior to allo-HSCT. A CT showed no residual signs for pulmonary infection. SARS-CoV-2 was undetectable in the naso-oropharyngeal swab. We started the planned conditioning regimen with fludarabine, cyclophosphamide, and 2-Gy total body irradiation (TBI) which was well-tolerated. The GvHD prophylaxis consisted of high-dose cyclophosphamide post-transplant, tacrolimus, and mycophenolate mofetil. The stem cell source was bone marrow from his haplo-identical son. A few days after starting conditioning, the patient developed lymphopenia (Table 1) in addition to the already known anemia and thrombocytopenia. A new, routinely performed SARS-CoV-2 saliva PCR on day -4 before HSCT came out to be positive, with a semi-quantitative CT value of 35.9 (cycle threshold). The antibody testing was repeated, showing 136 U/ml anti-SARS-CoV-2 spike antibodies (normal range < 0.7 U/ml) and 31.9 U/ml anti-SARS-CoV-2 nucleocapsid-antibodies (normal range <= 1 COI). The antibody testing was performed with the electro-chemiluminescence immunoassay (ECLIA) method. The patient was afebrile and asymptomatic and the inflammation markers were normal. We continued the conditioning chemotherapy. Since a worsening of the immune situation was expected, we administered one unit of convalescent plasma. A confirmatory naso-pharyngeal swab PCR tested SARS-CoV-2 positive. The quantitative viral load was however below the limit of detection (< 1000 copies/ml). Two days later, a monitoring SARS-CoV-2 quantitative PCR test showed again a viral load of <1000 copies/ml and the isolation was ended according to the internal guidelines. In addition, the following SARS-CoV-2 quantitative PCR tests showed viral loads of < 1000 copies/ml (Table 1). The neutrophil engraftment (> 0.5 G/l) occurred on day +23 and the patient discharged on day +31. Lymphopenia persisted until discharge (0.02 G/l). Two months after allo-HSCT, the patient is still in complete molecular remission (NPM1A negative in peripheral blood and bone marrow) without signs of acute graft-versus-host disease. | acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, covid-19, sars-cov-2 | Not supported with pagination yet | null |
PMC4314908_01 | Male | 13 | A 13-year-old Asian, boy, from urban area of East India, with normal birth and developmental history, past history of febrile convulsions till the age of 6 years, medical history of bronchial asthma and ankyloglossia, family history of single manic episode in father and dissociative convulsions in mother, presented in November 2003 to the Outpatient Department (OPD) of Centre for Child and Adolescent Psychiatry, Central Institute of Psychiatry, Ranchi, India with reduced interest in studies, episodes of sudden unarousable "sleep," lasting as long as 14-16 h and sudden awakening for 2 weeks. Simultaneously, there are periods of unresponsiveness for 16-18 h starting and ending abruptly with no response to noxious stimuli and complete amnesia. An initial impression of hypersomnia unspecified with a possibility of dissociative disorder was made, and he was admitted for investigation and management. He was responsive to behavioral management comprising of the problem behavior extinction and differential reinforcement of alternative behavior. Fluoxetine was started as he was noted to be sad and disinterested.
Pentothal interview was unremarkable, and Video electroencephalogram with quantitative analysis during apparent period of unresponsiveness showed no sleep changes or abnormal focal or generalized discharges. Polysomnography was also unremarkable except for increased rapid eye movement latency and relatively increased percentage of Stage 3 and 4 sleep in total sleep time. Mental status did not reveal any depressive cognition. With the above regimen, he showed good response and a diagnosis of dissociative disorder unspecified was kept at discharge. He came for regular follow-up till 1 year, but thereafter did not report till 3 years, a period in which he had stopped his medicines, maintaining well. He reported again in November 2007 with a 3 months history of low mood, irritability, poor concentration, difficulty in studying and two suicidal attempts. He was admitted with a diagnosis of severe depressive episode without psychotic symptoms. Fluoxetine was increased to 40 mg but he developed significant deterioration with hyperactivity, decreased need for sleep, anger outbursts and grandiose claims. An impression of antidepressant-induced manic switch was made and he was put on electroconvulsive therapy as he also expressed significant suicidal ideations and attempted once in the ward to hang himself during the course. With this he had good response and after 8 sessions he was put on lamotrigine considering family history of mania, high impulsivity, and age of onset, and it was increased up to 200 mg/day on which he attained remission over 4 weeks and was discharged from hospital.
This can be observed as an absorbing case considering the way the clinical presentation evolved over a period of 5 years. To the best of our knowledge, there is no similar presentation and evolution of psychopathology in children and adolescents. There were genetic vulnerabilities to both bipolarity and dissociative disorder, which may have been exposed to an examination failure stress and brought about the symptoms in the child. Draijer and Langeland have noted that severity of dissociation could be predicted by maternal dysfunction; in our case we could speculate that the maternal dissociation was a response to escape some overwhelming stress and the patient having witnessed these attacks took a similar route to escape his stressor.
About the periods of unresponsiveness and "sleep" noted in our patient, it has been noted by Putnam et al. that the young patients may recurrently cycle through sleep and drowsy states more than the older population. Our subject had displayed symptoms of depression in the first episode of illness itself- as per Hornstein and Putnam there may be a number of clusters within which dissociative behavior can overlap with a number of internalizing disorders like depression, anxiety etc. This patient demonstrated gradual response to psychotherapeutic interventions, although a pentothal interview interestingly revealed the persistence of amnesia for the month in which he did not pass his examinations, a psychological and social stressor as per Srinath et al., who noted academic pressures to be an important underpinning among Indian children attending psychiatric OPD with features suggestive of "hysteria." The switch induced by the antidepressant added yet another facet to the case as there have been observations of selective serotonin reuptake inhibitor-induced hypomanic switch in patients of dissociative disorder.
There have been proposed hypotheses of dissociative identity disorders (DIDs) and bipolar disorder as been lying on a continuum based on the phasic alterations of the DID patient's personalities and the bipolar subject's affective changes. On a similar note, our subject's longitudinal course of illness gave an opportunity to observe the evolution of this process. Thus, our patient was a candidate who fell into the bipolar spectrum constellation with age of onset added to his predisposing factors. In a Norwegian sample, it was noted that there is a significantly higher prevalence of dissociative symptoms in bipolar II subjects when compared to MDD patients. Long-term outcome and prognosis of dissociative disorder with onset in childhood or adolescence in a large German sample revealed that more than 50% of the patients went on to develop anxiety or somatoform disorder over a clinical course of around 10 years but mood disorder was not reported. This makes a strong point toward the possible common lineage between these two groups of disorders and may raise a theoretical possibility of dissociation being a forerunner to bipolarity in clinical populations and thus helping clinicians' pickup occult bipolarity in dissociative disorders and instituting early treatment. Further research in the coming years may help shed light on this interesting probability. | null | Not supported with pagination yet | null |
PMC9932662_01 | Female | 25 | A 25-year-old woman was brought to our psychiatric clinic for severe PTSD and depression with suicidal ideation. Her depressive symptoms developed at the age of 20 after she was verbally abused by a teacher and failed an important project. In addition to a depressed mood, she experienced a loss of interest, feelings of worthlessness, psychomotor retardation, and suicidal ideations. Her family brought her to a psychiatric clinic, where major depressive disorder (MDD) was diagnosed. She began taking escitalopram (10 mg/d increasing to 20 mg/d in 1 month) and receiving psychotherapy. Her symptoms of MDD gradually improved later and she could graduate from college on schedule.
However, in August 2020, she experienced unexpected verbal violence and threats from a colleague at her place of work. Her colleague often consumed alcohol, slammed doors, and swore at her, which caused her to feel stressed. She developed hyperarousal, re-experience (flashbacks and nightmares), avoidance (avoiding the office and her colleague), and transient auditory hallucinations (an unknown voice criticizing her), which persisted for more than a month. She then experienced a relapse of depression with suicidal ideation. PTSD and major depressive disorder were diagnosed according to the diagnostic and statistical manual of mental disorders-5 (DSM-5) criteria. Medications including escitalopram 20 mg per day (4 weeks), duloxetine 60 mg per day (4 weeks), venlafaxine 150 mg per day (4 weeks), and a combination of 60 mg duloxetine and 5 mg aripiprazole daily (4 weeks) were subsequentially used. She also received psychotherapy for 4 weeks. However, she did not respond well to these medications and suffered from the drug side effects including dizziness, nausea, and weight gain. She refused additional antidepressant treatment and kept venlafaxine 150 mg per day. Therefore, she was referred to our brain stimulation center for an rTMS consultation. Her family has no history of MDD or PTSD.
We used the Davidson Trauma Scale (DTS) to evaluate the severity of her PTSD. The DTS yields a frequency score (ranging from 0 to 68). The Beck Depression Inventory (BDI) was used to evaluate the severity of her depression. The Beck Anxiety Inventory (BAI) was used to measure the severity of her anxiety symptoms. The BDI and BAI yields a frequency score (both ranging from 0 to 63). The severity of PTSD, depression, and anxiety increases with the scores. Higher scores mean worse PTSD, depression, and anxiety. She scored 62, 52, and 34 points on the DTS, BDI, and BAI, respectively.
After the patient provided signed informed consent, we adopted a new rTMS treatment, theta-burst stimulation (TBS), of the bilateral DLPFC with an Apollo TMS Therapy stimulator (MAG and More, Munich, Germany) equipped with a figure-of-eight coil. First, we applied cTBS with 20 trains of 10 bursts (short bursts of 3 stimuli at 50 Hz, repeated at 5 Hz), with 600 pulses for 40 s at 80% RMT, targeting the right DLPFC. Second, we applied iTBS with 20 trains of 10 bursts (short bursts of 3 stimuli at 50 Hz, repeated at 5 Hz) given at 8 s intervals at 600 pulses for 200 s at 80% RMT, targeting the left DLPFC. After a 20-min intersessional rest period, we performed a second round of iTBS for 200 s, targeting the left DLPFC. Our design consists of 3 sessions, first two (cTBC, iTBS) being sequential and then with 20 min break before the 2nd iTBS session. The patient received 1,800 pulses in each treatment and total 18,000 pulses in the whole treatment course. The coil localization was based on the algorithm developed by Beam et al.. The Beam-F4 position was used for the right DLPFC and the Beam-F3 position was used for the left DLPFC. Because of her daily work and the COVID-19 pandemic, she cannot visit our department every day. The subsequent stimulation sessions were performed two to three times per week. We completed a total of 10-day (30 sessions) within 4 weeks (Figure 1).
The patient's PTSD and depressive symptoms gradually improved. After TBS treatment course, her symptoms improved (scores of 42, 7, and 4 on the DTS, BDI, and BAI, respectively) (Table 1). For the DTS scale assessment, symptom item 14 (increased irritability) and 15 (concentration difficulties) improved the most, from 4 to 1. The side effects of the treatment, such as dizziness or headache, were transient and disappeared after the TBS treatment finished. | depression, dorsolateral prefrontal cortex, post-traumatic stress disorder, theta-burst stimulation, transcranial magnetic stimulation | Not supported with pagination yet | null |
PMC8024077_01 | Male | 20 | A 20-year-old male presented to the emergency department complaining of gradually increasing noncolicky pain right side abdomen with multiple episodes of nonprojectile vomiting, obstipation, and progressive abdominal distension for the past 3 days. There was fever with chills and rigor for a similar duration. There was no past history of chronic constipation. There was no personal or family history of tuberculosis. At the time of presentation, the patient was having a pulse rate of 110 beats/minute, a blood pressure of 120/82 mm Hg, and a temperature of 39.5 Celsius. During the abdominal examination, there was tenderness and guarding over the right side of the abdomen with signs of inflammation on the right side back. There was no associated inguinal hernia. On auscultation, bowel sounds were sluggish.
Blood investigations revealed haemoglobin of 11 gm/dL, white cell count of 10,900/cumm with 80% polymorphs, 16% lymphocytes, 2% monocytes, and 2% eosinophil. Liver function test, renal function test, serum electrolyte, serum glucose, and urine analysis were all normal. Typhi antigen card test was negative.
Abdominal X-ray in the erect position showed the right side minimal pleural effusions with dilated loops of the small bowel. Ultrasonography (USG) of the abdomen reported multiple fluid distended intestinal loops suspecting paralytic ileus/subacute intestinal obstruction. The patient was kept on conservative treatment with Ryle's tube suction, intravenous fluids, and parenteral antibiotics. By the 4th day of conservative treatment, the patient started passing flatus and feces and was gradually shifted to a liquid diet.
On the 8th day of admission, the patient complained of painful swelling right scrotum. Scrotal examination showed signs of inflammation with fluctuation on the right side. CT scan of the abdomen showed discontinuity in the posterior wall of ascending colon with a large retroperitoneal collection having multiple internal air lucencies, displacing ascending colon and caecum medically. The right retroperitoneal collection extending superiorly from right pararenal and posterior perihepatic soft tissue planes to the right iliac fossa and right thigh (Figure 1).
Around 350 ml of fecal contents was evacuated by incision & drainage (I&D). The fecal discharge gradually started decreasing while the patient was continued on a liquid diet (Figure 2). The cellulitis of the right side back was also started decreasing. On the 26th day of admission, the patient was discharged in satisfactory condition with no discharge from the scrotal wound. 4-year follow-up was uneventful. | null | Not supported with pagination yet | null |
PMC3544255_01 | Male | 61 | A 61-year-old man presented to our department with symptoms of gross hematuria and intermittent right pelvic pain. He had a past medical history of arterial hypertension, psoriasis, an annealed lung Tbc, and a smoking history of 60 pack years. Urine analysis showed microscopic hematuria. Biochemical data were within normal limits. Ultrasound and cystoscopy were normal. Intravenous urography (IVU) demonstrated a tubular filling defect with partial obstruction of the right mid ureter. Retrograde ureteropyelography confirmed a 5 cm long tubular mass in the mid ureter proximal to the iliac vessels (Figure 1). Further investigation was done by flexible ureteroscopy showing a pediculated tumor of the ureter with a vulnerable surface (Figure 2). Urine cytology and biopsy of the tumor and the renal pelvis were taken. A pigtail catheter was inserted. Results of urine cytology and the biopsy were negative for malignancy. A staging CT scan was performed which showed a nonspecific slight dilatation of the right renal pelvis and a small thickening of the right ureter without evidence of metastasis or lymphadenopathy (Figure 3). Open exploration of the right ureter was performed by a Gibson incision. After palpating the mass above the level of the iliac vessels, an ureterotomy was made. The tumor presented with a small thin basis and a length of 5 cm. Intraoperative frozen section revealed a benign fibroepithelial polyp (UFP) without evidence of malignancy (Figure 4). Segment resection of the ureter was performed followed by a tension-free spatulated end-to-end anastomosis. The patient was discharged from hospital three days postoperatively with a foley catheter in place, which was removed at day 10. The pigtail catheter was removed 5 weeks later. | null | Not supported with pagination yet | null |
PMC5824895_02 | Female | 27 | A 27-year-old woman was diagnosed with ileocolonic nonstricturing, nonpenetrating Crohn's disease at the age of 17 years. Other comorbidities included osteopenia, previous erythema nodosum, sinusitis, and a positive lupus anticoagulant result. Her family history included autoimmune hemolytic anemia, GPA, and tuberculosis. In the 4 years following diagnosis, her Crohn's disease followed a steroid-refractory course complicated by stricturing of the large intestine, leading to a segmental transverse colon resection and right-sided double-barrelled colostomy. After 1 year, she underwent a loop ileostomy for a perforated internal hernia. In the subsequent 5 years, additional surgeries were also performed for reversal of the loop ileostomy and subsequent refashioning of the colostomy. Her treatments included several courses of corticosteroids, azathioprine (developed intolerance), infliximab (anaphylaxis), and later adalimumab with addition of methotrexate. While off adalimumab for 1 week (recurrent viral infections), she presented with a 2-day history of acute onset of bilateral painful S-shaped periorbital swelling, moderate erythema, and chemosis worse on the left with diplopia (Figure 2A). Ocular movements were restricted and episcleritis was evident. A CT scan of head, orbits, and sinuses revealed bilateral lacrimal gland enlargement. Lateral and superior recti were also enlarged (Figure 1E to F). Blood analysis showed raised inflammatory markers with a WCC of 21.6 x 109/L and a CRP of 166 mg/L, normal serum angiotensin-converting enzyme (ACE) levels, and thyroid function. Immunologic tests showed positive perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) and low proteinase 3 (PR3). Neither pulmonary nor renal involvement was present. Postoperative appearances are shown in Figure 2B. Histology showed a chronic dacryoadenitis, acute vasculitis of medium-sized vessels, and necrotizing histiocytic granulomas (Figure 3B). Stains for periodic acid-Schiff-diastase, Ziehl-Neelsen, and IgG4 were negative, and pus collected from the lacrimal gland during the biopsy did not reveal any microbial growth. The patient was started on a 2-day course of intravenous Co-amoxiclav (1.2 g 3 times daily) and an 8-week reducing course of high-dose oral prednisolone (commencing at 60 mg daily) for presumed OID complicating Crohn's disease. Following recommencement of weekly 25 mg subcutaneous methotrexate and biweekly adalimumab, her symptoms and signs had completely resolved at ophthalmological assessment 1 week later (Figure 2C). | orbital inflammation, inflammatory bowel disease | Not supported with pagination yet | null |
PMC6145047_05 | Female | 43 | The sister (II-3) of the proband is a 43-year-old normotensive Caucasian female (height 170 cm, weight 57 Kg) with severe scoliosis and osteoporosis. She presented normal aortic root (31 mm; Z-score 0.23) and ascending aorta (25 mm).
BAV was present only in the proband out of the 5 family members evaluated. In history taking of each member of the family there was no evidence of either occurrence of BAV or aortic surgery or sudden death.
NGS targeted approach identified in the proband (II-1) 5 rare heterozygous variants [minor allele frequency (MAF)<0.01] (Table 1) in 4 different genes: FBN1 (p.Asn542Ser and p.Lys2460Arg), NOTCH1 (p.Val1739Met), LTBP1 (p.Arg1330Gln), and TGFBR3 (p.Arg423Trp) (Figure 1). These variants were confirmed through Sanger technology (Figure 2).
Characteristics of identified variants and results from in silico prediction of the pathogenetic effect were reported in Table 1. Variants detected in the proband were also investigated in his first-degree relatives (Figure 1). NOTCH1 and LTBP1 mutations were present in proband's mother (I-1) and brother (II-2). Concerning FBN1 gene, both p.Asn542Ser and p.Lys2460Arg variants were inherited in cis by the mother (I-1) and not found in any of other family members. Finally, the TGFBR3 variant was transmitted by the father to the offspring (Figure 1).
In the proband, we also identified 139 common genetic variants (39 nonsynonymous) in the coding regions (data available if required). | null | Not supported with pagination yet | null |
PMC2700580_01 | Female | 30 | A 30-year-old female presented to the emergency department of the hospital with diffuse headache and bilateral proptosis, which was associated with vomiting. There was no ear discharge, cough, or burning micturition. There was no history of trauma, or seizures. She had no past history of convulsions or tuberculosis. She had no history of sickle cell disease, hypertension, and diabetes. She was P2L2A0 and the previous deliveries were normal without any complicating events.
On examination, she was conscious, but drowsy with low-grade fever.glasgow coma scale was 9 at the time of admission. She was pale and anicteric. Her pulse was 120/min and regular. Her blood pressure on admission was 130/90 mmHg in left upper limb supine position. Main neurological finding was left third nerve palsy with papilloedema.
Local examination of eyes showed bilateral proptosis which was associated with chemosis and corneal haziness. Other systemic examination was unremarkable. Her hemoglobin was 8.5 gm/dl, hematocrit was 26%, total leukocyte counts were 15,000 per cubic mm. Blood culture was sterile. Platelets were normal. There was no sickle cell on peripheral smear. There was no deficiency of protein C or S. Antiphospholipids antibody was normal. Her chest film was normal. Patient underwent plain and post-contrast computed tomography (CT) head scan which showed bilateral superior ophthalmic vein thrombosis extending to the thrombosed cavernous sinus [Figure 1]. There was also right subdural hematoma (appears to be chronic) with midline shift [Figure 2]. There was no sign of cerebritis (heterogeneous enhancing area in adjoining hypodense area) in adjacent cerebral parenchyma, so chances of empyema were less likely. On the basis of this CT scan findings and clinical feature, we treated the patients with higher antibiotics in the form of combination of sulbactum and ceftrixone intravenously twice a day and corticosteroids. Heparin was started in view of high-risk benefit ratio of cavernous sinus thrombosis and subdural hematoma. Neurosurgical consultation was also taken, hematoma (there were no evidence of pus) was evacuated. In spite of all, patient did not show any improvement and died subsequently. We did not send her for autopsy due to resistance by her relatives. | cavernous sinus thrombosis, chronic, subdural hematoma | Not supported with pagination yet | null |
PMC6859015_02 | Female | 69 | A 69-year-old Tunisian female was admitted in 2005 for arthritis and fever. The examination revealed a temperature of 39.7 C, an evanescent diffuse maculopapular rash and symmetrical polyarthritis involving knees, wrists and metacarpophalangeal joints. There was neither lymphadenopathy nor hepatosplenomegaly. Laboratory evaluation revealed: Hb: 74g/l, a white blood cell count of 17.6x109/l (neutrophils: 89%) platelets: 471x109/l, erythrocyte sedimentation rate of 145mm/h and C-reactive protein: 440mg/l. The liver function test scores were elevated: AST: 56 IU/l, ALT: 53IU/l (normal value: 10 to 40IU/l), GGT: 124IU/l (normal value: 10-35IU/l). The serum ferritin was elevated: 3000ng/ml (normal value: 11 to 250ng/ml). Urinalysis was normal and proteinuria was absent. Serological evaluation for hepatitis B and C, Epstein-Barr Virus (EBV), Cytomegalovirus, Herpes simplex, Chlamydia, Mycoplasma, Rickettsia conorii, Coxiella burnetti, Toxoplasma, Borrelia, Aspergillus, Candida, agglutination test for Brucella were negative. Blood, urine and stool cultures were also negative. Tuberculosis was discarded by acid-fast stained smears and culture. Laboratory evaluation for systemic or malignant diseases were negative (antinuclear antibodies, anti-DNA antibodies, antiphospholipid antibodies, anti mitochondrial antibodies, anti smooth-muscle antibodies, rheumatoid factor, Antineutrophil Cytoplasmic Antibodies (ANCA), cryoglobulins, tumor markers). Chest x-rays, ultrasound examination, and echocardiography were normal as well. The temporal artery biopsy and the bone marrow examination were normal. We diagnosed AOSD according to the Yamaguchi criteria and we started a steroid therapy (prednisone: 1mg/kg/day). The symptoms began to improve. Ten months later, she presented the same clinical picture. X-rays of both hands showed bone erosions at the carps. We used oral methotrexate in weekly dose of 10mg. 8 months later, the patient developed an ulcerated tumor at the scalp with cervical lymph nodes whose biopsy revealed a squamous cell carcinoma. Methotrexate was stopped and she was treated with chemotherapy and radiotherapy. She did not present a recurrence during a 12 months follow up period. | adult-onset still’s disease, paraneoplastic syndrome, squamous cell carcinoma | Not supported with pagination yet | null |
PMC7394668_01 | Male | 3 | A 3-year-8-month old male presented with a violet skin lesion and a swelling below his right knee which was first noticed at an age of 7 months. The swelling gradually increased in size over the next two years and was associated with pain, low grade intermittent fever and decreased appetite. At this time a radiograph was obtained which revealed lytic areas involving head and proximal shaft of right tibia and fibula (images not shown). An exploration of lesion was done in December, 2015 and histopathology revealed fibrofatty tissue with evidence of chronic inflammation. A provisional diagnosis of osteomyelitis was made and treatment with broad spectrum antibiotics was initiated. However, there was no symptomatic relief and the swelling progressed in size. After a repeat imaging, 2nd debridement was done in June, 2016 (Fig. 1a) and antibiotics were continued. Histopathology on this occasion showed normal bone with few areas of necrosis and no evidence of granuloma or malignancy. Despite surgery, the symptoms persisted and 3rd debridement was done in December, 2016. Results were again disappointing and he was started on empirical ATT from April, 2017 (Fig. 1b).
He presented to our hospital in August, 2017. The child had a swelling below knee over the right leg which was hard in consistency. The skin over the tumor was of violet color with increased temperature. The child had a poor nutritional status. His complete blood counts were suggestive of anaemia, leucocytosis and normal platelet count. Liver and kidney function tests were normal. Peripheral smear revealed microcytic and hypochromic RBCs. Bone marrow studies were normal. Workup for primary immunodeficiency, bacterial/fungal infection and tuberculosis was negative. A radiograph of right leg showed lytic sclerotic destructive lesion with midzone of transition seen involving right proximal tibia and fibula with soft tissue component (Fig. 1c). MRI done in 2016 and 2017 (Fig. 2) revealed destruction of the right proximal tibia and fibula with marrow oedema, oedematous changes in surrounding soft tissue, atrophy of the calf muscles and a sinus tract due to prior surgical interventions. A bone biopsy was done which showed fibro-collagenous tissue with mild chronic inflammation. He was considered to have chronic tubercular osteomyelitis and continued on ATT till August, 2018 with no response. A repeat biopsy of the lesion in August, 2018 showed a tumor with nodular architecture. Immunohistochemistry was positive for CD34, FLI-1 and CD31 (Fig. 3). It was negative for EMA, desmin and myogenin. Skin biopsy showed features of acanthotic epidermis with dense fibrosis in the dermis and similar tumor in deep dermis. Bone biopsy had infiltration of bone by similar tissue. Fat biopsy showed fibroadipose tissue with vascular proliferation. A diagnosis of KH was made and he was referred to our sarcoma clinic in September, 2018. He was started on treatment with propranolol at a dose of 0.6 mg/kg twice a day for 1 week followed by 1.1 mg/kg for 2 weeks and 1.7 mg/kg thereafter along with prednisone at 2 mg/kg. On follow-up after a month child was better; with a slight decrease in size of swelling and pain and was able to sleep without analgesics. His appetite improved. On follow up at 3 month he had an excellent clinical response. Imaging with MRI at 5 months revealed a near complete resolution. He developed cushingoid features on steroids which resolved on tapering of steroids.
The treatment plan for surgery was discussed with parents. However, parents have preferred to defer any extensive surgery and decided to continue with medical management. | kaposiform hemangioendothelioma, propranolol, steroids | Not supported with pagination yet | null |
PMC5473387_01 | Female | 47 | A 47- year-old woman with no significant medical history was referred to our center with pain in the interphalangeal joints of the hands and the knees and ankles, erythematous nodules on shins, and swollen eyebrows. The symptoms had appeared 2 months before the patient's referral.
On clinical evaluation, polyarthritis along with symptoms of erythema nodosum-like nodules and low-grade fever was detected. Distinct red papules were visible above the eyebrows (Figure 1).
Results of routine hematological and biochemical tests including serum calcium were normal. Immunologic tests including anti-nuclear antibody (ANA), rheumatoid factor (RF), and tuberculin test were negative. Additionally, the erythrocyte sedimentation rate (ESR) was 51 mm/hr (normal range: 0-29 mm/hr for women), angiotensin-converting enzyme (ACE) level was 73 U/L (normal: less than 40 U/L), and C-reactive protein (CRP) level was 48 mg/L (normal: less than 10 mg/L). The patient reported a history of multiple tattooing over the eyebrows, and the last tattooing was performed 4 months before her present symptoms manifested.
Considering the presence of erythema nodosum and bilateral ankle arthritis, computed tomographic scan (CT) of thorax was performed, which showed bilateral hilar adenopathy with reticulonodular lesions in lower lobes of the lung (Figure 1). The laboratory test of tuberculosis performed via direct examination and culture of the sputum was negative. The diagnosis of Lofgren's syndrome, an acute form of sarcoidosis was confirmed based on the presence of the triad of erythema nodosum, bilateral hilar lymphadenopathy, and polyarthritis.
Considering a 99.95% positive predictive value of Lofgren's syndrome for the diagnosis of sarcoidosis, biopsy was not advised.
Prednisolone 30 mg/day along with azathioprine 100 mg/day as a steroid-sparing agent were administered to the patient. After a follow-up period of 6 weeks, improvement in joint and cutaneous symptoms was observed. However, a four-fold increase in the liver enzymes led to the discontinuation of azathioprine. Subsequently, the prednisolone dose was tapered to 2.5 mg weekly. However, at the next follow-up one month later, due to increased inflammation and erythema of the eyebrow lesion along with recurrence of previous symptoms, the dose of prednisolone was increased to 50 mg/day and intralesional corticosteroid injection was administered as well. Methotrexate (MTX), 15 mg injection per week, was also added to the treatment as an alternative steroid-sparing agent. However, no improvement was observed after 8 weeks.
Eventually, a biopsy of the eyebrow was recommended. However, due to the fear of a post-biopsy scar, the patient refused to undergo biopsy. Following the patient's complaint of increased appetite and weight gain but no improvement in symptoms, treatment with subcutaneous adalimumab 40 mg (one ampoule) every 2 weeks along with 10 mg prednisolone was started. The inflammation and erythematous papules disappeared in 2 weeks after the first injection (Figure 2). A follow-up chest CT after 4 weeks showed no significant abnormality. Subsequently, prednisolone was tapered and withdrawn over a period of 3 months, and adalimumab was continued as monotherapy.
Despite the early evidences of adalimumab effectiveness in sarcoidosis treatment, there is no standard protocol for such intervention. We administered two ampoules of adalimumab subcutaneously every month (80 mg in total), as suggested for rheumatoid arthritis.
After 2 months of adalimumab treatment, increasing intervals between the injections from 2 weeks to 3 weeks (one 40 mg adalimumab ampoule per 3 weeks) led to the re-emergence of symptoms, which required a subsequent interval reduction to 2 weeks again. After 9 months of follow-up, the patient is still receiving adalimumab as monotherapy, and no sign of disease recurrence has been observed. | adalimumab, eyebrow, refractory sarcoidosis | Spinal CT scan of Thorax with IV contrast showing systemic hilar and mediastinal adenopathies with subtle reticulonodular lungs infiltration compatible with sarcoidosis. |
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PMC3975195_01 | Male | 65 | We describe a 65-year-old patient with long-standing type 2 diabetes mellitus who presented with a 2-year history of papular lesions about 3-4 mm in diameter, hyperkeratotic, very itchy and located primarily on the back (fig. 1). Laboratory tests were unremarkable. A skin biopsy was taken. The hematoxylin-eosin stain showed an ulcerative lesion with collagen fibers, keratinous material and lymphocytic infiltration. The lower edge of the ulcer was interrupted by collagen fibers running perpendicular to it (fig. 2). These findings were consistent with APC. Use of topical corticosteroids and antihistamines did not result in any improvement of the skin lesions.
The lesions were treated for 2 months with topical tacalcitol (once daily) and disappeared completely (fig. 3). However, 4 weeks after finishing the treatment, the lesions recurred less severely, showing an early recovery after reintroduction of tacalcitol during 3 weeks. Now, the patient is treating himself when the lesions recur using the same treatment with full recovery between outbreaks. | acquired perforating collagenosis, elastosis perforans serpiginosa, perforating collagenosis, tacalcitol, vitamin d3 analogues | Not supported with pagination yet | null |
PMC4241320_01 | Female | 66 | We present the case of a 66-year-old woman referred originally to Dartmouth-Hitchcock Epilepsy Center in 2010 for seizure disorder. In her 20s, she was involved in a motorcycle collision for which she was hospitalized for one week. No known traumatic brain injury (TBI) was diagnosed. Then she developed migraine headaches later, becoming more severe in her 30s. Also in her 30s and 40s, she developed fainting episodes. When she was standing for a long time, she would tumble down and get up. If she stood quickly, she would lose her vision. Those were diagnosed as syncope and were present all her life. It also seemed to run in her family.
Then, in 2007, she developed what she thought were seizures. They occurred when she was lying in bed. She would wake up and shake in the middle of the night. She would not lose consciousness. They were diagnosed as nonepileptic seizures (NES). Of note, the patient denied having any history of trauma, stressful life events, or other current stressors that might have triggered spells.
The patient initiated levetiracetam but nevertheless continued having events where she started whole-body shaking, lasting 5 to 10 minutes. She described having two recent events where she only had shaking of her right hand, arm, and face. After this event, her eyes were closed and she was very tired and slept for several hours. She had two of those right-sided events. All other events previously have included whole body shaking.
In the summer of 2008, she had an event where she was walking to the bathroom at night, she crashed down on the floor, had raccoon eyes and bruises, and was hospitalized elsewhere. There she had tilt table testing, which was positive and she was diagnosed with syncope; however, she was also noted to be hypertensive. She was not started on any medications during that outside hospitalization but was advised to sit at the edge of the bed and stand up slowly.
She also complained of having comprehension difficulties and poor memory, citing difficulties doing the laundry. At times, she was incapable of using a coffee maker that she has used for a long time and her husband confirmed that those events were more frequently occurring. She had not been sleeping very well and had difficulties concentrating. She denied feeling depressed. Physical exam found no cog-wheeling but falling diffusely with positive Romberg's and her eyes closed. She also had difficulties performing tandem gait but was able to walk on her heels and toes. The plan was for her to be admitted for video EEG (VEEG) monitoring and to have neuropsychological testing.
VEEG monitoring six weeks later in April 2010 captured multiple NES but no episodes with ictal correlates. She was discharged with outpatient follow-up outside our institution. A year later, in March of 2011, she re-presented with the chief complaints of headaches and did not have any significant NES spells. At this time, it was noted that while she did not have psychiatric care, she was taking both citalopram and clonazepam as prescribed by her primary care physician (PCP).
Half a year later in September 2011, the patient was seen with the chief complaint of headache as well as worsening depth perception. She was prescribed topiramate for her headaches and considered usage of amitriptyline, although patient was concerned about possibility of weight gain as had happened in the past. The patient was counseled on nonpharmacologic treatments of both anxiety and sleep hygiene. Nine months later in June 2012, the patient first described having more frequent falls as well as worsened headaches. For her symptoms, she was increased on topiramate prescribed hydroxyzine for moderate headaches and zolmatriptan for more severe headaches. The patient did not exhibit significant clinical improvement.
Then, in May 2013, the patient and her family described having hallucinations nearly every night, which consisted of the patient's witnessing other people talking to each other, but never to her directly. These people never talked to her or told her to do things. She denied these as the typical auditory hallucinations worrisome of primary thought disorders consisting of running commentary about the patient's own behavior. The auditory hallucinations were also never present in the absence of visual hallucinations. The visual hallucinations were nonhostile, but the patient's emotions associated with them were of fear due to uncertainty of the intentions of the people she was experiencing. However, she "knew that these people weren't really there" and that when she "turned on the lights, they would disappear." She also described episodes where she was confused and had wandered about. This happened in late February and again early March 2013. Although she had been living in the same house for 37 years, it did not feel like the same house to her.
Visual symptoms included "seeing blue spots under my eyes on the left as well as on my hands." Fundoscopic exam revealed floaters. The patient reported seeing cracks in the wall when looking at a white wall. The patient's husband reported that "she is becoming very forgetful." These hallucinations were thought to be associated with nortriptyline, and dosage was reduced to 10 mg PO at night. It was first thought and documented at the end of May 2013 that the patient may have a neurodegenerative disease especially given significant atrophy of her frontal lobes as evidenced on magnetic resonance imaging (MRI). Four months later, her falls and headaches continued, although now she was "hearing voices that are not threatening." The goal had been to decrease her nightly clonazepam dosage to see if this would allow hallucinations to improve. Of all her concerns, her headaches were causing the most misery.
At this point, referral to embedded psychiatric clinician within the neurology outpatient clinic occurred. The patient met our newly established quality improvement referral criteria by scoring above a certain threshold on depression screening. She was seen initially at the end of November, 2013. In addition to confirming her history above, it was found that family history was significant for early-onset Alzheimer's disease in the patient's brother. Physical exam did not find any cog-wheeling, rigidity, shuffling gait, or gait instability. Mental status exam revealed appearing younger than her stated age, anxious mood and flat affect, and thought content revealing the belief that "there are migrant French-Canadian workers at home threatening to hurt my family members." She had seen them at least twice or thrice.
Her Montreal Cognitive Assessment (MOCA) score was 20/30 (score breakdown: 3/5 on visuospatial/executive: missed trails and did not get hands of clock correct; attention: 5/6: missed serial 7 subtraction; language: 2/3: did not repeat sentences perfectly with regard to pronouns, singular versus plural; delayed recall: 0/5, but recalled all five with category cuing; orientation: 5/6. Her PHQ-9 and GAD-7 scores were 7 and 9, resp.).
It was thought that it would be exceedingly rare, although not impossible, for the patient to have a new-onset psychosis at this age. However, the patient's description of her symptoms was not classically Charles Bonnet syndrome, as she experienced "real people talking and interacting" in addition to just seeing them. We decided to re-do MRI and obtain dementia workup, including B12/folate, and other basic labs, which were all unremarkable.
At our second appointment several months later, we again noticed the constellation of visual hallucinations, cognitive impairment, and history of multiple falls despite not having any clear Parkinsonian features on physical exam. At this appointment, both the patient and her family were more significantly distressed by especially the auditory hallucinations component of her experiences, described as "little people threatening to do things to me or my family." Her PHQ-9 and GAD-7 scores had worsened to 10 and 17, respectively. MRI was unchanged compared to a year ago. It was thought at this time that the patient's distressing symptoms as well as psychotic symptoms could benefit from trial of quetiapine, to which the patient was naive. Concurrently, we aimed to decrease clonazepam dosage from 3 mg to 2 mg per day over several weeks.
At our 3rd appointment, a month later, the patient reported that "everybody is noticing the difference with the Seroquel (quetiapine)." In fact, she described no longer having any AVH. Her quetiapine dosage had been titrated to effect to 200 mg PO QHS. Her PHQ-9 and GAD-7 scores were both zero. Of particular significance was also that the patient had tapered off clonazepam completely. As a result, both her headaches and her memory complaints had also decreased. The patient stated that since she was doing so well, she declined formal MOCA retesting.
However, at our 4th appointment, two months since the previous one, the patient described having horrible headaches and having hallucinations again, described as "I see people in the bathroom dressed in regular clothes, and they just stand there without talking to me." The patient and her family did not seem to think that her headaches and hallucinations were connected. She also stated that sleep was awful despite taking hydroxyzine, melatonin, and quetiapine concurrently. We thus decided to transition her sertraline to venlafaxine using cross-titration.
At our 5th appointment a month and a half later, the patient had in the interim requested increasing quetiapine from 200 to 300 mg PO at night, and she was noticeably improved with both increase of quetiapine and transition from sertraline to venlafaxine. In fact, her headaches were "now gone completely" and her mood symptoms were also improved: "The new medication is a happy pill!" The patient described having minimal auditory and visual hallucinations which were "no longer bothering me."
Approximately 8 months following her initial presentation, the patient described "things as going very well": she was no longer waking up in the morning with any headaches and felt comfortable with seeing "little happy faces at night" when either falling asleep or waking up. At this point, the patient's venlafaxine dosage was 225 mg PO QDay and quetiapine dosage was between 300 and 400 mg PO at night. Given the patient's historical lack of depth perception and known history of floaters, it was thought that Charles Bonnet syndrome could be considered due to response of patient's AH to quetiapine but not her visual hallucinations. The patient was educated about the possibility that she had Charles Bonnet syndrome in addition to meeting criteria for major depressive disorder with Psychotic Features and she was reassured.
Ten to twelve months following her initial presentation, the patient described having a significant improvement in mood symptoms, and clinical exam and family collateral information indicated her Major Depression was in remission. The patient's medication dosages of venlafaxine 225 mg daily and 400 mg quetiapine at night were stable and did not cause any noticeable adverse effects, and discussion about eventually trying to find the minimally effective dose:especially in the case of the latter medication, due to concerns for potential metabolic and extrapyramidal adverse effects:ensued, although the patient and her family wanted to continue the current dosage given lack of any psychiatric symptoms. | null | Not supported with pagination yet | null |
PMC9275669_01 | Female | 37 | As an illustration of the misophonia model we use the case conceptualization of an actual patient given the anonymized name of "Charlotte." This patient meets all criteria proposed by the Amsterdam UMC in 2020. The revised Amsterdam Misophonia Scale [AMISOS-R; ] indicates she has severe to extreme misophonia (range 31-40). The labels in parentheses are links to the main elements of Figure 3.
Charlotte is a 37-year-old woman, who works as a lawyer and has a family with two children. Charlotte signed up for treatment, because she wants to avoid a divorce. She considers treatment as "her last straw to save her marriage." Charlotte developed her symptoms at the age of 12, when she started puberty. She has always had high standards as a child (personality), but she started judging people who made more eating sounds and even disliked them. Now she considers people who make eating sounds as "people who have a defect" and refuses to interact with them. Her parents do not have misophonia, but she found out her father's mother had similar symptoms (genetic disposition). Charlotte grew up in a prosperous family as an only child. Her first and main trigger sound was the sound of food chewing her mother made. During her adolescence all joint meals were in a tense atmosphere, with her mother expressing she was hurt by the non-verbal aggression of Charlotte, and her father "trying to mediate between them." Sometimes Charlotte was allowed to listen to a portable music player during dinners, but more often she was told by her father to stay at the table and control herself. This made her feel extremely powerless and she felt guilty for ruining dinner (learning history). During holidays, without her busy schedule of extracurricular activities, misophonia symptoms were less present. With lower stress and, as such, less sensitivity to misophonic triggers, she could enjoy her mother's company more (environment). Later in life she felt annoyed by nearby eating behaviors of students or colleagues, but misophonia symptoms were not disabling, because she could avoid her major triggers. When she visited her parents however, misophonia symptoms returned to levels that were present at puberty. The first 6 years of her relationship with her husband, she did not experience him as a misophonia trigger. But during the pregnancy of their firstborn child, she started to respond with disgust and aggression (emotion) to his eating sounds and breathing or snoring. She also had a strong reaction to the sounds of doors closing loudly, whispering, sniffing, "s" and "t" sounds, glasses being put on the table, ringing keys and the dishwasher during nighttime (trigger sound). She developed a strong focus on these sounds, which made it impossible to engage in social interaction or sleep during these sounds (hyper focus). Subsequently Charlotte avoided eating together with her family and started sleeping alone. She tried to correct her husband when he was eating, even though she realized he did not produce too much sound, and she picked many fights about his breathing sounds (coping).
Results of the protocol are illustrated by the case study of Charlotte. Even though Charlotte was anxious at first to adopt new triggers from other patients, she did not. After treatment she experienced a large reduction in misophonia symptoms. Although she was still experiencing some symptoms, the relationship with her husband improved significantly. After treatment Charlotte was able to eat and sleep together again. She could make jokes with her husband about her misophonia (for example saying "Just breathe!," when she got annoyed) and the tension at home decreased. She lost the hyper focus on most trigger sounds. The eating sounds of her mother remained a trigger for Charlotte, but she no longer avoided eating with her parents. She was able to cope in a functional manner when an emotional reaction was provoked. Charlotte stated she felt more relaxed and free in social interactions with other people.
At session 1, 4, 7, and 8 progress was monitored by two questionnaires; the AMISOS-R and SCL-90. Charlotte started treatment with severe to extreme misophonia (range 31-40) and at the end of treatment her symptoms were reduced to mild misophonia (range 11-20). Also, general psychopathology decreased from a very high level to a level above average (see Figure 6). | cognitive-behavioral therapy (cbt), group treatment methods, misophonia, protocol and guidelines, psychotherapy | Not supported with pagination yet | null |
PMC4532025_01 | Male | 41 | A 41-year-old man was admitted to our hospital because of generalized purpura and productive cough. He was well until 2 months earlier when he developed productive cough with whitish mucoid sputum and exertional dyspnea. At that time, he was admitted to a local hospital and treated with antituberculous agents for pulmonary tuberculosis confirmed by positive sputum for acid-fast bacilli (AFB). Forty five days before entry, he noticed generalized purpura, more prominent in the lower extremities, and mild pretibial edema. Ten days before admission, high fever and generalized weakness occurred in spite of antituberculosis medication.
He was a government employee and nonsmoker. His past medical history was noncontributory. There was no history of previous nausea, vomiting, abdominal pain, constipation, diarrhea, weight loss and arthralgia.
On examination, he was febrile state, temperature 38.1 C, with a blood pressure of 130/90mmHg, a respiratory rate of 20 per minute, and a heart rate of 112 beats per minute. Multiple, 0.5 x 0.5cm sized, nontender cervical lymph nodes were detected. The conjunctivae were pale. Coarse breathing sounds were heard over the both lung with rale. His bowel sounds were normal and there was no evidence of hepatosplenomegaly. Numerous nontender palpable purpura, located primarily on the lower extremities, were present with pretibial pitting edema (Fig. 1).
The chest roentgenogram taken on admission revealed diffuse scattered, ill defined nodules in entire both lung fields and patchy and confluent density in both upper lungs(Fig. 2). Abdominal ultrasonogram showed increased echoes of renal parenchyme with upper normal size. Others were not remarkable.
The hemoglobin was 9.0g/dl, with 2.8% reticulocytes. The hematocrit was 27.2%. The white blood cell count was 14.3 x 109/L, with a differential of 75% neutrophils, 20% lymphocytes, 3% monocytes, 1% eosinophil and 1% atypical lymphocyte. Wintrobe erythrocyte sedimentation rate was 65 mm/hr(corrected 18 mm/hr). The platelet count was 438 x 109/L. The antiplatelet antibody was negative. The prothrombin time and partial thromboplastin time were within normal limits. Blood chemistry revealed total serum protein 5.8 g/dl, albumin 1.7 g/dl, AST 65 U/L, ALT 23 U/L, triglyceride 109 mg/dl, BUN 22.5 mg/dl, creatinine 1.5 mg/dl, calcium 7.6 mg/dl and phosphate 5.1 mg/dl with normal serum electrolyte. The serum Ig A was 640 mg/dl, Ig G 2020 mg/dl, Ig M 150 mg/dl and Ig E 831 IU/ml. The serum C3, C4 were 162, 37.8 mg/dl, respectively. The urinalysis was reported as showing 300 mg/dl of proteinuria, 20-25 red blood cells, 3-5 white cells per high-power field and WBC cast. Sixty-five percent of the red cells were dysmorphic. In a 24-hour specimen of urine, protein was 6930 mg, creatinine 693 mg. A serum protein electrophoresis revealed hypoalbuminemia with increased gamma globulin fraction and urine electrophoresis showed protein losing pattern. Stool specimen gave a negative test for occult blood. The tests for antistreptolysin O titer, ANA, LE cell, VDRL, hepatitis B surface antigen and antibody and rheumatoid factor were all negative.
Cultures of blood remained sterile. The arterial blood gas showed pH 7.37, PCO2 32.4 mmHg. PO2 71.6 mmHg, HCO3 18.9 mmol/L. The pulmonary function studies showed that FEV1 was 2.04 L(62% predicted). Three separate smears of sputum for AFB were negative. The antituberculous chemotherapy was begun with isoniazid (300 mg), ethambutol (800 mg), rifampin (450 mg) and pyrazinamide (1.5 g), all once daily with pyridoxine. A punch biopsy specimen of the palpable purpuric lesions on the posterior aspect of the leg was consistent with the diagnosis of "leukocytoclastic vasculitis" (Fig. 3). The hospital course was complicated by continued hematuria and proteinuria. The skin lesions slowly resolved by antituberculous agents. The patient was discharged nineteen days later and then readmitted five weeks later for renal biopsy.
On readmission, clinical signs were improved and the pulmonary lesions on chest X-ray film were slightly cleared. Renal biopsy was performed. Light microscopy demonstrated mesangial cell hyperplasia and widening of mesangial matrix. There were fibrous crescents associated with adhesion of Bowman's capsule (Fig. 4). There was the evidence of interstitial chronic granulomatous inflammation with caseous necrosis, with moderate fibrosis, lymphoplasmacytic infiltration, compatible with renal involvement of tuberculosis(Fig. 5). Immunofluorescent findings were strong nodular mesangial Ig A deposit with trace granular Ig G deposition along peripheral capillary loops and perivascular C3 deposit(Fig. 6).
Thereafter, antituberculous drugs were administered for 12 months. He completely recovered from the pulmonary and renal manifestations and remained symptom free in 24 months after antituberculous drugs started. | null | Not supported with pagination yet | null |
PMC6125801_01 | Female | 49 | A 49-years old Caucasian woman was admitted at our Emergency Department with shortness of breath and mild respiratory discomfort. She has no significant past medical history and she has never smoked. No history of cough, fever, weight loss or night sweat had been detected. There were no allergies, no exposure to active tuberculosis, but she reported a history of exposure to asbestos. Cardiovascular examination was normal. There was no significant lymphadenopathy or thyromegaly. Respiratory sounds were impaired on the right lung. No abnormalities were detected in blood chemistry.
A first chest X-Ray (Fig. 1) executed in posterior-anterior (PA) and lateral projection, showed multiple nodules, hilar-mediastinal enlargement and nodular radiopacity at right hilum; also, pleural effusion on the right lung and obliteration of ipsilateral costophrenic angle was detected.
Abdomen Ultrasound (US) has been performed in order to exclude any pathological masses, primary neoplasm or metastatic disease. As collateral findings, US confirmed the pleural effusion with multiple solid rounded masses at pulmonary bases (Fig. 2).
Total-body CT scan was performed using a Lightspeed VCT 64-slice (General Electric, Boston, Massachusetts USA), with a pre-contrast phase, and a parenchymal phase, 70 s after administration of 120 mL of non-ionic contrast agent injection (350 mg l/ml, 2,5 mL/s.). The CT (Fig. 3), revealed a large mediastinal mass overrunning the right hemithorax, with pleural free fluid and multiple solid pleural masses on the right. No displacement of mediastinal structures has been noted. After injection of iodinated contrast, the lesions appear hypo-vascular, with enhancing margins, internal lobulation and septation, and few calcific spots. No direct endoluminal invasion in the main mediastinal vessels has been detected.
Contrast Enhanced CT (CECT) scan of abdomen, pelvis and brain was negative.
During the hospitalization the patient underwent to 18 [F]-fluorodeoxyglucose (FDG)-PET (Fig. 4): the patient received intravenous injection of 18[F]-FDG (radioactivity: 371 m Bq) and rested for 45 min before PET-scan. The mass showed an increased uptake involving the parietal, mediastinal and diaphragmatic pleura of right lung. Two Region of Interest (ROI) were positioned (Fig. 5): the first one on anterior chest wall (ROI 1: SUV 3,6), the second one near the posterior cost-vertebral arch (ROI 2: SUV 4,4) and maximum standardized uptake values were calculated.
Subsequently a CT-guided percutaneous biopsy (14 G cutting needle) of the mass in the right hemithorax was performed. Histopathological examination (Fig. 6) revealed a tissue made-up by bands of sclerosis and average size lymphocytes with T-immature phenotype (precursor T cell, CD3+, CD5+/-, CD4+, CD8+, TdT+), associated also with irregular oval shape epithelial cells (CKAE1-AE3+, Calretinin-).
The above-mentioned histological findings are consistent with thymoma type B2 (cortical).
After definitive diagnosis of thymoma and disease staging, the patient chose to receive treatment in another Institute and so we lost her to follow-up. | 18[f]-fdg, 18[f]-fluorodeoxyglucose, cect, contrast enhanced computed tomography, ct, computed tomography, computed tomography, itmig, international thymic malignancy interest group, mri, magnetic resonance imaging, pa, posterior-anterior, pet, positron emission tomography, pleural thymoma, positron emission tomography, recist, response evaluation criteria in solid tumors, roi, region of interest, radiological staging, x-ray | Not supported with pagination yet | null |
PMC8426067_01 | Female | 17 | The first patient, a 17-year-old female, with no significant past medical history, presented with 1.5 months of facial angioedema, shortness of breath, chest pain, pleural effusion, acne-type rash, and visual loss. There was no history of recent medication prior to onset of symptoms, and a complete blood count was significant for eosinophilia. C1 esterase quantitative was normal. She had received antibiotics and antihistaminic at another facility. Imaging demonstrated diffuse lymphadenopathy and bilateral pleural effusions. Tuberculosis, autoimmune etiology including hereditary angioedema, rheumatologic etiology including sarcoidosis or systemic lupus erythematosus (SLE), and an oncologic process including lymphoma were excluded. 81% eosinophils were identified in the pleural fluid. Bone marrow biopsy was normocellular with trilineage hematopoiesis and approximately 30% eosinophils with some trilobed and multilobated forms. There was no increase in blasts, and some small hypolobated megakaryocytes were present (Figure 1). She was treated subsequently with steroid (prednisone, 60 mg/day and weaned gradually over seven months) alone, and the eosinophil counts dropped rapidly. Her overall eosinophil count remained slightly above the normal range afterwards. She still had some vision and sinus symptoms, but other symptoms resolved. Her absolute eosinophil count declined from 12.9 k/ul (normal 0.1-0.3 k/ul) to 0.4 k/ul over the course of the treatment and continued to remain within the normal range at one-year follow-up. | null | Not supported with pagination yet | null |
PMC8241529_01 | Male | 2 | A boy aged 2 years and 7 months came to the pediatric department with a generalized seizure for less than 5 minutes and immediately regained consciousness after the seizure. The child had a fever four days ago, continuous throughout the day, and was given a fever reducer. Other complaints were nonproductive cough, rhinorrhea, and shortness of breath two days before being admitted to the hospital. The patient also had diarrhea three times, but apart from the existing complaints, there were no other complaints such as sore throat, nausea, vomiting, stomach pain, and no clear history of COVID-19 exposure. The patient had a history of seizure at the age of six months, one year, and one and a half years and no history of tuberculosis infection and choking. On physical examination, the child looked weak and compos mentis; vital signs were as follows: pulse 120 x/min, respiratory rate 28 x/min, temperature 38 C, 98% oxygen saturation, cold extremities, and vesicular breath sound on thoracic auscultation found weakened at the upper right lung, no rhonchi, and no wheezing. From laboratory examination, the following data were acquired: haemoglobin level 11.8 g/dL, hematocrit 32.8%, leukocytes 27 x 109/L, thrombocyte 341 x 109/L, segment neutrophils 73.8%, lymphocytes 18.2%, NLR 4.1, and absolute lymphocyte count 4914/mm3. From blood gas analysis, the following data were acquired: pH 7.39, PCO2 24 mmHg, PO2 77 mmHg, HCO3 14.5 mmol/L, and base excess -9.2 mmol/L. An X-ray radiograph showed consolidation of the right upper lung (Figure 1) which represented superior right lobar pneumonia and bronchopneumonia. The result of the first SARS-CoV-2 nucleic acid test on the day the child was admitted was negative, but one day later, on the second test, the result was positive. The patient received antiseizure therapy, antibiotics, nebulization, and symptomatic supportive therapy. A nasal cannula was supported with two liters of oxygen per minute and intravenous fluid. The patient responded well to the therapy given and recovered in 12 days. | null | Not supported with pagination yet | null |
PMC7406454_01 | Male | 45 | A 45-year old male presented to the ED with mild fever, sneezing, rhinorrhea, cough, right-sided dull chest pain and shortness of breath. He was recently exposed to a co-worker suffering from 'flu' and started experiencing upper respiratory tract infection symptoms two days ago. He was nauseous, vomited several times and suffered from diarrhea. The persistent dull chest pain and worsening exertional shortness of breath for a day prompted the ED visit. His past medical history was significant for Crohn s disease for which he was not on any medication. The patient was a smoker of about half a pack per day and denied any history of alcohol or recreational drug abuse. He traveled to South Africa twenty-three years ago and didn t have any pet at home. No personal history of tuberculosis (TB) or known exposure to anyone with TB. He worked at a fast-food restaurant and did not have any family history of vasculitis or lung cancer. Vital signs on admission were, a blood pressure of 135/89 mmHg, a pulse of 124 beats per minutes, a temperature of 37.8 C, a respiratory rate of 23 breaths per minute and oxygen saturation of 94% on 5L oxygen via nasal cannula. Physical examination showed a young man in mild distress from tachypnea.
He appeared dehydrated. Chest auscultation revealed bronchial breath sound and coarse crackles in the right mid and lower lung zone, both anteriorly and posteriorly. The rest of the examination was normal. Blood work was significant for leukocytosis, 27.1 x103/micro L with neutrophilia of 88% and bandemia of 3%. The rest of the complete blood count and comprehensive metabolic panel were normal. His lactic acid was 1.5mmol/L, and procalcitonin level was elevated at 0.69ng/ml. The chest X-ray is shown in Figure 1. A computed tomography (CT) of the chest was performed and representative slices are shown in Figure 1. The respiratory viral panel was positive for coronavirus. Sputum gram stain and culture showed normal respiratory flora. Urinary antigen testing for legionella and pneumococcus were negative. A workup for vasculitic disorders was negative. HIV antibody test was also negative. A diagnosis of necrotizing pneumonia due to secondary bacterial infection in the setting of coronavirus infection was made. Staphylococcus aureus (SA) was strongly suspected to be the etiologic agent. However, the patient was less toxic appearing than what would be expected with SA necrotizing pneumonia and a subacute vasculitic disorder, like granulomatosis with polyangiitis, was also considered.
Cavitary pneumonia with a fungal pathogen and lung malignancy were other possibilities, but no significant risk factors, such as prolonged neutropenia, chronic steroid use or prior structural lung disease were present. The patient was started on linezolid and meropenem. High-flow oxygen was used to achieve acceptable oxygen saturation level. Repeat chest X-rays on day one, two and three are shown in Figure 2. A repeat CT scan was obtained on day three to identify the structural lung damage better (Figure 3). He developed progressive respiratory failure requiring intubation and mechanical ventilation. An ultrasound revealed complex pleural effusion (Figure 4). A chest tube was inserted and 1.4L of frank pus was drained. A large air leak was noted from bronchopleural fistula (BPF) due to rupture of the abscess cavity in the pleural space. Pleural fluid analysis showed 457,000 leukocyte per cubic milliliter with 99% neutrophil, pH 6.9, glucose < 10mg/dL, protein 4.3gm/dL and lactate dehydrogenase > 10,000 IU/L. The culture was positive for SAG, species S constellatus. The patient was treated with ceftriaxone with subsequent improvement. He got liberated from mechanical ventilation. The BPF resolved, and the chest tube was successfully removed (Figure 5). He was completely functional during his outpatient visit a month later. | necrotizing pneumonia, streptococcus anginosus group, lung abscess, pyopneumothorax | Not supported with pagination yet | null |
PMC8576349_01 | Unknown | 18 | Following the ATA guidelines, all patients included in this study were <= 18 yr old. Between June and December 2020, four patients were admitted to the Department of Head and Neck Surgery and selected for the transoral approach. All these patients had a preoperative assessment, including thyroid hormonal level tests, neck ultrasound examination, and fine-needle aspiration (in line with The Bethesda System for Reporting Thyroid Cytopathology:TBSRTC).
Inclusion criteria for TOETVA were as follows: (1) thyroid nodule (TBSRTC II-IV) <= 6 cm in size; (2) thyroid nodule (TBSRTC V-VI) <= 2 cm in size with no lymph node involvement; (3) total size of thyroid gland <= 10 cm in diameter per lobe.
Contraindications for TOETVA included (1) previous anterior neck surgery, (2) tracheal or esophageal invasion, (3) previous radiation to the head or neck, (4) recurrent laryngeal nerve palsy, (5) oral cavity infection, (6) uncontrolled hyperthyroidism, and (7) patients under 10 years of age or less than 30 kg of weight.
The surgical steps have been described in previous publications and are based on Anuwoong's technique. In brief, the patients were placed in a supine position. After intubation, three incisions were made in the oral vestibule for the insertion of endoscopic 5-10 mm trocars. To insert a 30-degree endoscope, a 5-mm central trocar is recommended, especially for pediatric patients. Working space was then created by using a hook cautery and/or an ultrasonic scalpel. Next, the strap muscles were retracted laterally with a transcutaneous suture. The pyramidal lobe was dissected and separated from the trachea. The isthmus was then divided, and the superior thyroid vessels were dissected and divided using an energy device. The upper parathyroid gland and then the recurrent laryngeal nerve (RLN) were identified. The thyroid lobe was dissected from the trachea and the RLN while preserving the lower parathyroid. The specimen was put into an Endo Catch bag and removed via a central incision (Figure 1). | toetva, pediatric thyroid cancer, thyroid cancer in children, transoral approach, transoral thyroidectomy | Not supported with pagination yet | null |
PMC10316205_01 | Female | 31 | A 31-year-old female with tender lump in left breast lump 4 months with pain and intermittent yellow colored nipple discharge (2 months) [Figure 1a]. Fine-needle aspiration yielded 10 ml of yellowish pus like material with cytological findings shown in [Figure 1b , c, and c (inset)].
What is the diagnosis based on cytomorphology?
Actinomyces
Tuberculosis
Non-Hodgkin's lymphoma
Ductal carcinoma.
Answer to the first question:
1. a. Actinomyces
What is the special stain used in such cases?
PAS
ZN
Gram
All of the above
None of the above.
What is the most common causative agent of breast abscess?
Staphylococcus
Streptococcus
Enterococcus
Pseudomonas.
Actinomycosis is a chronic infection caused by Actinomyces species characterized by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of infections caused by Actinomyces species ranges from classical invasive actinomycosis to a less invasive form of superficial skin and soft-tissue infection. It is an often relapsing granulomatous infection that characteristically crosses tissue planes and forms abscesses and sinus tracts. First described by Ammentrop in 1893, primary actinomycosis of the breast is very rare and most commonly caused by Actinomyces israelii which normally inhabits the mouth, colon, and vagina.
Breast actinomycosis is primary when inoculation occurs through the nipple. Secondary actinomycosis of the breast refers to the extension of a pulmonary infection through the thoracic cage in a process that can affect the ribs, muscles, and finally the breast.[] Primary actinomycosis infections are commonly caused by A. israelii. Actinomyces neuii is a less common cause of classical actinomycosis. Actinomyces of breast is an uncommon occurrence with very limited case reports in the literature. Most often, the diagnosis of Actinomyces breast is made based on cytological findings. Differentiating causative agents of breast abscess is challenging. Knowledge of this organism at this rare site is essential so that it could be considered in the differentials. Distinguishing breast actinomycosis from tuberculosis and other potential infectious conditions is possible through pathological examination.[] Cytomorphology helps in making the diagnosis. Microbiological examination aids in the confirmation of the same. Although breast is a rare site for Actinomyces infection, cytopathologists must be aware of its occurrence and consider this in their differentials while diagnosing breast lumps.
Answers to the additional questions:
2. c. Gram
3. a. Staphylococcus. | null | Not supported with pagination yet | null |
PMC9530976_01 | Male | 54 | On the evening of 14 April 2021, a 54-year-old male did not know that his slipper had fallen while walking, and did not respond to the family's inquiries. At about eight o 'clock in the evening, the patient had a fever, with the highest temperature of 41 C. After the local hospital gave diclofenac sodium symptomatic antipyretic, the temperature gradually decreased to normal. During this period, the patient did not answer questions.
At about 10 o'clock in the evening, the patient began to lift the right upper limb involuntarily. The next morning, the patient was found to have a poor response. He could open his eyes when people called him, but did not respond, accompanied by involuntary twitching of the right limb. There was no nausea, vomiting, palpitation, shortness of breath, and incontinence during the course of the disease. To seek further diagnosis and treatment, he came to our hospital and was admitted to our department by the outpatient clinic with "consciousness disorder to be examined." Past history: found diabetes for half a month, denied any other special history. Physical examination: T 37.3 C, P 98 times/min, R 20 times/min, BP 129/95 mmhg, drowsiness, no obvious abnormalities found in skin, mucosa, lymph nodes and cardiopulmonary abdominal examination, equal size and equal circle of bilateral pupils with 3 mm in diameter, slow light reflex, involuntary twitching of right limb, negative meningeal irritation sign, and no positive signs found in other nervous systems physical examination. Initial diagnosis of consciousness disorder to be examined: intracranial infection, secondary epilepsy?
Improve related examinations, blood routine: WBC 8.7 g/L, NE 76.4%, HGB 163 g/L, PLT 111 G/L, blood biochemistry: TBil 53.4 umol/L, NCBil 43.3 umol/L, SAA 21.4 mg/L. There were no abnormalities in the electrolyte, liver function, renal function, blood glucose, high-sensitivity C-reactive protein, erythrocyte sedimentation rate and coagulation function, as shown in Table 1. Electroencephalogram (EEG): the main rhythm of each lead was 10 HZalpha with medium and low amplitude, and the parietal and occipital region was dominant, with left and right asymmetry and poor amplitude modulation. The left lead had more rhythm and activity of 4-7 HZtheta with medium and low amplitude, and slightly more activity of 3-3.5 HZdelta, and the front head was very biased. Brain magnetic resonance imaging (MRI): multiple spots and bands of abnormal signals were found in the left insula and temporal cortex, T2WI and T2 flair showed hyperintensity, T1 flair showed isointensity and hypointensity, and GD-DTPA enhanced scanning showed no obvious abnormal enhancement, as shown in Figure 1. Cranial MRA, MRV, neck vascular color ultrasound, chest CT, electrocardiogram, and heart color ultrasound showed no abnormalities. The patients were treated with epilepsy control, brain edema prevention, brain cell nutrition, anti-infection, water and electrolyte balance and liver protection, and closely monitor the changes of vital signs and mental pupils.
On 15 April, the patient was drowsy, still had intermittent twitching of the right lower limb, and coffee residue-like substances were extracted from the gastric tube. It was considered that stress ulcers occurred, and stomach protection drugs were added. In order to find out the cause, a lumbar puncture was performed to check the cerebrospinal fluid, and the pressure was 300 mm water column. The routine and biochemical results of cerebrospinal fluid are shown in Table 2. The diagnosis was considered viral encephalitis or autoimmune encephalitis, and antiviral combined with gamma globulin were added to the treatment. The serum and cerebrospinal fluid samples were sent to BGI for etiological second-generation sequencing examination, and the cerebrospinal fluid and serum were sent to kangshengda company for autoimmune encephalitis antibody detection. Dynamic monitoring of blood routine, electrolyte, liver and kidney function, blood glucose, CRP, and other related indicators during hospitalization are shown in Table 1. On 16 April, the patient was delirious, with a Glasgow (GCS) score of 3 points. He still had intermittent right limb twitching, intermittent fever, thick breathing sound, decreased blood oxygen saturation, and it was difficult to maintain stable vital signs. So he was urgently transferred to the central intensive care unit (ICU), and ventilator are assisted breathing was performed after endotracheal intubation.
On 19 April, the patient became drowsy. After people shouted, he could open his eyes and move according to the instructions. He still had an intermittent fever, the highest temperature was 38.6 C, there was no headache, the activity of the left limb was normal, the muscle strength of the right limb was grade 3, and there was no limb convulsion. Spontaneous breathing had been restored and the ventilator had been evacuated, but it is still in the state of endotracheal intubation. The second generation sequencing results of cerebrospinal fluid showed that it was infected with pseudorabies virus with a coverage rate of 1.86%, see Figure 2 for details. There was no abnormality in the second-generation sequencing of serum, and the antibodies of cerebrospinal fluid and serum to autoimmune encephalitis were negative. After inquiring about the medical history, we learned that the patient had been engaged in the pig industry for a long time. The patient had a clear diagnosis of viral encephalitis and continues to receive antiviral treatment. Considering that some of the patients were prone to retinitis leading to blindness, we invited ophthalmology to consult. Eye ophthalmologist examination: there was no congestion in the conjunctiva, the cornea was transparent, and the pupils of both eyes were very small, about 1.5 x 1 5 mm, direct and indirect light reflection existed, and it was difficult to peep into the fundus through ophthalmoscopy. On 22 April, the lumbar puncture was rechecked, the pressure was 220 mm water column, the routine and biochemical results of cerebrospinal fluid were not significantly changed. On 24 April, the patient's mind improved, the activity of the right limb was still poor, and the pupils on both sides were equal round, with a diameter of 3 mm. Re-examination of cranial MRI showed that the left frontotemporal insula had abnormal signals and meningeal changes, and the possibility of inflammatory lesions was high, which was better than before. On 27 April, the patient still had fever, the highest body temperature was 37.8 C, and the right muscle strength was grade 3. After pulling out the endotracheal intubation, the respiration was steady.
On 29 April, the patient could speak clearly, but the speech did not accord with the scene, and he was restless intermittently. Physical examination showed that memory and calculation ability were decreased, bilateral pupils were equal in size and circle, 5 mm in diameter, right muscle strength was grade 4, Risperidone was added for symptomatic treatment, and the rest remained unchanged. Therefore, we asked for ophthalmic consultation. Ophthalmic examination: VOD: 0.25, VOS: finger/2.5 m, fixed pupils in both eyes, mydriasis, 5 x 5 mm, fundoscopy showed that the retina at the posterior pole was flattened, no obvious hemorrhage or exudation was found. Therapeutically, antiviral eye drops and other local treatments were administered locally.
On 04 May, the patient was conscious, without irritability, and the muscle strength of the right limb was further improved, but the vision was still unclear. After reexamination of lumbar puncture, the cerebrospinal fluid pressure was 140 mm water column, the protein content increased, and there was no significant change in the rest. On 5 May, invited ophthalmology to consult again. Ophthalmic examination: VOD: 0.1 (+ 4.75d / + 1.25d x 155 corrections no response), VOS: 0.1 (+ 5.00d / + 1.50D x 180 corrections no response); Intraocular pressure: od 14 mmHg, os 14 mmHg; There was no congestion in the conjunctiva of both eyes, the cornea was transparent, the anterior chamber was deep, the crystal was transparent, the pupils of both eyes were fixed and dilated, 5 x 5 mm, the pupil margin was adhered to the front surface of the lens, pigmented keratic precipitates (KP) could be seen in the pupil area, fundus: vitreous cavity was turbid, the boundary of the optic disc could be seen faintly, and white linear changes could be seen in the peripheral omentum; The right eye macular OCT showed that the morphology of the right eye fovea was recognizable, the inner surface of the macular retina was still smooth, and the local ellipsoid structure was slightly disordered, see Figure 2 for details. The OCT of the left eye macular did not cooperate. B-ultrasound showed vitreous opacity in both eyes. It is necessary to continue to give eye drops to the patient for treatment.
On 12 May, the patient complained of transient dizziness when he got up and moving, which disappeared after standing. Both eyes were still blurred, bilateral pupils were dilated to the edge, the light reflex disappeared. The patient asked to be transferred to a superior hospital for treatment. On 3 June, the patient came to the hospital for follow-up visit, and the pathological changes in both eyes were no better than before. Reexamination of MRI showed that the range of inflammatory lesions was slightly smaller than before. | ngs, cerebrospinal fluid, endophthalmitis, pseudorabies virus, secondary epilepsy, viral encephalitis | Not supported with pagination yet | null |
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