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PMC3247095_01 | Male | 46 | A 46-year-old male farmer born in Minas Gerais State, Brazil, presented with disseminated plaque-like, ulcerated skin lesions (Figure 1A-D). Laryngoscopy showed lesions on the pharyngeal, nasal, and laryngeal mucosa (Figure 1E). He was a heavy tobacco smoker and drank 1-2 L of rum daily.
The differential diagnosis included secondary syphilis, sporotrichosis, histoplasmosis, tuberculosis, chromomycosis, and leishmaniasis. The following serologies were negative: venereal disease research laboratory (VDRL), Chagas disease, hepatitis B surface antigen, hepatitis C antibodies, and human immunodeficiency virus (HIV). Biopsy showed granulomatous inflammation, and yeasts with birefringent walls and multiple buds with a rudder's wheel aspect, characteristic of paracoccidioidomycosis (PCM), were seen (Figure 2A and B). Enzyme-linked immunosorbent assay (ELISA) for rPb27 and rPb40 (highly specific for Paracoccidioides brasiliensis) was strongly positive.1
Treatment with itraconazole (200 mg/day) resulted in generalized swelling, necessitating cessation. Cetoconazole (200 mg/day) was started and used for 3 months without improvement. Sulfamethoxazole-trimethoprim (800/160 mg two times per day) was added, and 60 days later, there was substantial improvement of the skin lesions; laryngeal lesions resolved after 6 months.
PCM is the most prevalent deep mycosis in Latin America, and it is caused by dimorphic fungus Paracoccidioides brasiliensis.2 It has different anatomoclinical forms (acute/subacute or chronic/multifocal), and it may affect any organ or system. The mucocutaneous involvement, seen in the present case, is most common in the chronic form of the disease. Prolonged treatment is necessary to control the mycosis, and use of traditional antibiotics such as sulfamethoxazole-trimethoprim is very effective. | null | Not supported with pagination yet | null |
PMC2816348_01 | Male | 15 | A 15-yr-old boy complained of a one-year history of slowly progressive weakness of the right hand and forearm, which worsened in cold weather. He also sensed intermittent fasciculations in the right-hand and forearm muscles. Besides, he suffered from coarse hand tremor, particularly when writing. Quite recently, he has noted the weakness of the other hand of a similar nature. He has been very athletic in sport activities like basketball, and has grown as much as 30 cm (1 foot) in height over the past two years. His medical history was non-contributory, and he denied any allergic disease. None of his family members reported having similar symptoms.
A neurological examination revealed that he had a bilateral atrophy of intrinsic hand muscles and forearm muscles except for the brachiradialis, and the atrophy was worse in the right hand. However, the weakness was noted only in the right hand and forearm on manual muscle testing (MRC grade IV+) including elbow extension. The other muscles, including the brachioradialis, were normovolemic and exhibited normal power, referred to as "oblique" amyotrophy. The tendon reflexes were normal with flexor plantar responses from both sides. Cranial nerve functions were normal as well. No ataxia, or sensory disturbances, or extrapyramidal signs were noted.
Motor nerve conduction studies of the right median and ulnar nerves, which were recorded at abductor pollicis brevis and abductor digitii minimi, showed normal motor nerve conduction velocities (54 and 59 msec over the segment between wrist and elbow, respectively). CMAP amplitudes were still in the normal range (5.8 and 8.4 mV, respectively) in spite of the atrophy of those recording muscles. But terminal latencies were 4.0 and 3.4 msec when normal limits were 3.6 and 2.5 m/sec, respectively; and F-wave latencies, 29.4 and 33.3 msec when normal limits of both nerves were 28 msec. The measurements in the motor nerve conduction studies of the left arm exhibited the similar features, excepting that the left arm was less affected. Sensory nerve conduction studies of the bilateral median, ulnar, medial, and lateral antebrachial cutaneous nerves showed normal conditions. Electromyography illustrated actively denervated and reinnervated patterns in the bilateral triceps brachii, pronator teres, extensor digitorum communis, first dorsal interosseus, or abductor pollicis brevis. Muscles innervated by the fifth and sixth cervical roots, such as the brachioradialis, biceps brachii, or deltoid - as well as lower extremity muscles and the tongue - showed a normal electromyographic pattern. These clinical and electrophysiological findings were suggestive of either anterior horn cell degeneration or root lesions involving the seventh and eighth cervical and first thoracic segments of the cord.
Simple cervical spine radiographs showed neither abnormalities with the exception of a loss of physiologic lordosis, nor a misalignment of the vertebral bodies in the flexed neck position (not shown). T1- and T2-weighted cervical MRI in the neutral position were unremarkable with normal contour and signal intensity of spinal cord (Fig. 1, 3A). With the neck flexion, sagittal and axial cervical MR images showed an anterior shifting of the posterior wall of the cervical dural sac below the third cervical vertebral level compressing the cervical spinal cord from the fifth cervical to the first thoracic vertebral levels (Fig. 2A). The anterior-posterior diameter of the spinal canal was reduced to about 30% of that in the neutral position. On enhancement, the widened posterior epidural space displayed a homogeneous strong enhancement with some signal flow void, suggesting a passively widened epidural venous plexus (Fig. 2B). The sixth and seventh cervical spinal segments were dynamically compressed when the patient flexed his neck forward, and the compression was more pronounced on the right side than on the left (Fig. 3B).
After confirming the compression of cervical cord on neck flexion, motor evoked potentials as well as median and posterior tibial somatosensory evoked potentials were performed both in anteflexion and in the neutral position of the neck. The results were turned out normal without a consistent latency prolongation between these two positions (central motor conduction time [CMCT] in the right abductor digitii quintii=8.1 and 8.6 msec, respectively; CMCT in the right abductor hallucis=16.9 and 16.6 m/sec, respectively).
Since the initial evaluation, two years have elapsed and no further progression has been noticed until now. | null | Not supported with pagination yet | null |
PMC5554978_01 | Male | 29 | A 29-year-old man with history of unrepaired congenital heart disease was transferred to our hospital for the management of a symptomatic right parietal mass. He had been in his usual state of health until 6 days before presentation when he developed sensory loss in his left foot that persisted for 24 h. He presented to an outside emergency department where he had a normal computed tomography (CT) without contrast of the head and normal CT angiography of the chest, abdomen, and pelvis. Outpatient neurology follow-up was recommended, but his symptoms progressed rapidly during the following days to include complete left-sided body weakness, numbness, and focal convulsions of his left upper and lower extremities. On Day 5, he presented again to the outside hospital, where magnetic resonance imaging (MRI) of the head revealed a right parietal ring-enhancing lesion consistent with cerebral abscess. Antibiotics were held to increase potential yield of abscess drainage culture, and the patient was started on levetiracetam with subsequent reduction in focal convulsions. He was then transferred to our hospital for neurosurgical intervention.
The patient was originally from Pakistan and moved to the United States in 2006. At age 5, he was diagnosed with truncus arteriosus Type II, bicuspid truncal valve, and single ventricular septal defect. He was not a surgical candidate because of progression of disease and subsequently developed Eisenmenger's syndrome with pulmonary hypertension, which was managed with nocturnal oxygen (4 L/min) and sildenafil. He had no recent travel and he last travelled to Pakistan in 2007. He worked as a part-time driver for taxi and fast-food companies and was not involved in any outdoor activities. He denied any sick contacts, personal history of or known exposure to tuberculosis, or incarceration. He had a significant remote history of recurrent dental problems requiring tooth extractions and outpatient oral antibiotic courses. His last visit to the dentist was for routine cleaning one year prior. The patient lived locally with his wife and denied any use of alcohol, tobacco, or other drugs.
On arrival to the emergency department, he had a temperature of 36.7 C, heart rate of 88 beats/minute, respiratory rate of 27 breaths/minute, blood pressure of 120/69 mm Hg, and oxygen saturation of 92% on 4 L nasal cannula. Physical examination revealed a fatigued, thin, but well-nourished man in no acute distress. He was alert and oriented to time, space, and person. On neurologic examination, he had 4/5 strength and a sensory deficit to light touch of his left upper and lower extremities. Tone and reflexes were normal throughout. Head and neck exam did not reveal any sinus tenderness, signs of trauma, otorrhea, Roth spots, oropharyngeal exudate, or palpable cervical lymph nodes. He did have notably poor dentition with visible caries and gingivitis. Cardiovascular examination was remarkable for a known II/VI systolic ejection murmur at the left sternal border and a soft diastolic murmur and he did not have any jugular venous distention. Pulmonary and abdominal examinations were within normal limits. He had clubbing bilaterally but no peripheral stigmata of endocarditis. Extensive review of systems on admission was negative except for what has already been mentioned and frequent gingival bleeding with brushing.
Complete biochemistry and hematology panel on presentation disclosed preserved renal and liver function, absence of leukocytosis, normal differential cell count, increased hemoglobin level of 20.2 mg/dL, and a normal platelet count of 145,000/muL. Other work-up included a negative HIV 4th- generation Ag/Ab test, non-detectable toxoplasma IgG and IgM serum antibodies, and negative blood cultures. Chest X-ray showed a dilated cardiac silhouette and mild pulmonary congestion. A repeat MRI of the head showed a ring-enhancing 3.7 x 3 x 3 cm mass within the right parietal lobe, with perilesional vasogenic edema (Fig. 1, Fig. 2). Lumbar puncture was not attempted due to lack of signs or symptoms of meningitis and potential risk of cerebral herniation. Transthoracic and transesophageal echocardiograms did not show any valvular vegetations.
The patient underwent emergent stereotactic-guided neurosurgical drainage, which yielded 100 cc of purulent material. Postoperatively, he was started on oral trimethoprim-sulfamethoxazole 800-160 mg every 12 h, intravenous metronidazole 500 mg every 12 h, and intravenous vancomycin 1 g every 8 h. Antibiotic management was challenging because of the patient's history of anaphylaxis to penicillin. Unfortunately, the patient was not desensitized to penicillin while under clinical observation, limiting choice of antibiotics. Cultures showed growth of Streptococcus intermedius, A. meyeri, and Parvimonas micra. The first two isolated organisms were susceptible to penicillin, ceftriaxone, vancomycin, clindamycin, and erythromycin. On subsequent complete dental evaluation, the patient was found to have a molar with an abscessed root, for which he underwent extraction. Once culture results were available, trimethoprim-sulfamethoxazole was discontinued and the patient was started on oral doxycycline 100 mg twice daily to cover A. meyeri. Doxycycline was chosen based on this organism's reported antibiotic susceptibility and need for optimal central nervous system (CNS) penetration. He was discharged to an acute rehabilitation facility with oral doxycycline and intravenous vancomycin and metronidazole. Although systemic availability of metronidazole has been shown to be similar following oral and intravenous administration, intravenous administration is often recommended for the treatment of life-threatening infections, at least for initial therapy. We also opted for intravenous metronidazole over oral for ease of administration.
The patient stopped vancomycin prematurely due to reported rash in week 4 which was deemed later to be an infusion-related Red Man's syndrome. An MRI 6 weeks into his antibiotic treatment showed interval signs of improvement with no evidence of abscess but with persistent hemorrhagic fluid, consistent with postoperative state. The patient was switched to oral doxycycline and oral metronidazole, and antiepileptics were stopped after electroencephalography was negative for seizure activity. Five months after his initial presentation, the patient underwent a second follow-up MRI brain examination that showed complete resolution of hemorrhagic fluid and no evidence of residual abscess. His clinical exam revealed stable residual left leg weakness. Metronidazole was stopped, and the patient was continued on doxycycline with a plan for 6 to 12 months based on published experience. | actinomyces, actinomyces meyeri, actinomycosis, brain abscess | Not supported with pagination yet | null |
PMC7585363_02 | Female | 30 | A 30-year-old woman was admitted to our emergency department with fever, cough, abdominal pain, bloating, inability to defecate, and melena. The patient had a history of Crohn's disease with suspected colitis. Abdominal distention was found in her physical examination. Laboratory results showed Hemoglobin level of 8.7 g/dL, Leucocyte count 9.75 x 109/L, Neutrophils 85.9%, Lymphocytes 7.9%, Neutrophils-Lymphocytes Ratio (NLR) 10.87, C-Reactive Protein (CRP) 171.67 mg/dL, and negative result of ANA test. Both Anti-SARS-CoV-2 IgG and IgM rapid tests showed non-reactive results. Chest X-Ray showed atypical bronchopneumonia (Fig. 2a) and chest CT scan showed bilateral pleural reaction with signs of pneumonia. Abdominal X-Ray showed ileus with small bowel obstruction suspected (Fig. 2b) and abdominal MSCT showed small intestine dilatation with sigmoid colon mass suspected. The patient was diagnosed small bowel ileus with bronchopneumonia. The patient underwent exploratory laparotomy with level 3 personal protective equipment. Intraoperative findings were multiple intestinal strictures with intestinal stenosis and ileal resection followed by end-to-end anastomosis using linear cutter was done (Fig. 2c). The COVID-19 PCR test with nasopharyngeal swab sample showed negative results and the pathologic finding showed intestinal tuberculosis. The patient was treated with streptomycin for 5 days after surgery and 6 months of anti-tuberculosis therapy were prescribed by the pulmonologist. | covid-19 pandemic, covid-19 symptoms, emergency surgery, gastrointestinal emergency case, respiratory symptoms | Not supported with pagination yet | null |
PMC7655243_01 | Female | 62 | A 62-year-old woman was initially presented as an outpatient ten years ago to the Department of Psychiatry at the University Hospital of Occupational and Environmental Health in Japan. She presented with mild mood swings, impulsive aggression, and reduced motivation and volition caused by a traumatic brain injury after a traffic accident. She had no previous history of substance abuse, hypertension, diabetes mellitus, or thyroid dysfunction. Magnetic resonance imaging revealed small hyperintensities in the left temporal and anterior frontal lobes, hippocampus, and amygdala. Based on the Wechsler Adult Intelligence Scale-Third Edition, the verbal intelligence quotient (IQ), performance IQ, and full IQ were 91, 96, and 92, respectively, which indicated normal intelligence. Her Mini-Mental State Examination score was 30/30, which indicated no cognitive impairment. She was often emotionally unstable; further, she was occasionally aggressive and cried after quarreling with her family members.
We initiated carbamazepine (CBZ) at an initial dose of 200 mg/day, which was increased to 600 mg/day. After four weeks, her mood swings gradually improved. She remained stable taking CBZ; however, she continued to present reduced motivation and volition. When the COVID-19 outbreak occurred in Japan, social media became inundated with COVID-19-related content. Consequently, she became concerned about COVID-19 and complained of multiple episodes of severe anxiety and shortness of breath that involved excessive sweating, body trembling, mouth dryness, and fear of death in public spaces. As a result, she could not go to the supermarket by herself due to excessive fear of contracting the illness. Further, her depressive mood worsened. Based on these symptoms, she was diagnosed with panic disorder comorbid with organic mood disorder and was prescribed sertraline (25 mg/day, which was increased to 100 mg/day) and 0.4 mg alprazolam as required. Her panic symptoms did not improve; consequently, vortioxetine was started and increased to 20 mg/day, while sertraline was tapered off. Four weeks after initiating vortioxetine, her symptoms of panic disorder and depressive mood, and reduced motivation were ameliorated. Further, her plasma level of CBZ was 6.4 mug/ml. Although the COVID-19 pandemic continues in Japan, she has remained well without any panic attacks while continuing vortioxetine treatment. The patient has been in remission of all mood symptoms and panic attacks. Written informed consent was obtained from the patient for publication of the present case report. | null | Not supported with pagination yet | null |
PMC3177409_01 | Male | 56 | A 56-year-old male presented with massive hemoptysis for 2 days. He had been experiencing low grade fever and recurrent episodes of streaky hemoptysis for 5 months. He was managed conservatively at a peripheral centre and was referred to our institute with ongoing episodes of hemoptysis amounting to 15-20 ml per episode. He had been previously treated for pulmonary tuberculosis about 18 years earlier. The hemogram, coagulogram, and routine blood biochemistry were within normal limits: hemoglobin of 8.2 g/dl, total leukocyte count of 7900/mm3 (70% neutrophils, 26% lymphocytes, 2% monocytes, 2% eosinophils) and erythrocyte sedimentation rate (ESR) of 65 mm in the first hour. Platelet count and coagulation profile were normal.
A chest radiograph showed fibrotic opacities and few thin-walled cavities in the left upper zone and an ill-defined nodular opacity in the right middle zone. MDCT angiography was done on a 64-channel multidetector scanner (Brilliance CT, Philips Medical systems, Cleveland, OH, USA) at our institution. The imaging parameters were: detector collimation, 64 x 0.625 mm; pitch, 1.108; gantry rotation time, 0.75 second; reconstructed section thickness, 0.9 mm; reconstruction interval, 0.45 mm; field of view, 350 mm; filter, sharp C; window center, 50; window width, 350; tube voltage, 120 kV; and planned tube current-time product, 250 mAs. High resolution lung window images were obtained with the following parameters: reconstruction section thickness, 0.8 mm; reconstruction interval, 0.4 mm; filter Y sharp; window center, -500, and window width, 1500. Through an intravenous antecubital catheter, 70 ml of nonionic contrast (Iomeron, 400 mg of iodine per ml; Bracco Pharmaceuticals, Milan, Italy) was injected by a power injector (Stellant; Medrad, Indianola, PA) with a flow rate of 4.5 ml/sec, followed by 40 ml saline chase at the rate of 4.0 ml/sec. The region of interest was placed in the descending thoracic aorta, and scanning was automatically initiated once a selected threshold (150 HU) was reached using a bolus tracking method.
MDCT revealed a necrotic nodular lesion and associated fibrotic components in the right middle lobe with areas of ground glass appearance and scattered tiny nodules in adjacent lung parenchyma. Small pocket of air was also present inside the necrotic lesion. MDCT angiography images showed multiple hypertrophied arteries inside the lesion with a small aneurysm (3 x 5 mm) [Figure 1a]. The right bronchial artery was mildly enlarged and could be traced to the parenchymal abnormality in the right middle lobe [Figure 1b]. MDCT also revealed fibrotic opacities in the left upper lobe with two small, thin-walled cavities and bronchiectatic changes in the left upper lobe [Figure 1c]. Based on clinical history and radiological findings, a diagnosis of reactivate tuberculosis with aneurysm formation was made.
The right bronchial artery was catheterized with a 5-F renal curve catheter. Selective arteriography confirmed the diagnosis of aneurysm of the right bronchial artery [Figure 2a]. Then, a microcatheter (Asahi Intec, Moriyama-ku, Nagoya-shi, Aichi 463-0024,Japan ) was advanced coaxially into the right bronchial artery and therapeutic embolization was performed with 300-500 mum polyvinyl alcohol (PVA) particles (Contour, Boston Scientific, Natick, MA 01760-1537, USA). Post-embolization angiogram showed occlusion of feeding vessels and aneurysm [Figure 2b]. Patient was put on antimycobacterial drugs and discharged 2 days later. On follow-up after 2 months, the patient had no recurrence of hemoptysis. | bronchial artery aneurysm, hemoptysis, multidetector computed tomographic angiography, therapeutic embolization, tuberculosis | Not supported with pagination yet | null |
PMC3764940_02 | Male | 26 | The patient was followed in our family cancer risk clinic because he belonged to a family with FAP. At the age of 16 colonic phenotype became evident and genetic testing was performed at age 18. Prophylactic proctocolectomy with J-ileal pouch and ileo-anal anastomosis was performed when he was 26 years old and he maintained sphincteric tone with good continence and about 4 bowel movements per day. Annual physical examination, laboratory screening and endoscopic evaluation of the pouch was performed as well as upper gastrointestinal endoscopy as dictated by the Spigelman score (last upper gastrointestinal endoscopy performed 3 months before symptoms).
One year before bloody diarrhea and weight loss were noted, multiple ulcers were seen on a routine pouch evaluation. At that time he was completely asymptomatic, hemoglobin levels were normal, and he mentioned a 7-day course of nonsteroidal anti-inflammatory drugs for dental pain. Biopsies showed subacute inflammation. Nonsteroidal anti-inflammatory drugs enteropathy was assumed at that time.
Investigation consisted of upper gastrointestinal endoscopy with findings of mild esophagitis and duodenal polyposis (Spigelman II), and pouch endoscopy showed no abnormal features. Stool cultures were negative. Small bowel capsule endoscopy showed multiple deep ulcers, some of them >2 cm long, and a hyperemic and congestive surrounding mucosa (fig. 1). Ileoscopy up to 60 cm from the anal verge was performed and multiple biopsies were taken from the ulcerated surface (fig. 2). Histology showed ulceration, regenerative changes, inflammation with lymphoid follicle formation and numerous polymorphonuclear cells infiltrating the submucosa. CD was assumed. MRI enterography showed no abnormal findings other than mucosal uptake in the jejunum and ileum.
We considered him to be a high-risk patient as he was a young smoker, with severe small bowel involvement from CD including the upper gastrointestinal tract (jejunum), already submitted to small bowel surgery (ileal pouch). After the mandatory viral serology tests and latent tuberculosis screening, 60 mg of oral prednisolone was started, with slow tapering during 12 weeks, while azathioprine was escalated up to 2.5 mg/kg. Iron supplementation was started. One year after diagnosis of CD the patient is symptom-free, has gained back 8 kg and has a normal hemoglobin level with replenished iron reserve. | capsule endoscopy, crohn's disease, familial adenomatous polyposis | Not supported with pagination yet | null |
PMC9197156_01 | Male | 25 | A 25-year-old right-handed male was admitted to our department with a chief complaint of swelling of the dorsal aspect of his right wrist for 3 years. There was no persistent pain in the right wrist. He had not suffered from severe trauma. The patient had undergone an ineffective superficial surgery of the right wrist 2 years earlier and no pathological specimen was sent. The wrist deformity had progressively worsened over the following 2 years. Physical examination showed a range of motion in the wrist of extension to 60 , flexion to 30 , ulnar deviation to 20 , and radial deviation to 0 . The fingers moved normally and functioned normally. Neurological examination of the right hand revealed diminished pain sensation. Apart from that, patients reported an obvious diminishing of pain when injured before. General laboratory tests did not reveal anything specific. X-ray examination confirmed bone resorption of the scaphoid (Figure 1A, B). Magnetic resonance imaging (MRI) examination showed hyperplasia of the surrounding tissue, but no damage to the articular surface of the radiolunate joint (Figure 1C, D). He was at that time diagnosed with synovitis and radiocarpal arthritis. We managed his disease with Four-Corner Arthrodesis and Synoviectomy to alleviate the damage of the joint and preserve motor function. At the time of surgery under general anesthesia, we observed synovial hyperplasia (Figure 2A), the collapse of the proximal half of the scaphoid, an intact radiolunate joint surface (Figure 2B), wear of the radialis carpal articular surface of radius (Figure 2C), and a deformity of dorsal intercalary segment instability (DISI). Following a limited intercarpal arthrodesis, the intraoperative radiograph showed improvement (Figure 2D). The wrist was fixed in a functional position, and the patient was then discharged.
The patient's right wrist became red, painful, progressively swollen, and immovable over the next 2 months. Imaging indicated increased carpal bone damage (Figure 3C-E). The white blood cell count was 8.81 x 109/L (reference values 4.00 x 109/L-10.00 x 109/L), and the proportion of neutrophils was 65.6% (reference values 50.0%-70.0%). Biopsy results showed no bacteria were cultured. Antinuclear antibody anti-cyclic citrullinated peptide antibodies and rheumatoid factor were negative. Results of acid-fast staining, T-SPOT.TB, and tuberculosis (TB) were both negative. Rheumatoid arthritis, TB arthritis, and infectious diseases were ruled out in this case. Because of the hypalgesia before surgery, a cervical MRI was conducted for further antidiastole, which revealed Chiari II syringomyelia (Figure 4A, B). The patient was eventually diagnosed with destructive NA (syringomyelia), ut refused to undergo carpal and spinal surgery. After 2 months of conservative treatment, the right wrist spontaneously and completely fused and the pain disappeared (Figure 3F, G). During the 1-year follow-up, there was no acute change in the condition (Figure 3H-K). The patient was generally satisfied with the outcomes of the treatment. | case report, limited intercarpal arthrodesis, neuropathic arthropathy, spontaneous total fusion, wrist | Not supported with pagination yet | null |
PMC7194471_01 | Male | 29 | We are reporting here the case of a 29 year old male Caucasian professional football athlete who suffered a sport-related ankle sprain in April 2019. The injury occurred during a regular exercise session on artificial turf as an inversion sprain accompanied by plantar flexion. The patient was immediately evaluated by a sports medicine specialist who confirmed the category and the degree of injury (grade II ankle sprain) by physical examination. The patient was an apparently healthy young men (age 29 years, weight 77.0 kg, height 184.0 cm, professional experience 11 years), with no history of ankle sprain (or other lower extremity injuries) in the past 6 months, and no cardiometabolic or other musculoskeletal disorders. Written informed consent was obtained from the patient in accordance with the Declaration of Helsinki, and study protocol approved by the local IRB at the FSPE Applied Bioenergetics Lab at the University of Novi Sad (A14-2019).
At the initial examination immediately after the injury, right ankle was painful, swollen and warm, and had increased laxity on testing ( Figure 1, Panel a). Self-completed visual analog scale (VAS) score for pain was 50 points (moderate pain). Figure-of-eight method of measuring ankle joint swelling at the injured ankle revealed 56.5 cm, with weight-bearing lunge test (WBLT) showing 43.1 mm. The patient demonstrated a diminished ability to bear weight.
Hydrotherapy with super-saturated hydrogen-rich water was used as an exclusive treatment (besides rest) with the main aim to reduce symptoms and signs of acute ankle sprain, and it was hoped to speed up the acute recovery. Super-saturated hydrogen-rich water was produced by putting a magnesium-producing formulation (10 g) into a 3-L stationary whirlpool with tap water of neutral temperature (20 C). Hydrogen was produced by a following reaction: Mg + H 2O H 2 + Mg(OH) 2, with concentration of hydrogen in a whirlpool ~ 8 ppm. The intervention was provided by HRW Natural Health Products Inc. (catalogue number 6-27843; New Westminster, BC, Canada). Throughout the 24 hours after the ankle sprain, the participant received six 30-min ankle baths (e.g. one hydrotherapy every 4 hours), with the first session given immediately after an initial examination (~ 60 min after the injury). During each session, the foot and ankle of injured leg were immersed in a stationary whirlpool. All hydrotherapies were formulated and supervised by a health care professional.
At the 24-h follow-up examination ( Figure 1, Panel b), VAS score for pain dropped to 20 points (mild pain), with ankle circumference decreased to 54.9 cm; WBLT improved to 55.0 mm. The patient reported no side effects of hydrogen intervention (e.g. pain, cramps, tingling, discoloration of skin, burning, itching, rash), as evaluated with open-ended questionnaire administered at the end of each session of hydrotherapy, and at 24-h follow-up. | ankle sprain, hydrotherapy, molecular hydrogen | Not supported with pagination yet | null |
PMC9233223_01 | Male | 37 | A 37-year-old South Asian male was admitted to our hospital with dysuria and urine retention for one day. He has a history of stage 3 chronic kidney disease and bilateral obstructive uropathy due to kidney stones which required multiple invasive urological interventions three months ago prior to this presentation. Additionally, he was diagnosed with painful bladder syndrome requiring regular intravesical injections; the last one was four weeks before this presentation. On the following day of admission, he developed fever (temperature of 38.7 C), and the laboratory investigations revealed white blood cells (WBC) of 7.1 x 103/uL (normal range:4-10), C-reactive protein (CRP) of 93.7 mg/L(elevated), creatinine of 179 umol/L (within his baseline range), and urine WBC of 242/ hpf. Blood and urine cultures were negative. The urinary tract computed tomography revealed bilateral hydroureteronephrosis with no detectable ureteric or bladder stones (Fig. 1). Despite being on ertapenem (accordingly to his previous culture and sensitivity) for more than three days, he still had worsening urinary symptoms and spiking temperature. Repeated urine analysis revealed the presence of pus cells with negative cultures again. Accordingly, given the presence of recurrent sterile pyuria and his history of extensive urological interventions, a work-up for a mycobacterial UTI was performed. The Acid-Fast Bacilli (AFB) smears of the urine sample were negative. Cystoscopy with bladder biopsy was done, which revealed non-necrotizing granulomatous cystitis (Fig. 2). Two weeks later, urine culture(MTB cultures using both solid media, Middlebrook 7H11, and liquid media using BACTEC MGIT 960) grew Mycobacterium abscessus complex (MABC), which is later identified through real time PCR as Mycobacterium abscessus subspecies abscessus.
Subsequently, the patient was commenced empirically on a combination of meropenem (1 gm every 12 h), amikacin (433 mg once daily), ciprofloxacin (400 mg intravenous every 8 h), and clarithromycin (500 mg orally every 12 h). However, his creatinine worsened (increased from 170 to 249) due to amikacin nephrotoxicity; hence, amikacin was replaced by intravenous linezolid (600 mg every 12 h). However, two weeks after starting linezolid, the patient developed significant thrombocytopenia (platelet count dropped to 54), and subsequently, linezolid was substituted with doxycycline (100 mg oral every 12 h). The final urine culture and drugs susceptibility showed that the organism is resistant to doxycycline and ciprofloxacin and sensitive to tigecycline and clofazimine (Table 1). Therefore, he was kept on meropenem, tigecycline, clofazimine, and clarithromycin for two months, then meropenem and tigecycline stopped, and he was continued on clofazimine and clarithromycin. His monthly repeated urine mycobacterial cultures showed no growth, his HIV test was negative, and no abnormalities were detected in the chest- X-ray. At eight months follow-up from starting treatment, the patient was afebrile and asymptomatic, tolerating oral clofazimine and clarithromycin with persistent negative urine culture for mycobacterium abscessus. He was planned for 12 months of therapy from the first negative urine cultures. | amikacin, chronic kidney disease, clarithromycin, genitourinary infections, mycobacterium abscessus, nontuberculous mycobacteria | Not supported with pagination yet | null |
PMC9485662_01 | Male | 57 | A 57-year-old man was admitted because of abdominal distension, anorexia and constipation for 5 weeks, chest pain for 1 week, and fever for 1 day on 16 April 2020. On 8 March 2020, the patient developed abdominal distension, anorexia, constipation, and decreased anus exhaust, and was given drugs to promote gastrointestinal motility but with no improvement. On 9 April 2020, the patient was accidentally hit by a wrench on the left side of the chest at work, and it was accompanied by chest pain. The chest CT at the local hospital revealed Wegener's granulomatosis, which did not exclude the possibility of tuberculosis, and no further diagnosis or treatment were performed. On 15 April 2020, the patient developed chills and fever with a body temperature of 39C during his visit to our outpatient department. The blood routine showed a WBC of 7.33 x 109/L, hemoglobin of 98 g/L, a neutrophil ratio of 87.1%, and a C-reactive protein of 119.72 mg/L. The results of plain chest and abdomen films showed multiple lesions in bilateral lungs, with the nature to be determined, and enterostasis. Then, the patient was admitted for further treatment.
The patient had chronic viral hepatitis B and type 2 diabetes mellitus, and was given entecavir 0.5 mg qd for anti-hepatitis B virus treatment. He was diagnosed with hepatitis B virus-associated membranous nephropathy in 2019 and had received high-dose hormone therapy (Medrol 48 mg qd) for 2 months before the onset of the disease. His lymphocytes were decreased: total T lymphocytes 427 cells/mul, helper T cells 210 cells/mul, and suppressor T cells 209 cells/mul. Two months ago, the patient was given methylprednisolone 48 mg qd because there was no improvement in urine protein, and the dose was reduced to 44 mg qd 2 days before the admission. The patient was engaged in furniture manufacturing and works in a dusty environment.
On admission, his body temperature was 39.5 C, the respiratory rate was 22 breaths per minute, and his consciousness was clear. There was no yellowing of the whole body skin mucosa, rash, or subcutaneous hemorrhage. Liver palm was notable but without obvious spider nevus. The oral cavity and pharynx were found to have a bean curd-like attachment, and the tongue was thick with white spots. The patient's breath sounds were weak bilaterally, with the left lung more pronounced, and there was pressure pain around the umbilicus. The cardiovascular system and nervous systems and the limbs were unremarkable.
The laboratory tests showed interleukin-6 of 137.2 pg/ml, serum ferritin of 1,642.3 ng/ml, and an erythrocyte sedimentation rate of 83 mm/h. The T-lymphocyte subsets shown by flow cytometry indicated an absolute value of total T cells of 427 cells/mul, an absolute value of helper T cells (Th) of 210 cells/mul, and an absolute value of suppressor T cells (Ts) of 209 cells/mul. Seven items of immune functions demonstrated a total complement hemolytic activity of 68 IU/L and immunoglobulin G of 6.29 g/L. For liver function, globulin was 19.3 g/L and albumin was 24.6 g/L. Glycosylated hemoglobin was 10.7%. The tuberculosis immune spot test was negative. Fungal D-glucan was 745 ng/L. The fungal culture with throat wipes detected Candida albicans. The routine urine test was positive for urine protein and urine glucose.
After the admission, the patient was given fluconazole injection 200 mg qd, latamoxef 1 g q12 h for anti-infection, entecavir 0.5 mg qd for anti-hepatitis B virus, methylprednisolone 44 mg qd for anti-hepatitis B virus, and blood glucose control, urine protein reduction, kidney protection, and other treatments. On the 2nd day of admission, the patient's temperature returned to normal, and the re-examination showed a high-sensitivity C-reactive protein of 20.98 mg/L and procalcitonin <0.05 ng/ml. Since the pathogens of pulmonary infection were unknown, on the 7th day of admission, bronchofiberscopy was performed and bronchoalveolar lavage fluid (BALF) was collected for pathogen detection (culture + tuberculosis gene probe). The patient presented with a postoperative transient temperature of 38.5 C with chills and was considered to have an acute upper respiratory tract infection. After antiviral treatment with oseltamivir 75 mg bid, the body temperature returned to normal on the same day. Sputum specimens and BALF specimens were sent several times for sputum smears and cultures, and no M. tuberculosis was found in the smears or cultures. However, the BALF specimens were positive for M. tuberculosis gene probes A, B, C, and E and negative for rifampicin resistance mutation. A. fumigatus was cultured from the bronchoalveolar lavage fluid, and the preliminary diagnosis was pulmonary tuberculosis and pulmonary Aspergillus infection. Glucocorticoids were discontinued on the 8th day of admission, and fluconazole and latamoxef were discontinued. The anti-tuberculosis regimen was changed to isoniazid 0.3 g qd, ethambutol 1 g qd, pyrazinamide 1 g qd, and levofloxacin 0.4 g qd, and the antifungal therapy was changed to Voriconazole 200 mg q12 h.
On the 10th day of admission, the patient again developed hyperthermia, with a temperature of 39.4 C, accompanied by chills, left-sided chest pain with blood in the sputum, and shortness of breath. The repeat examination showed high-sensitivity a C-reactive protein of 98.58 mg/L, procalcitonin of 0.09 ng/ml, and a decreased oxygenation index compared to before. The repeat chest CT showed multiple infectious lesions, some nodules with cavities in both upper lungs, a small amount of pleural and pericardial effusion, and progressive lesions compared with the CT film from another hospital (Figure 1). Considering that the fever was caused by aggravation of the pulmonary infection, levofloxacin was changed to moxifloxacin hydrochloride in sodium chloride injection 0.4 g qd. Fever peak decreased slightly, but the body temperature did not decrease to normal. On the 13th day of admission, the patient had a high fever again, with the highest body temperature of 39.5 C. The infection indicators continued to rise on recheck, with a high-sensitivity C-reactive protein of 123.54 mg/L and procalcitonin of 0.11 ng/ml.
BALF samples were submitted for PACEseq metagenomic next-generation sequencing (mNGS) (Hugobiotech, Beijing, China), and A. fumigatus (227 reads), N. nova (148 reads), M. tuberculosis (1 read), human alphaherpesvirus 1 (39 reads), and human cytomegalovirus (11 reads) were detected (Figure 2). Briefly, for the mNGS method, the collected BALF specimen was centrifuged at 5,000 g and at room temperature for 10 min, and DNA was extracted from the supernatant using the TIANamp Micro DNA Kit (DP316, Tiangen Biotech). Sequencing libraries were constructed with the QIAseq Ultralow Input Library Kit (Illumina). Qualified libraries with different tags were pooled together and amplified and then sequenced with a Nextseq550 system (Illumina) for 150 cycles. Kytococcus sedentarius (51 reads), Streptococcus gordonii (36 reads), Rothia dentocariosa (82 reads), Nocardia mikamii (10 reads), Streptococcus mitis (21 reads), Lactobacillus salivarius (25 reads), and Streptococcus pseudopneumoniae (43 reads) were also detected by the mNGS but were considered as oral colonizing microorganisms and were not considered as pathogenic microorganisms.
A needle biopsy of the left upper lung tissue was also performed, and the mNGS of the lung tissue revealed N. nova (92 reads) and human cytomegalovirus (2 reads) (Figure 2). The serum viral examination was CMV-IgG positive and CMV DNA-positive. Herpes simplex virus type I IgG was positive and herpes simplex virus type I IgM was negative. The histopathological examination of the lungs revealed purulent inflammation with fibrinous inflammation (Figure 3). Combined with the characteristics of imaging changes, mNGS results of BALF and lung tissues, the patient was considered to have a multi-pathogen infection (N. nova, M. tuberculosis, A. fumigatus, and cytomegalovirus). The pulmonary imaging features of this patient were predominantly cavernous and not consistent with viral pneumonia manifestation features, so respiratory infection caused by human alphaherpesvirus 1 was not considered.
The treatment regimen was then adjusted to co-trimoxazole 3 tablets tid and imipenem and cilastatin sodium injection 1 g, q8 h for the treatment of N. nova, and ganciclovir 0.25 g, q12 h for the treatment of cytomegalovirus. The anti-tuberculosis and Aspergillus treatments were also continued. The fever peak was decreased, and his chest pain was relieved, with normal temperature on the 17th day of admission. The dynamic reexamination revealed that the infection indicators had decreased gradually. On day 24 of admission, the repeat chest CT showed improvement of the pulmonary infection (Figure 4), CMV DNA was negative, and "ganciclovir" was discontinued. On day 44 of admission, the patient recovered and was discharged. The patient continued to receive the anti-tuberculosis and antifungal treatments with Voriconazole 200 mg q12 h and sulfonamide Tablets 3 tablets tid for N. nova in the outpatient department. A review of the chest CT at 1 and 3 months after discharge showed that the lesion was gradually absorbed. | nocardia nova, metagenomic next-generation sequencing (mngs), mixed infection, pathogen diagnosis, pulmonary infection | Not supported with pagination yet | null |
PMC9981961_01 | Male | 64 | The reporting of this study conforms to CARE guidelines. In Dec. 3, 2021, a 64-year-old man with a solid space-occupying lesion that measured 25 x 36 mm in the inferior pole of the left kidney by Doppler ultrasound during physical examination one month prior. The body mass index (BMI) was 22.19 kg/m2. Meanwhile, the patient was generally well, was afebrile, and did not experience low back pain or discomfort, frequent urination, urgency, painful urination and gross haematuria. Additionally, the patient denied gastrointestinal symptoms such as abdominal pain and distention, nausea and vomiting. The patient had a 6-year special history of hypertension, and his blood pressure was well controlled by regular oral antihypertensive drugs. During hospitalisation, his maximum monitored blood pressure (BP) was 135/97 mmHg, and his monitored heart rate ranged from 72 to 90 bpm. The patient denied any history of other medications, diabetes, abdominal surgery or trauma, abdominal tuberculosis, peritoneal dialysis, autoimmune disease, or chemotherapy. Preoperative blood tests and comprehensive metabolic panel suggested no abnormalities. Renal Doppler ultrasound showed a solid space-occupying lesion in the left kidney, which required further evaluation. Computer tomography urography (CTU) and angiography (CTA) showed that the stomach and spleen were located in the right abdominal cavity, while the right hepatic lobe, gallbladder and inferior vena cava were at the left side of his abdomen (Figures 1A-E), the bilateral kidneys were normal in size and shape, but a 24 x 35 mm isodense mass protruded from the outline of the left kidney (Figures 1B-E). On contrast-enhanced computed tomography (CT) scan, the mass was strongly enhanced in the arterial phase (Figure 1C), and the enhancement pattern was attenuated during the venous phase (Figure 1D). There was a 31 x 40 mm non-enhancing hypodense nodule and calcification of the wall in the right renal. Additionally, the left renal artery was supplied by one renal artery and one accessory renal artery (Figure 1E). Effusion or lymphadenopathy in the abdominopelvic cavity was not noted. Based on the above findings, the patient was confirmed as having SIT, for the space-occupying lesion in the left kidney, clear cell RCC (ccRCC) was considered, the lesion in the right kidney was probably cystic. Cardiac Doppler ultrasound demonstrated decreased diastolic function and normal systolic function of the left ventricle in the transposed heart. The estimated glomerular filtration rates (eGFR) were 29.76 and 28.8 ml/min for the left and right kidneys, respectively. Chest CT showed no space-occupying lesions or evident abnormalities. Before surgery, the patient was diagnosed with left RCC, SIT, right renal cyst and hypertension. We diagnosed our patient as having a cT1aN0M0 left RCC, and the RENAL score was 7x. With PN being the preferred treatment approach, left RALPN was performed after obtaining informed consent.
Surgery was performed under general anaesthesia with the patient being placed in a supine position and angled at 70 on the unaffected side. A 1.0 cm incision was created at the medial umbilical edge for insertion of a Veress needle and induction of CO2 pneumoperitoneum that was maintained at 15 mmHg. A laparoscope was then inserted to observe the abdominal cavity, adhesions were observed between the entire colon and the anterior abdominal wall, particularly between the intestines (Figures 2A,B). Based on these findings, abdominal cocoon was diagnosed. Under direct laparoscopy, two 8-mm robotic ports were respectively placed in adhesion-free areas in the intestine 4 cm from the anterior superior iliac spine and under the costal margin (Figure 3A), while a 12-mm assistant port was inserted 5 cm under the umbilicus at the midline (Figure 3A). When the robotic laparoscopy system was ready, adhesions between the colon and the anterior abdominal wall were removed (Figure 2B-D). The transposed organs, including the liver, spleen, stomach and colon, were then noted (Figure 2C,D). The inferior vena cava was located on the left side (Figure 2E-H). A protruding tumour (Figure 2G) was found in the left kidney, three arterial branches were dissected (including one from the abdominal aorta to the lower pole of the kidney, and two from the main renal artery to the middle and lower poles of the kidney) (Figure 2F). The surgery was uneventful, and the tumour was resected successfully while preserving the tumour capsule (Figure 2I). The operation time was 180 min, which included 23 min of warm ischemia time. The intraoperative blood loss was 200 ml. A 23 x 36 mm specimen was removed from the left kidney and sectioned to confirm tumour capsule integrity (Figure 3B). Pathology revealed pT1aN0M0 Fuhrman Grade I ccRCC, which did not involve the surgical margins (Figure 4A,B). No intestinal injury or any other complication occurred in the intraoperative or postoperative. The patient was satisfied with the treatment. The patient was discharged at postoperative on day 7. Postoperatively, the patient was followed up for 10 months, and no recurrence, secondary infection, or intestinal obstruction was detected. | abdominal cocoon, case report, partial nephrectomy, renal cell carcinoma, robot-assisted laparoscopic, situs inversus totalis | Not supported with pagination yet | null |
PMC9577070_01 | Male | 75 | A 75-year-old male patient from Yongjia county (Zhejiang province, China) visited our hospital [i.e., Wenzhou Central Hospital (WCH)/The Second Affiliated Hospital of Shanghai University] on 16 November 2021 (defined as day 0) with the manifestation of fever accompanied by expectoration for 6 days and diarrhea for 5 days.
The patient had visited a local clinic and received oral medication (the detail was unknown) 6 days ago due to fever and paroxysmal cough with yellow sticky phlegm. The patient had a maximum body temperature of 39.0 C and felt no chills then (i.e., 6 days ago). One day later, the patient started to have an episode of watery diarrhea with a stool frequency of four to five times per day, which is accompanied by pains in bilateral thighs and shanks. He then visited the Second Affiliated Hospital of Wenzhou Medical University on the same day (i.e., 5 days ago), where he was administered with piperacillin sodium and tazobactam sodium [4.5 g, intravenous (I.V.) infusion every 8 h (quaque octa hora, q8h)], levofloxacin [0.5 g, I.V. infusion one a day (quaque die, qd)], and fluid infusion.
A chest CT on day 0 showed binary pulmonary infection, which was in suspicion of pulmonary tuberculosis (PTB) ( Figure 1A ). Given the pulmonary infection and acute renal failure, the patient was admitted to our hospital the next day and subsequently transferred to the infectious intensive care unit (ICU) of our hospital for further diagnosis and treatment.
On admission, the patient had an ear temperature of 37.2 C, a pulse rate of 83 beats per minute, a blood pressure of 100/54 mmHg, and a respiratory rate of 18 breaths per minute. At that time, he was conscious and mentally normal. Physical examination showed that both of his pupils were round and equal in size (3 mm in diameter). There was no jaundice, scleral icterus, spider angioma, or palmer erythema observed. The patient's neck was supple, trachea was at the midline of the neck, and the patient had no jugular vein engorgement. Abnormal breathing sounds was auscultated in bilateral lungs of the patient, and occasional moist rale in the right lower lobe. In addition, the patient had normal heart rhythm and no pathological murmurs of valves on auscultation. His belly was soft, and there was no (rebound) tenderness as revealed by palpation. The liver and spleen were not palpable. There was no leg edema. The bilateral pathological reflexes were negative.
The result of initial laboratory examination (day 1) was as follows: white blood cell count (WBC), 11.43 x 109 cells/L; neutrophils % (neut. %), 0.924%; hemoglobin (HB), 88 g/L; platelets (PLT), 86 x 109 cells/L; C-reactive protein (CRP), 165.53 mg/L; total protein, 52.8 g/L; albumin, 26.6 g/L; bilirubin, 22.1 mumol/L; and creatinine, 464 mumol/L ( Table 1 ).
Anti-infectious treatment was empirically administered with sulperazone (2.0 g, I.V. infusion, q8h) and moxifloxacin (0.4 g, I.V. infusion, qd) on day 1, combined with supportive care for relieving cough, reducing sputum, and regulating intestinal flora and fluid infusion. The patient still manifested with persistent fever, chest distress, and tachypnea. Oxygen was then supplied at a rate of 6 L/min using an oxygen mask to maintain an oxygen saturation of 95%. The patient had less urine and progressively elevated creatinine. He was then given methylprednisolone [40 mg, I.V. infusion bis in die (bid)] on day 2 to enhance the anti-inflammatory effect and reduce pulmonary exudation. Continuous renal replacement therapy (CRRT) was simultaneously applied. On day 3, the patient produced blood-tinged sputum. Xpert MTB RIF using sputum identified the presence of rifampicin-sensitive Mycobacterium tuberculosis complex (MTBC) (data not shown). In association with the chest CT result ( Figure 1A ), the diagnosis of PTB was confirmed. The therapeutic strategy was then altered to rifampicin [0.45 g, by mouth (per os, P.O.) every morning (quaque mane, qm)], isoniazid tablets (0.3 g, P.O., qm), ethambutol tablet [0.75 g, P.O., ter in week (tiw)], and pyrazinamide tablets (1.5 g, P.O., tiw). After CRRT, the level of serum creatinine decreased during day 2 and day 3. However, the patient became restless and delirious at the night of day 3. Since he was unable to communicate with, tolerate being in bed, or cooperate to the treatment, CRRT was forced to be terminated and sedation was applied.
On day 4, lumbar puncture was conducted with a CSF opening pressure of 50 mmH2O. CSF examination was as follows: WBC, 2 x 106 cells/L; protein, 0.30 g/L; chloride, 127 mmol/L; and glucose, 5.2 mmol/L. There was neither Cryptococcus neoformans nor MTBC (via Xpert MTB RIF) detected. The samples of CSF, urine, and plasma prepared on day 4 were subjected to mNGS, by which the DNA sequences of L. interrogans (without MTBC) were detected with read numbers of 4, 9, and 2, respectively (reported on day 6; Table 2 , Supplementary Figures 1A-C ). This was in accordance with the positive screening for Leptospira in blood samples of the patient that were collected on day 3 and detected using the Serion ELISA classic Leptospira immunoglobulin G (IgG) kit by the Wenzhou Center for Disease Control and Prevention (reported on day 4 after samples being sent for mNGS). Therefore, the diagnosis of leptospirosis was verified. In combination with the heightened inflammation in bilateral lungs shown by the chest CT screen on day 4 ( Figure 1B ) as well as mental changes of the patient developed during the administration of sulperazone and moxifloxacin, the Jarisch-Herxheimer reaction (JHR) and leptospirosis-induced encephalopathy were of high suspicion. Accordingly, the dosage of methylprednisolone was increased to 80 mg from 40 mg, I.V., bid; sulperazone and moxifloxacin were replaced with penicillin (800,000 IU, I.V., q8h; the initial dose was 400,000 IU) from day 4. On day 6, the patient's consciousness improved, so the sedation was gradually terminated (see Table 1 for detailed laboratory tests). The chest CT of day 6 showed decreased infection foci and less amount of pleural effusion in the lung, in comparison to that of day 4 ( Figures 1B, C ). To further confirm the result of Xpert MTB RIF and CT, the sputum of the patient was also prepared for mNGS on day 6, from which the DNA sequences corresponding to MTBC (without L. interrogans) were detected with a read number of 4 (reported on day 8; Table 2 , Supplementary Figure 1D ). The mNGS result of sputum was consistent with the Xpert MTB RIF result of day 3. On day 13, patchy shadows with high density were roughly absorbed as revealed by chest CT ( Figure 1D ); thus, the patient was transferred to the general ward of the infectious disease department for subsequent treatment. The detailed clinical course of the patient during hospitalization is shown in Figure 2 .
After sequential operations, including the sample preparation of microbial cell wall disruption via bead beating (for CSF and urine, not for plasma), DNA extraction and library construction (PCR-free) using an NGS Automatic Library Preparation System (Hangzhou Matridx Biotechnology Co., Ltd., Zhejiang, China), NGS on an Illumina NextSeq 550Dx (single end, 50 bp), and the data processing of removing short reads (<35 bp), low-quality and low-complexity reads, and high-quality sequencing data were generated. The generated data were then separately aligned to a human-specific database constructed from Homo sapiens sequences in NCBI nucleotide (nt) databases (for eliminating human sequences) using bowtie2 v2.3.5.1, and a manual-curated microbial genome database for taxonomy classification using kraken2 (confidence = 0.5) and bowtie2 v2.3.5.1. The microbial genome database contained 11,704 viral genome sequences, 11,162 bacterial genome sequences, 229 parasite genomes, and 1,324 fungal genomes relevant to human infectivity. Moreover, the reads classified to L. interrogans or MTBC were subsequently aligned to a relevant microbial genome (i.e., L. interrogans or MTBC) using BLASTN v2.10.1+ for further validation ( Supplementary Figure 1D ). | co-infection, early diagnosis, leptospirosis, mngs, pulmonary tuberculosis (ptb) | Not supported with pagination yet | null |
PMC6232149_01 | Male | 21 | A 21-year-old Chinese male who was undergoing magnetic resonance imaging (MRI) of the internal auditory meatus (IAM) for investigation of asymmetrical mild-moderate low frequency sensorineural hearing loss diagnosed since childhood was incidentally found to have a large sellar and suprasellar mass. Subsequent MRI of the pituitary fossa indicated it to be likely a hypothalamic hamartoma. He was seen by an endocrinologist for further evaluation of his pituitary hormones. Clinically, the patient was euthyroid, and there was no postural hypotension elicited. Testicular size was normal at 20 ml bilaterally, and secondary sexual characteristics were present. On biochemical evaluation, other than a borderline peak serum cortisol response of 490 nmol/l following a short Synacthen test (normal response: >=500 nmol/l), the rest of the pituitary function was well intact. Based on a suspicion of PHS, the patient was referred for a genetics assessment.
Detailed clinical (Table 1) and family (Fig. 1a) histories were taken. The patient was born to nonconsanguineous parents following an uneventful pregnancy with normal spontaneous vaginal delivery at full-term. His mother reported no teratogen exposure during pregnancy. At birth, he was hypotonic and weighed 3800 g (81st centile). He presented with bilateral polydactyly: left hand mesoaxial and postaxial polydactyly (3rd-4th metacarpal syndactyly and bifurcation of 5th metacarpus) and right hand mesoaxial and postaxial polydactyly (3rd-4th metacarpal syndactyly and trifurcation of 5th metacarpus). He underwent several corrective surgeries before 2 years of age. At 6 months, he was noted to have episodes of limb jerking for a period of 2 weeks and underwent an electroencephalogram (EEG) and pediatrician review, which detected no abnormality (no further recurrence was noted). Delayed speech and motor development was noted at age 2 years, and he attended speech, language and occupational therapy at a tertiary children's hospital. His milestones were delayed: he walked at 24 months; he acquired day- and night-time bladder control at 30 and 45 months, respectively; he acquired bowel control at 30 months; he used single words at 30 months, and he used his first phrases at 42 months. At age 11.5 years, he was assessed to have good cognitive ability but displayed difficulties with social interaction, communication, emotional regulation and motor skills (using WISC-IV, ADI-R, and ADOS). He had precocious puberty at age 8 years and ceased growing at approximately age 13 years. His current height is 163.0 cm (significantly shorter than his sibling), and his weight is 52.7 kg. He has a history of prognathism and underwent jaw realignment surgery at age 14 years. The patient reported recent episodes of intense anxiety accompanied by an inability to move his upper limbs and shaking of lower limbs, which lasted approximately 15-30 min. Subsequent EEG and neurology assessments reported no abnormalities. He is asymptomatic for bifid epiglottis; renal ultrasound was normal; and anal and genitourinary anomalies were absent in this patient. His occipital frontal circumference is 56.0 cm, and he has low-set, prominent ears.
He has no family history of PHS or PHS-associated manifestations (Fig. 1a). His father was diagnosed with a giant cell tumor of his left distal radius at age 33 years (verified by medical report).
The patient's peripheral blood DNA was analyzed using the Syndromic Macrocephaly/Overgrowth Panel by the GeneDx, Inc. laboratory, which included 29 genes (AKT3, BRWD3, CCND2, CHD8, CUL4B, DNMT3A, EZH2, GLI3, GPC3, HEPACAM, HERC1, MED12, MTOR, NFIA, NFIX, NSD1, OFD1, PHF6, PIK3CA, PIK3R2, PPP2R5D, PTCH1, PTEN, RAB39B, RNF135, SETD2, SNX14, TBC1D7, UPF3B). Although GLI3 testing alone would have been sufficient in this case, many of the phenotypes associated with these genes have significant overlap. The complete coding regions and splice site junctions of the included genes were enriched and sequenced with paired-end reads on an Illumina platform. Copy number variant (CNV) calling was included. The reads were assembled and aligned to reference sequences (NCBI RefSeq transcripts and human genome build GRCh37/UCSC hg19). A novel heterozygous nonsense pathogenic variant in GLI3, NM_000168.5:c.2071C>T p.(Gln691*), was detected (Fig. 1b). In-house Sanger sequencing of peripheral blood DNA from his parents and brother did not detect the GLI3 variant; therefore, his mutation is likely to be de novo (Fig. 1b), although germline mosaicism cannot be excluded and has been previously reported in PHS. Additionally, he was found to be hemizygous for a variant of uncertain significance (VUS) in MED12, NM_005120.2:c.1031C>A p.(Thr344Asn), located on the X chromosome. His mother was heterozygous and brother hemizygous for the MED12 VUS, and his father was excluded as a carrier. His brother had no MED12-associated manifestations and had normal intelligence, suggesting the variant is less likely to adversely affect MED12 function. Autosomal dominant inheritance and reproductive options, including prenatal diagnosis and preimplantation genetic diagnosis, were discussed with the patient. He will continue to follow-up regularly with endocrinology and neurology. Written research consent was obtained from all four family members.
There have been more than 40 GLI3 pathogenic variants reported to be associated with either PHS or sub-PHS, where a diagnosis is suspected but does not meet the diagnostic criteria (Fig. 1c). While the majority are frameshift and nonsense mutations, one splicing variant has been reported. Approximately a quarter of all known PHS cases have been caused by a de novo pathogenic variant. The GLI3 variant detected in our patient falls between the zinc-finger domain and the proteolytic cleavage site. It is located within the middle third of the GLI3 gene where all PHS-causing pathogenic variants have been identified, providing further support for the well-established genotype-phenotype correlation.
In this report, we describe a case of PHS caused by a novel GLI3 nonsense variant that was not diagnosed until adulthood, despite multiple points of contact with pediatric and developmental health services throughout the patient's childhood. Although the patient presented with several features at birth and during early childhood that would warrant a genetics assessment, he was not referred. Only a handful of PHS cases diagnosed during adulthood have been reported. The majority are born with polydactyly, but a diagnosis of PHS is only suspected following a subsequent event, such as the presence of epileptic seizures, precocious puberty, hypothalamic hamartoma, or the birth of offspring with a more severe phenotype. The diagnosis of precocious puberty in our patient, in combination with bilateral polydactyly, should have raised the suspicion of PHS. More than a decade passed before a diagnosis of PHS was made, following the incidental finding of the hypothalamic hamartoma. This case adds to the literature of PHS diagnosed in adulthood, which together serve to bring attention to the missed opportunities for genetic testing and subsequent diagnosis. Earlier diagnosis has the potential to alleviate the burden on patients and their families when there is a lack of a definitive reason for their medical history. This is especially important for PHS manifestations, where early detection and management can help improve outcomes, such as endocrine and developmental manifestations. Further education is required to raise awareness among health professionals who may encounter individuals with PHS at early stages of life, such as surgeons and pediatricians.
The relevant data from this Data Report are hosted at the Human Genome Variation Database at 10.6084/m9.figshare.hgv.2402. | null | Not supported with pagination yet | null |
PMC9887664_01 | Female | 32 | A 32-year-old female came with a chief complaint of swelling over the right side of the back since last year. It was gradual in onset, and there was a progressive increase in the size of the swelling. The patient complained of pain over the swelling. She had a history of cyst excision done four years back from the same site.
On local examination, a palpable lump of size 3 cm x 3 cm was present over the right side of the back (Figure 1). The swelling was firm, non-tender, and non-mobile. There were no areas of redness over the swelling. There was no local increase in temperature or any skin discoloration around the swelling. Systemic examination revealed no abnormalities.
Timeline of the current episode
The patient had swelling on the right side of the back for one year. Swelling gradually increased in size, involved the skin over the back, and caused pain and discomfort to the patient during the previous week. The patient had a similar complaint of cystic swelling over the same site four years back, which she had got excised. The patient exhibited generalized weakness. There was no history of discharge from the swelling. The patient does not have diabetes mellitus, asthma, tuberculosis (TB), hypertension, or any other known diseases.
Diagnostic assessment
The USG local region revealed a well-defined hypo-echoic lesion of size 3.8 cm x 2.1 cm x 3.5 cm in the subcutaneous area in the right lumbar region. It showed posterior acoustic enhancement and multiple septa within. Color Doppler imaging revealed a significant vascularity. The patient was provisionally diagnosed with peripheral nerve sheath tumor. USG-guided fine needle aspiration cytology (FNAC) was performed.
Operative procedure
Wide local excision of the tumor was performed under general anesthesia, and the specimen (Figure 2) was sent for histological examination.
Diagnosis
USG-guided fine-needle aspiration (FNA) smears revealed moderate cellularity (Figure 3), showing a cluster and dissociated singly scattered cells with ovoid nuclei and ill-defined cytoplasmic borders (Figure 4). A few plump and slender spindle cells were observed (Figure 5). An impression of cytological features in favor of a spindle cell tumor was made.
The excised tumor was subjected to a histological examination. It was a single globular specimen with attached fibroadipose tissues and skin (Figures 6, 7). The total dimensions of the specimen were 8 cm x 3.5 cm x 2.5 cm. The tumor was globular and white in color. The cut surface was homogenous white, soft to firm, and measured 3.5 cm x 3.5 cm x 3.5 cm in size.
On microscopy, sections from different areas revealed a nodular mass composed of a proliferation of mostly uniform, medium-sized spindle cells with a storiform or cartwheel pattern of growth (Figures 8, 9) placed in the dermis and extending into the subcutaneous adipose tissue (Figure 10). It was separated from the epidermis by a grenz zone. Adnexal structures were also embedded in the tumor. The overlying epidermis appeared normal (Figure 11). The tumor infiltrated the subcutaneous adipose tissue in a honeycomb pattern. Histological features suggestive of dermatofibrosarcoma protuberans were observed.
Follow-up and outcomes
Post-operation, the patient was relieved of acute symptoms of pain and swelling over the right side of her back. Her discomfort had subsided. Overall, the patient was doing quite well after the surgical intervention. | case report, dermatofibrosarcoma protuberans, histopathology, lumbar region, spindle cells | Not supported with pagination yet | null |
PMC6104584_01 | Male | 6 | Culture studies from the biopsy were performed and grew Mycobacterium tuberculosis. Sequencing identification of the pathogen by the CDC matched that of patient zero, a transient adult male that lived in the same city and was the source of multiple exposures. In the case of our patient, epidemiological studies showed that he was likely exposed to TB on an ED visit when he was 6 years old and was being seen for chronic lung disease exacerbation.
The patient was started on isoniazid, rifampin, pyrazinamide, and ethambutol. However, during the first two weeks of treatment, he began to have feeding difficulties and developed jaundice. Alanine transaminase (ALT) and aspartate aminotransferase (AST) were five times the normal range. All TB medications were stopped until ALT and AST returned to normal. Rifampin was restarted, but the patient again developed jaundice and elevated liver enzymes. We determined that he could not tolerate rifampin and placed him on double therapy of isoniazid and ethambutol for 24 months. The patient performed well with therapy whereby there were resolution of granulation tissue and no AFB found on post-treatment biopsy.
Three months after the completion of treatment, the patient underwent a VPS revision without complications during the procedure. However, six months later, he developed a new erythematous, non-pruritic rash with oozing at the site of incision of the shunt revision on the scalp. A new biopsy was obtained which showed multiple AFB, thereby resulting in his diagnosis of recurrent cutaneous TB. Due to the hepatotoxicity of the first treatment plan, the patient was placed on intravenous amikacin, oral cycloserine, and oral ethionamide for three months and subsequently, amikacin was replaced with levaquin. The triple therapy was maintained for 18 months with resolution of the lesion. Given the recurrent nature of the patient's TB, he was placed on prophylaxis isoniazid and ethambutol with no documented recurrence TB throughout the remainder of his life. He succumbed from unrelated complications of his chronic disease. | null | Not supported with pagination yet | null |
PMC9805620_01 | Male | 24 | A 24-year-old male patient presented to us with global aphasia and right-sided hemiplegia. Medical history was significant for intermittent headaches for 4 months. One month after the onset of symptoms, the patient developed an evening rise in temperatures and abdominal pain. He sought treatment at another institution where he was evaluated with ultrasound abdomen that showed splenomegaly with multiple granulomas and the findings were later confirmed with computerized tomography (CT) abdomen which also revealed periportal, para-aortic, and aortic caval lymphadenitis-like features, for which he was treated presumptively as a mycobacterial tuberculosis infection. Ten days later, the symptoms worsened and the patient developed new-onset speech difficulty along with right-sided weakness. Consequently, the patient was evaluated with a magnetic resonance imaging (MRI) brain which was suggestive of left frontal thin subdural (measuring around 2*3*2 mm, volume 6 cubic mm) and a rim of thin epidural collection, and the patient was continued on anti-tubercular treatment (ATT) presuming CNS tuberculosis.
A month later, he presented to us when complaints progressed to aphasia and hemiplegia. Physical examination was significant for altered sensorium with a Glasgow Coma Scale of E3VAM5 and right-sided hemiplegia. The patient was reevaluated with a plain and contrast MRI of the brain. On T1, isointense rim with the hypointense collection was noted in the lesion [Figures 1a and 1b], findings confirmed in T2 sequence with fluid-fluid level, also T2 and MR flair sequence shows hyperintense extra-axial/subdural collection [Figures 1c and 1d]. MRI contrast scan featured conglomerate peripheral ring-enhancing lesions [Figures 1e and 1f] in the left frontal lobe (intraparenchymal) with moderate to significant perilesional edema causing mass effect over the frontal horn and body of the ipsilateral ventricle. Diffuse weighted imaging was suggestive of diffusion restriction within the wall of the lesion and in the dependent content and debris [Figure 1g]. Magnetic resonance (MR) spectroscopy showed significantly large lipid lactate peaks in the lesion [Figure 2a]. Findings favored infective etiology with cerebral abscess, subdural empyema, and dural thickening with an intradural abscess in the left frontal region with frontal cortical vein thrombosis. Radiological findings were confirmed intra-op, subsequently was compared with post op scan which showed complete abscess evacuation [Figure 2b].
The patient underwent left fronto-temporo-parietal decompressive craniectomy and abscess evacuation. After craniectomy, adherent purulent collection was noted on the inner table of the bone flap and dura, suggestive of osteomyelitis and epidural abscess [Figure 3a]. Durotomy was performed and thick pus was noted in the subdural plane [Figure 3b] which was evacuated. Subsequently, the abscess was approached through a pial incision over the superior frontal gyrus at the point of tense thickened pia; clear differentiation was seen between the capsule and surrounding glial tissue. The capsule was incised with a stab, purulent contents were evacuated, the leftover capsular wall was excised, and hemostasis was achieved. The osteomyelitic bone and raised intracranial pressure features were indications for not replacing the bone flap. The histopathology and culture evaluation grew B. pseudomallei, subsequently, he was started on intravenous antibiotics and the postoperative contrast-enhanced CT showed complete abscess evacuation with a significant reduction of perilesional edema [Figure 2b]. Recovery was uneventful with aphasia resolution and right-sided motor power improvement. At 1-month follow-up, the patient had significant neurological improvement with no new deficits. | abscess, burkholderia, epidural, intraparenchymal, melioidosis, subdural | Not supported with pagination yet | null |
PMC4748778_01 | Male | 41 | A healthy 41-year-old male presented with a 2-year history of increasingly blurry vision in the right eye. His review of systems was otherwise negative. He had a family history of skin cancer in his father and leukemia in his cousin. Visual acuity was hand motions in the right eye and 20/20 in the left eye. Pressure was 16 OU. Slit-lamp biomicroscopy showed trace nuclear sclerotic cataracts in both eyes with no other abnormalities. Dilated examination of the right eye revealed a retinal detachment and an amelanotic subretinal mass extending from the posterior pole and tapering into the periphery (fig. 1).
Color fundus photography revealed an exudative retinal detachment and an elevated whitish subretinal/choroidal mass lesion in the posterior pole. Fluorescein angiography revealed early hypofluorescence with minimal late hyperfluorescence. An MRI of the brain and orbit showed a 5-mm right choroidal mass in the posterior globe with no other intracranial findings, and OCT also revealed choroidal thickening. All of these findings were highly suggestive of uveal lymphoma and help to differentiate this lesion from primary vitreoretinal lymphoma, which typically shows hyperreflective nodules at the RPE level and sub-RPE space on OCT, and clusters of round, hyper- or hypofluorescent lesions on fluorescein angiography. The remainder of the workup was negative, including CT of the chest/abdomen/pelvis, CMP, LDH, CBC with differential, ACE, RPR, and quantiferon TB-gold.
Transcleral fine needle aspiration biopsy of the choroidal lesion was performed. Immunohistochemical staining of the cell block revealed a population of predominantly CD20-positive B lymphocytes with comparatively fewer CD3- and CD5-positive T cells. No co-expression of CD5 and BCL-1 was appreciated. IgH gene rearrangement for IgH V-D-J revealed a monoclonal population of B lymphocytes, consistent with lymphoma (fig. 2).
The patient was treated with external beam radiation therapy (EBRT). Imaging obtained 4.5 months after ERBT showed excellent regression of the uveal mass, significantly reduced thickness of the choroidal lesion, resolution of the retinal detachment, and no signs of subretinal fluid. OCT demonstrated residual subretinal scarring (fig. 1). The patient's visual acuity remained hand motions. | fluorescein angiography, histopathology, optical coherence tomography, primary uveal lymphoma | Not supported with pagination yet | null |
PMC9397973_01 | Male | 62 | The participant is a 62-year-old male suffering from NP due to a complete spinal cord injury at T8 that occurred in year 2010. The patient had noted that no medication or other therapy had improved pain symptoms in the past. He had an intrathecal baclofen (ITB) pump therapy introduced in 2017. Subsequently, patient has been tried with several other options including, acupuncture, IV lidocaine therapy, opioids (both oral and intrathecal), gabapentin, and others. During the time of this study, his medications included gabapentin, cymbalta, zopiclone, and oxybutynin. Due to the refractoriness and severity of pain, the patient was referred by the neuromodulation team at Hamilton Health Sciences to take part in this study. The patient suffered from daily prolonged pain in the lower limbs, buttocks, and trunk including burning and electrical shock-like sensations. Four pain phenotypes were identified by the patient and tracked throughout this study. These pain phenotypes began within the first month following the injury and have been consistent for the 11 years prior to beginning the study. These pain phenotypes included:
Left foot: Described as a continuous intense pressure that feels like the skin on the foot is going to burst. Rated at baseline as a 7/10 on the numeric rating scale.
Sternum: When sternum is touched it causes burning pain in sternum area. Only occurs if sternum is touched. Rated at baseline as a 10/10 on the numeric rating scale.
Buttocks: Described as a continuous sharp electrical type of pain/ burning in the lower pelvic tailbone area. Rated at baseline as an 8/10 on the numeric rating scale.
Electrical attacks: Described as attacks of sharp circulating electrical pain that would begin in the left flank and radiate throughout the torso (back and core). Would occur 2-3 times per day and would last up to a minute. Rated at baseline as a 10/10 on the numeric rating scale. | baclofen pump, intrathecal pump, neuropathic pain, rtms, repetitive transcranial magnetic simulation, spinal cord injury | Not supported with pagination yet | null |
PMC6354650_01 | Female | 11 | An otherwise well 11-year old girl presented with a 3-day history of chest pain and cough. The girl had been given clarithromycin 2 months earlier for cough and fever under the presumptive diagnosis of lower respiratory system infection. Chest X-ray revealed a cavitary lesion at the left lower lobe, and smaller lesions at the middle and upper lobes bilaterally (Fig. 1a). High resolution computed tomography (HRCT) confirmed the presence of multiple cavities which were located at the left upper lobe and at the superior segment of the collapsed left lower lobe, calcified subcarinal and hilar lymphnodes, and bilateral nodular non-cavitary parenchymal disease at the upper lobes (Fig. 1b and c). Mantoux tuberculin skin test showed an induration of 30 x 30 mm and interferon gamma release assay (IGRA, Quantiferon-TB, Cellestis) test was positive. No BCG vaccination was recorded and no BCG scar was evident. Sputum smear for acid fast bacilli stained positive, and PCR, culture of sputum and gastric aspirate all grew M. tuberculosis. Sensitivity to isoniazid, rifampin, streptomycin and ethambutol was shown by the BACTEC MGIT 960 SIRE test (Becton, Dickinson and Company, USA) and no mutation indicating resistance to antituberculous drugs was detected by Genotype MTBDR plus and MTBDRsl test (Hain, Germany) based on DNA-STRIP technology. Serology for HIV was negative and immunology work-up was normal. Isoniazid, rifampin, pyrazinamide and ethambutol were given for 2 months, followed by isoniazid and rifampin for 4 more months. Methylprednisolone was given for the first 3 weeks. Sputum staining was negative after 3 weeks of treatment. The girl had not attended school for the past 6 months for social reasons and was the second of three children of a family of Bulgarian origin. Positive family history or recent contact with tuberculosis was not reported. Following contact investigation, all family members were given chemoprophylaxis for positive tuberculin skin test and IGRA assay, but normal chest X-ray.
An 8-year old boy with B-cell acute lymphoblastic leukaemia, presented with fever, cough and respiratory distress while on maintenance chemotherapy. Chest radiographs suggested prominent hilums and a cavitary lesion at the left lower lung field (Fig. 2), while HRCT showed enlargement of paratracheal, hilar and mediastinal lymphnodes, consolidation at the lingula containing a small cavity and multiple pulmonary nodular lesions at the superior segment of the left lower lobe, the lateral segment of the right middle lobe and the posterior segment of the right lower lobe. There was no evidence of significant tracheal compression. Mantoux tuberculin skin test was negative, whereas IGRA test was positive. Gastric lavage grew M. tuberculosis which was susceptible to all drugs. The boy was successfully treated with isoniazid, rifampin, pyrazinamide and ethambutol for a total of 18 months (for isoniazid and rifampin) and methylprednisolone for 8 weeks. Outcome was uneventful over a 4-year follow-up period. CD4:CD8 ratio was 0.3 and remained low for a long period. The child originated from Albania and occasionally made visits to relatives there. He was not vaccinated with BCG. The source of infection was not identified, despite an investigation which included family and contacts as well as school mates and staff (34 individuals). A school teacher had recently received chemoprophylaxis, but did not have cavitary lesions. All children at school had already received BCG according to the Greek national immunisation programme. Chemoprophylaxis was given to three of them who presented with positive Mantoux test and positive IGRA assay, normal chest x-ray and normal first-line investigation results. | cavitary tuberculosis, children, immigrants, immunocompetent, immunocompromised | Not supported with pagination yet | null |
PMC6744813_01 | Female | 66 | A 66-year-old right-handed lady was diagnosed with Huntington's disease (HD)-like 4 disorder due to SCA17 mutation (43 CAG/CAA-repeats in TBP gene) at the age of 54. Disease onset was characterised by gait imbalance, falls and fidgetiness. Over the years, a progressive mood decline and cognitive deterioration accompanied the motor symptomatology. Concerning her family history, three of her siblings were similarly affected by generalised involuntary movements.
On examination, she presented with motor impersistence on eye-movement assessment and tongue protrusion. Involuntary choreic movements affected the face and limbs. The gait was broad-based. Severity of ataxia was rated with the SARA scale (25/40). Gait (4/8), stance (4/6) and speech (4/6) were significantly impaired; finger-chase test, nose-finger test, fast alternating movements and heel-shin test were as well severely affected (3/4); on sitting, there were slight difficulties with intermittent sway (1/4).
Brain MRI disclosed a severe cerebellar volume loss. On the neuropsychological assessment, the most notable finding was a significant executive dysfunction. All the other domains assessed, including memory (MMSE 21/30), visual perceptual skills, reading, naming, praxis and speed of information processing, were equally impaired.
In the last 2 years, her husband reported the development of self-injurious behaviour, namely scratching of the skin resulting in severe excoriations of the chest, arms and lower limbs. She denied itchiness. According to the partner, the skin scratching seemed to be preceded by an urge of action followed by a subsequent relaxation.
This lady noticed for the first time a turning of the legs and curling of the hands at the age of 48. She had a family history of depression, anxiety and dementia, and reported to suffer from low mood too. On examination, she presented with generalised chorea and some difficulty with tandem gait. There were skin wounds in the upper limbs caused by repetitive self-injuring acts. Nevertheless, she was not able to report whether inner pressure or relief related to the skin scratching was experienced. Attention, concentration and memory were mildly impaired. She was admitted to hospital for further investigation. Brain MRI was normal, while the genetic screening revealed an abnormally expanded 50 CAG/CAA-repeats in TBP gene and a diagnosis of SCA17 was then confirmed. | sca17, dopamine, neurotransmitters, self-injury, serotonin | Not supported with pagination yet | null |
PMC8749145_01 | Female | 85 | A total of nine cases were included over a period of 8 months. Their demographic and clinical details are described in Table 1. Eight patients were adults with an age range from 25 to 85 years and one patient was a 6-year-old child. Seven patients were male and two were female. Two patients had co-morbid conditions; one was on anti-retroviral treatment and the other had diabetes mellitus with hypertension. Patients presented with atypical symptoms such as discharging sinus, ear lobule swelling, otitis media, vision loss and facial weakness, long refractory otorrhoea and granulation tissue in the ear canal. One patient had complained of right vision loss, proptosis and headache for 6 months. One of these nine patients had coexistent pulmonary tuberculosis. None of the patients had a significant past or family history. All patients were suffering for a long span of time and were non-responsive to broad-spectrum antibiotics. External auditory canal, laryngoscopy and audiometry examination showed atypical features that were consistent with tuberculosis or neoplasms. Radiological investigations showed typical features of osteomyelitis of the temporal bone and skull base, and others, such as destruction of bone, increased bone uptake and densities, which needed further evaluation (Table 2, Fig. 1). Histopathological evaluation revealed granuloma in few cases and atypical features in some, suggesting neoplasm. We were able to diagnose involvement of the temporal bone (two cases), tubercular skull base osteomyelitis (one case), mastoid bone (one cases), larynx (two case), sino-nasal (one case), maxillary sinus (1one cases) and ear lobule (one case). Microbiological examination of samples confirmed the cases (Table 2). All samples were acid-fast bacilli-positive (ZN staining), while GeneXpert was positive in four cases for MTB and TrueNat was positive in all nine cases and detected MTB (four cases) and NTM) (five cases (Table 2). All patients were managed successfully with a combination of surgical and combination regimens including antibiotics (NTM cases) and anti-tubercular drugs, except one tubercular skull base osteomyelitis patient, who expired before the initiation of anti-tubercular therapy (ATT) (Table 3). | mycobacterium tuberculosis, laryngeal tuberculosis, maxillary tuberculosis, non-tuberculous mycobacteria, skull base osteomyelitis | Not supported with pagination yet | null |
PMC5457922_01 | Male | 73 | A 73-year-old man with delirium was admitted to our hospital complaining of left sternoclavicular joint pain. He had a history of diabetes mellitus, dyslipidemia, and stent placement for right renal arterial stenosis in 2011. In early August 2013, he experienced pain around the left sternoclavicular joint, and approximately the same time, he was unable to use either the television remote control or his car seatbelt. Although he visited his local physician several times, his symptoms did not improve and blood tests revealed no significant abnormalities except for an elevated CRP level. In mid-August, he developed delirium, and came to our hospital for detailed examination.
Physical examination findings on admission included: height, 160 cm; weight, 63 kg; body temperature, 36.8 C; blood pressure, 150/89 mmHg; and heart rate, 100 beats/min. Pressure pain was observed in his chest at the left and right sternoclavicular joints, sternum, and near the right fourth and fifth ribs. Examination of the head, abdomen, back, and limbs revealed no abnormalities, and no lymph node swelling was noted. Neurologically, the patient presented with slightly reduced consciousness; his Glasgow Coma Scale score was 14 (E4V4M6); however he scored 9 of a possible 30 on Hasegawa's Revised Dementia Scale. No neck stiffness was seen, and no cranial nerve, motor system, or sensory system abnormalities were observed. No symptoms of Parkinsonism, such as muscle rigidity and tremors, were noted.
Laboratory testing performed on admission revealed the following: white blood cell count, 7.4x103/muL (reference range: 4.5-7.7x103/muL); CRP, 20.04 mg/dL (reference range: 0.0-0.3 mg/dL); red blood cell count, 3.13x106/muL (reference range: 4.32-5.07x106/muL); hemoglobin, 8.3 g/dL (reference range: 13.5-15.7 g/dL); serum iron, 33 mug/dL (reference range: 100-150 mug/dL); ferritin, 1,276.6 ng/mL (reference range: 18.6-261 ng/mL); blood glucose, 254 mg/dL (reference range: 70-109 mg/dL); and hemoglobin A1c, 8.6% (reference range: 4.6-6.2%). Electrolytes, vitamins, renal function, and hepatic function were normal. Blood coagulation testing revealed fibrin degradation products, 5.5 mug/mL (reference range: 0-10 mug/mL), and D-dimer, 1.2 mug/mL (reference range: 0.0-1.0 mug/mL). Serum immunological testing revealed no specific abnormalities. Levels of tumor markers revealed that soluble interleukin-2 receptor (sIL-2R) level was 1,350 IU/mL (reference range: 124-466 IU/mL), and no other abnormalities. As indicated, blood test results showed elevated levels of CRP, ferritin, sIL-2R, fibrin degradation products, and D-dimer. Examination of cerebrospinal fluid revealed a nucleated cell count of 0/muL (reference range: 0-5/muL); protein, 83 mg/dL (reference range: 10-40 mg/dL); glucose, 102 mg/dL (reference range: >one half of blood sugar); anti-N-methyl-D-aspartate antibody was negative. Results of polymerase chain reaction testing for herpes simplex virus deoxyribonucleic acid (DNA) and cytodiagnosis were negative. Magnetic resonance imaging (MRI) of the head revealed no particular abnormalities.
Following admission, the patient often developed severe delirium at night and complained of pain in the left and right sternoclavicular joints, sternum, and right fourth and fifth ribs. MRI of the mediastinum revealed a low-intensity signal in the sternum on T1-weighted imaging (T1WI) and a high-intensity signal on T2-weighted imaging (T2WI) and fat-suppressed T2WI (Fig. 1). A low-intensity signal was observed in the right pedicle of the upper thoracic spine on T1WI, and a tumor shadow with a high-intensity signal was seen on T2WI. Gallium scintigraphy revealed abnormal uptake in the sternum (Fig. 2). Further blood test results showed an elevated CRP level; however, there were no signs of infection, such as fever. Results of blood, urine, and cerebrospinal fluid cultures were also negative. The primary tumor could not be identified by MRI or scintigraphy findings. However, a metastatic or multifocal bone tumor was suspected. After two weeks of testing to identify a primary tumor lesion, the patient developed vomiting and abdominal pain and subsequently died.
An autopsy was performed approximately 2 hours after the patient's death. Macroscopic pathological findings revealed necrosis extending from the duodenum to the ileum. No macroscopic lesions were observed in the ribs or vertebrae, and no macroscopic masses were observed in the lungs, esophagus, stomach, intestinal tract, liver, spleen, pancreas, bladder, prostate, testicles, or kidneys. Calcification was seen in the coronary arteries, but no valve vegetation was observed. No macroscopic masses were observed in the aorta from the chest to the abdomen. Spindle tumor cells were observed microscopically in the abdominal aortic intima. We could not find tumor cells in lymphatic vessels. Immunohistochemical staining of tumor cells were positive for vimentin (Fig. 3), which suggests that the tumor cells were derived from mesenchymal cells. Among other tested markers, AE1/AE3, S-100 protein, CD56, and desmin were negative; alphaSMA (smooth muscle actin) and HHF-35 (muscle-specific actin) were almost negative; and Ki-67 was positive for 16% cells. Spindle tumor cells were observed in the superior mesenteric artery (Fig. 4). Proliferation of spindle tumor cells was observed in the ribs, thoracic vertebrae, sternal medullary cavity near the sternoclavicular joint, and peritracheal lymph nodes (Fig. 5). No tumor cells were seen from the ascending aorta to the thoracic aorta, pulmonary artery, or renal artery stent. In the neuropathological examination, no tumor cells were seen in the brain. Several Lewy bodies were observed throughout the entire cerebral cortex and brain stem. However, there was not severe neuronal loss in the cerebral cortex and was not apparent gliosis. No perivascular lymphocytic infiltration and no cerebellar degeneration were seen. Based on these findings, we diagnosed abdominal aortic intimal sarcoma with multifocal bone metastasis and peritracheal lymph node metastasis. | null | Not supported with pagination yet | null |
PMC9549081_01 | Female | 46 | A 46-year-old female refugee from the Dominican Republic with a history of hypertension presented at our outpatient clinic for management of left axillary HS, previously diagnosed 4 years ago in her country. Her HS nodules were confined to her left axilla and first presented four years prior. She denied ever having lesions in other folds. She had previously received courses of antibiotics in her country with limited improvement.
She was initially treated with intralesional triamcinolone, topical clindamycine, and oral doxycycline. At her 2-month follow-up, the nodules had progressed, and she now presented two subcutaneous fluctuant masses underlying the HS nodules.
On examination, three tender erythematous nodules with friable granulation tissue and sinus tracts were visible in the left axilla. On both the superior-lateral quadrant of the left breast and pectoral region, two large subcutaneous fluctuant masses were palpated. A solitary left cervical adenopathy was also palpated. No double comedones or HS nodules were visible in her axilla or other folds.
Basic laboratory workup was unremarkable. The patient was referred to radiology for a surface ultrasound of the axilla, which demonstrated three heterogenous fluid collections in the left deltopectoral groove (5 x 2 x 3 cm), left subclavian space (1.8 x 1.6 cm and 2.8 x 2.4 cm), and supero-lateral quadrant of left breast (4.5 x 3.4 x 3.7 cm), all suggestive of suppurative adenitis. At this time, an ultrasound-guided aspiration of the fluid was conducted, which was positive for M. tuberculosis by polymerase chain reaction (PCR). Additional mycobacterial, bacterial, and fungal cultures of the fluid were negative. Chest X-ray and cervicothoracic computed tomography (CT)-scan showed normal pulmonary parenchyma and were negative for extra-axillary abnormalities. Cultures of sputum for M. tuberculosis were negative. She was not tested for HIV antibodies.
A diagnosis of scrofuloderma of the left axilla without pulmonary involvement was made. Infectious diseases were consulted, and the patient was treated with a combination of isoniazid, rifampicin, pyrazinamide, ethambutol, and vitamin B6. She was asked to self-isolate until the results of her sputum cultures were confirmed negative.
After 6 months of treatment, the patient demonstrated a near-complete resolution of the adenitis on follow-up CT-scan. | dermatology, infectious disease | Not supported with pagination yet | null |
PMC395840_01 | Female | 25 | We herein describe a case of allergy to lingonberry in a 25-year-old woman with a history of mite allergic rhinitis, but no food allergies. She entered a restaurant and then ate meatballs, baked potatoes and lingonberry jam. During the meal, itching wheals developed around her mouth. Symptoms were solved without treatment. The patient was not under any treatment on that time. Skin prick testing by prick-prick method with fresh lingonberry revealed mean wheal diameter of 5 mm and mean flare diameter of 20 mm (Figure 1a). Skin tests either with the foodstuffs involved in the episode or other berries showed no reaction. On her responsibility and against medical advice, she subsequently took a very little amount of lingonberry jam several days later. She immediately noticed more intense symptoms with intense itching on mouth, tongue and throat and wheals over her mouth. Symptoms were solved in an hour without treatment. | null | Not supported with pagination yet | null |
PMC5509186_01 | Male | 40 | A 40-year-old man who had been generally healthy came to our hospital in June 1996, with chief complaints of fever with chills and malaise for 2 months. He also had a weight loss of 8 kg within 1 month. Physical examination showed right cervical lymphadenopathy and a posterior pharyngeal tumor. The cervical lymph node proved to be tuberculosis on biopsy and acid-fast stain and the posterior pharyngeal tumor showed KS on histology. An abdomen to pelvic computed tomography (CT) scan did not show any abnormal lesion in the liver, spleen, and bilateral kidneys. Both HIV enzyme-linked immunosorbent assay and western blot were positive for HIV-1. The serologic test for syphilis was positive. He was treated with a combination of three antituberculosis drugs (ethanbuthol, pyrazinamide, isoniazid), acyclovir for herpes simplex virus infection, ceftriaxone, amikacin, and trimethoprim-sulfamethoxazole. He began receiving zidovudine in October in 1996. This was replaced by didanosine (ddI) 1 month later because of refractory bone marrow suppression.
At his second admission to our hospital in December 1996, multiple skin lesions were found over his chin and anterior neck. Excisional biopsies of those lesions revealed cutaneous KS. The CD4+ T-cell absolute count was only 18 cells/muL. Tuberculosis, syphilis, candidiasis, and cytomegalovirus retinitis were diagnosed and treated. The antiretroviral drug ddI was discontinued in January 1997. Bilateral pulmonary infiltrations were observed in chest radiographs. Pneumocystic pneumonia was impressed and treated with trimethoprim-sulfamethoxazole. The symptoms had improved at the time of hospital discharge.
The patient was admitted again 1 month later for dyspnea and cough with sputum production for 2 weeks. More immunosuppression was noted with a CD4+ T-cell absolute count of 10 cells/muL. HAART was initiated in April 1997 with zalcitabine, lamivudine, and saquinavir. The pre-HAART serum HIV RNA level was 313.1 x 103 copies/mL.
The HIV viral load decreased to 20.93 copies/mL (4 log10 drop) at 32 days after initiation of HAART. Meanwhile, the CD4+ T-cell count increased to 41 cells/muL (4-fold rise). However, the patient's skin lesions progressed to involve the trunk, all extremities, the perianal region, and foreskin of the penis. He received amputation of the right big toe because of KS following a biopsy.
After 5 months, the patient developed fever with dyspnea. Bilateral diffuse pulmonary infiltrations were observed again in plain chest radiographs. Despite treatment with antituberculosis drugs, HAART, trimethoprim-sulfamethoxazole, cephapirin, and gentamycin, he died approximately 6 months after starting HAART.
At autopsy, multiple KS lesions were seen over the chin, neck, left flank, four extremities, perianal area, and prepuce of the penis, mostly presenting as nodular or ulcerative lesions. Two tumor masses were seen between the tonsils and between the tongue base and oropharynx. No pleural effusion was seen in the thoracic cavity. The right and left lungs weighed 750 and 780 g, respectively, and had thickened pleurae and foci of adhesions. Some hemorrhagic nodules were seen on the pleural surfaces. On cutting, hemorrhagic, yellowish nodules involving all segments of all lobes were found [Figure 1a]. The hilar nodes and paratracheal nodes were also involved by tumors. Serous ascitic fluid 300 mL was obtained from the abdominal cavity. Some foci of KS lesions were observed in the liver appearing as small nodules [Figure 1b]. The kidneys weighed 120 g each and were also involved by KS, especially in the cortical areas [Figure 1c]. In the gastrointestinal (GI) tract, many KS nodules were observed in the mucosa of the stomach (especially at the lesser curvature), duodenum, jejunum, ileum, colon, and anal canal. Those tumors presented with polypoid, nodular, and/or ulcerative patterns [Figure 1d-g].
Microscopically, all representative tumor nodules were composed of spindle cells in fascicles or bundles or storiform, vascular channels filled with erythrocytes lined by flat endothelial cells and extravasated erythrocytes [Figure 2a], with HHV-8 antigen positivity [Figure 2b], diagnostic of KS. Multiple disseminated KS nodules involving the lungs surrounded the bronchioles and vessels (bronchocentric and angiocentric patterns), which were the cause of death in this patient [Figure 2c].
The patient had no lesions in the liver, kidneys, or GI tract in the abdomen to pelvic CT scans taken in June 1996. Multiple disseminated KS was observed in several visceral organs at autopsy. Skin KS progression was noted 1 month after HAART in spite of a rise in the CD4+ T-cell count and a significant reduction in the viral load. Thus, his rapid progression before death could be explained as a consequence of IRIS. | acquired immune deficiency syndrome, human immunodeficiency virus, immune reconstitution inflammatory syndrome, kaposi's sarcoma | Not supported with pagination yet | null |
PMC9932891_01 | Male | 36 | A 36-year-old man with a 20-year history of nephrotic syndrome with normal renal function and fluctuating urine protein levels had been treated with glucocorticoids and traditional Chinese medicine for more than 10 years. He was first hospitalized due to abnormal liver function. Routine laboratory tests revealed mild abnormal liver function [total bilirubin (TBIL) 41.9 micromol/L, direct bilirubin (DBIL) 22.7 micromol/L, alanine aminotransferase (ALT) 21.6 U/L, aspartate aminotransferase (AST) 81.1 U/L, gamma-glutamyl transferase (GGT) 517.5 U/L, alkaline phosphatase (ALP) 323 U/L]. Doppler ultrasound, CT scan, and contrast-enhanced MRI scan of the upper abdomen demonstrated multiple small masses in the liver, so hemangioma was considered. Also, the enlarged spleen and collateral vessels indicated the presence of portal hypertension. The patient underwent a percutaneous liver biopsy and soon after felt pain and discomfort in the right upper abdomen with transient blood pressure decline. The ultrasound confirmed bleeding and hemorrhagic shock due to the liver biopsy. The patient recovered after fluid rehydration, blood transfusion, and other supportive treatments. Pathological examination of the liver biopsy ( Figure 1A ) revealed congested hepatic sinusoids and peri-sinusoid fibrosis, as well as dilation of the interlobular veins and some extended into the surrounding hepatic sinus. These changes in liver histology were consistent with NCPH features that represent venous outflow stenosis with portal hypertension. There was no evidence of extra-hepatic portal vein obstruction, and the patient was diagnosed with a drug-induced liver injury [the Roussel Uclaf Causality Assessment Method (RUCAM) score 5] and secondary NCPH. Ursodeoxycholic acid was given, and regular outpatient follow-up was performed.
Three months after discharge, an outpatient contrast-enhanced MRI scan of the upper abdomen depicted enlarged hepatic masses. Considering the possibility of malignancy ( Figure 1D ), the patient was readmitted to the hospital. Routine laboratory tests revealed abnormal liver function [albumin (ALB) 21 g/L, TBIL 35.7 micromol/L, DBIL 14.0 micromol/L, ALT 67 U/L, AST 70 U/L, GGT 147 U/L, ALP 240 U/L]. Liver contrast-enhanced ultrasound and positron emission tomography-computed tomography (PET-CT) indicated the possibility of primary liver malignancy with intratumoral hemorrhage. Whole abdominal CTV demonstrated multiple masses in the liver and an enlarged spleen with a spleen-renal venous shunt ( Figure 1E ). The patient was transferred to the hepatobiliary surgery department and underwent laparoscopic resection of the liver lesions. Liver lesion biopsy pathology ( Figures 1B, C ) demonstrated that the tumor cells were slit and cable-like with a vascular network and growth along the liver sinusoids. Immunohistochemistry revealed high expression of CD34, CD31, and ERG (ETS transcription factor).
The patient was diagnosed with primary hepatic angiosarcoma and was treated with lenvatinib. In May 2020, he stopped taking lenvatinib due to progressively exacerbating liver function and died of severe intra-abdominal infection and acute kidney failure. | diagnosis, noncirrhotic portal hypertension, pathology, primary hepatic angiosarcoma, treatment | Not supported with pagination yet | null |
PMC4395955_02 | Female | 0 | The pus stained positive for acid-fast bacilli (Ziehl Neelsen stain) while the Gram stain was negative [Figure 2]. On histopathology, the wall of the abscess composed of necrotizing granulomatous inflammation, suggestive of tuberculous infection; while the dermal sinus examination revealed chronic inflammation and fibrosis. The pus culture was negative. Mycobacterium tuberculosis (MTB) was detected on MTB DNA polymerase chain reaction. The baby responded well to anti-tubercular treatment. A retrospective search for finding out the source of infection proved unsuccessful. The patient was a 4-month-old baby having received Bacillus Calmette-Guerin (BCG) vaccination at birth, with no other focus of tubercular infection elsewhere in the body. The mother with all family members, including the servants were screened for tuberculosis with chest X-ray and three serial early morning sputum examinations, but none tested positive. She was discharged on anti-tubercular treatment and physiotherapy. Follow-up MR scan showed good resolution of the intramedullary abscess. | intramedullary, spinal cord abscess, tubercular abscess | Not supported with pagination yet | null |
PMC4405938_01 | Male | 22 | The study was conducted between January 2006 and June 2010 at the TB Laboratory, Division of Clinical Microbiology and Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India. This study was approved by the Institutional Ethics Committee of AIIMS and written informed consent was obtained from the patient. The patient was being treated at the designated microscopy and DOTS (directly observed treatment-short course) centres of Shahpurjat, New Delhi. This patient (22 yr old male) was diagnosed as having pulmonary TB on the basis of clinical and radiological findings and sputum smear microscopy. He was prescribed with anti-TB treatment (ATT) under the DOTS programme. The thrice a week treatment regimen comprised isoniazid, rifampicin, pyrazinamide (PZA) and ethambutol (EMB) (category I treatment) in intensive phase for two months followed by four month treatment with two (isoniazid and rifampicin) drugs regimen. Pre-treatment sputum specimen was used for isolation of Mycobacterium sp. by BACTEC MGIT-960 (Becton Dickinson, Sparks, MD, USA), which was positive. The isolate was identified as Mtb by conventional phenotypic and in-house PCR method. This culture was labelled as isolate A, and was subjected to 16sRNA gene sequencing. The patient though took full six months course of treatment but became irregular in taking drugs after initial improvement in his clinical symptoms. After three months of cessation of treatment (6+3= 9 month, his condition again deteriorated and his sputum culture was again positive for Mtb. We labelled this second culture as isolate B. He was re-treated with isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin (SM) (category II regimen). Within two months his clinical condition improved but he again defaulted. After an asymptomatic period of about four months his symptoms reappeared. His sputum was again culture positive and this culture was labelled as isolate C. The patient was again prescribed with the same treatment for 12 months after counselling but he stopped treatment after six months. His condition further deteriorated and he died of multisystem failure. The fourth sample was received just before his death and the isolate from this sputum sample was labelled as isolate D.
All the four clinical isolates (A, B, C & D) were identified as Mtb using standard protocols. The anti-mycobacterial drug susceptibility testing was performed on all the isolates by both BACTEC MGIT-960 (Becton Dickinson, Sparks, MD, USA) and proportional method using Middlebrook 7H10 (Difco, USA) agar plates containing first-line anti-TB drugs (SM 2.0 microg/ml, INH 0.2 microg/ml, RIF 1.0 microg/ml, EMB 6.0 microg/ml). All four isolates were also genotyped by spoligotyping and identified using SITVIT-WEB database. The rpoB, inhA and katG gene targets were sequenced using the primers as described elsewhere.
Preparation of mycobacterial whole cell lysate: All Mtb isolates were grown without shaking in Middlebrook 7H9 medium supplemented with 0.2 per cent (v/v) glycerol, 10 per cent oleic acid, albumin-dextrose and catalase (OADC, Difco, USA) at 37 C for two weeks. Whole cell lysate was prepared according to protocol of Sharma et al. Cells were washed three times with normal saline and then suspended in sonication buffer [50 mM tris-HCl containing 10 mM MgCl2, 0.1% sodium azide, 1 mM phenylmethylsulfonyl fluoride (PMSF) and 1mM ethylene glycol tetra acetic acid (EGTA); PH 7.4] at a concentration of 1g wet cell mass per 5ml, and then broken by intermittent sonication for 15 min at 4 C using sonicator (Sonics & Materials Inc, USA). The homogenate was centrifuged at 12,000xg for 20 min at 4 C. The pellets were discarded and supernatant was stored at -70 C until further use.
Protein precipitation with sodium dodecyl sulphate (SDS)-trichloroacetic acid (TCA)-acetone: The cell lysates were treated with 1 per cent SDS and then subjected to TCA-acetone precipitation procedure. The protein pellet was suspended in appropriate volume of two-dimensional rehydration buffer (Bio-Rad, USA), and the protein concentration was estimated using the Bradford method.
Two-dimensional gel electrophoresis: Isoelectric focusing (IEF) was done using the in-gel rehydration method (Bio-Rad, USA).
2D gels were analysed using PDQuest Advanced software (version 8.0) (Bio-Rad, USA). After acquisition, the images were analyzed using step-wise spot detection and spot matching followed by differential expression analysis. The quantity of each spot was normalized by total valid spot intensity. The expression differences for all four mycobacterial isolates were compared using the same software. Images for sensitive and resistant isolates were manually checked for artifactual spots, merged spots and missed spots, and spots with more isolate-specific variability were omitted in the downstream processing. Equal amount of protein was loaded in all gels and experiments were repeated three times with three independent biological replicates.
In-gel digestion of protein spots with trypsin: Protein spots of interest were excised from the coomassie brilliant blue R250 stained 2D gels using spot picker Investigator ProPic (Genomic Solutions Ltd., Huntingdon, UK). Digestion of proteins and spotting of peptides on matrix assisted LASER desorption/ionization-time of flight (MALDI-TOF) target plate was carried out using protein digester investigator ProPrep (Genomic Solutions, Huntingdon, UK).
For protein digestion, method of Shevchenko et al was followed with slight modifications. In brief, the gel plugs were de-stained and dehydrated by washing three times (10 min) with 25 mM NH4HCO3-50 per cent acetonitrile (ACN) (1:1v/v) solution and treated with freshly prepared 10 mM dithiothreitol (DTT) in 50 mM NH4HCO3 for 45 min at 56 C. After incubation, DTT was replaced with freshly prepared 55 mM iodoacetamide for 30 min and then dehydrated with 100 per cent ACN. The dried gel pieces were incubated for 12 h at 37 C with 25 mM NH4HCO3 containing 0.02 mug/mul of mass spectrometry grade trypsin (Promega, USA). The resulting peptides were extracted twice from the gel pieces, using peptide extraction buffer [1:1v/v mixture of 70% ACN and 0.1% trifluoroacetic acid (TFA)].
Mass spectrometric analysis: Mass spectrometry (MS) was carried out as described earlier. The digested samples were desalted and concentrated on C-18 ZipTips (Millipore, USA) using the manufacturer's protocol before mass spectrometric analysis. ZipTips were eluted on MTP 384 target plate with 2 mul of alpha-cyano-4-hydroxycinnamic acid (HCCA) (Sigma-Aldrich, USA) saturated solution dissolved in 50 per cent ACN and 0.2 per cent TFA. Mass spectra of digested proteins were acquired using Autoflex II TOF/TOF 50 (Bruker GmbH, Leipzig, Germany) in positive reflectron mode. AnchorChip target plate was placed in sample inlet of the instrument, controlled by flexControl 2.4 software (Bruker, Germany). The instrument was equipped with a 337 nm nitrogen LASER, delayed extraction electronics, and a 50Hz digitizer and percentage of LASER energy was maintained at 30-40 per cent. The pulse energy was 105 microJ and pulse duration was 1.3 nano sec. Final mass spectra were produced by averaging 1500-2500 LASER shots taken at different positions within each spot. The spectra were acquired in positive reflection mode in the mass range of 500-3000 m/z. Calibration was performed using peptide calibration standard II (Bruker, Germany). The proteolytic masses obtained, were processed through FlexAnalysis v.2.4 programme (Bruker, Germany) for peak detection. Initially, the spectra acquired were processed for baseline subtraction with 80 per cent baseline flatness followed by smoothening with threshold of signal-to-noise ratio (S/N) >5. The contaminant m/z peaks originating from human keratin, trypsin auto-digestion and matrix were removed from the spectra to generate the peptide mass list for the database search. Finally, the proteolytic masses obtained were evaluated using MASCOT, a peptide mass fingerprinting (PMF) tool (Matrix Sciences, UK). Peak detection in MALDI spectra and peak lists were submitted to the UniProtKB/Swiss-Prot database using the MASCOT search engine (http://www.matrixscience.com ) to identify the proteins from the annotated Mtb chromosome (strain H37Rv, EMBL/GenBank/DDBJ entry AL123456). Peptide mass tolerance was set in range of 50-100 ppm, with carbamidomethyl-cystein set as fixed modification, oxidation of methionine as variable modification and only 0 or 1 missed cleavage site was allowed. Further, matched precursor ions of identified proteins were selected for subsequent fragmentation using post source decay (PSD) for MS/MS. Lift_ATT method was performed in flex control software; parent peak mass spectrum was acquired by hitting LASER for 400-550 shots followed by acquisition of fragments of selected precursor ions for the same number of shots. Both parent and fragment spectra were pooled to generate MS/MS spectrum of a particular peptide. MS/MS spectrum was submitted to database using MASCOT wizard (Matrix Sciences, UK). The same parameters were used for MS/MS search in addition to the fragment mass tolerance from 0.5 to 2.0 Da.
Glycogen estimation: Logarithmic and stationary phase growth of Mtb sensitive (isolate A) and MDR (isolates B,C,D) isolates were collected by centrifugation (3 min at 5000 x g and at 4 C), and the pellet (15-20 mg wet weight) was re-suspended in 0.25M Na2CO3 and incubated at 95 C for 4 h. The glycogen content was estimated by following the procedure of Schulze et al.
Isolation of Mtb total RNA and real-time quantitative PCR (qRT-PCR): Mtb H37Rv was grown in Middlebrook 7H9 broth containing 10 per cent OADC, and was treated with INH (0.1microg/ml), RIF (1.0microg/ml), EMB (5microg/ml) and INH (0.1microg/ml) +RIF (1.0microg/ml). Total RNA was isolated using a TRI reagent (Sigma, USA) following manufacturer's instructions. To analyze mRNA expression, cDNA was synthesized from 1 microg of total RNA by using Superscript III (Invitrogen Life Technologies, USA) and random primers (Invitrogen, Life Technologies, USA), followed by amplification of the gene(s) by gene-specific primers, using master mix SYBR green (Applied Biological Materials Inc., Canada). The expression is represented in fold increase. 16sRNA was used as internal control for mRNA expression analysis of ahpC, Rv1827, pknA, pknB, pknG and wag31.
Each reaction was repeated thrice with three independent RNA samples in a smart cycler Cepheid machine (Cepheid, USA). RT-PCR conditions were as follows: an initial denaturation step of 10 min, followed by 40 amplification cycles of 30 sec at 95 C, 30 sec at 60 C and 30 sec at 72 C. Melting curve analysis was carried out to confirm the specificity of the amplified product. After baseline corrections and determination of threshold settings, calculation and statistical analyses were carried out using the 2- CT Method. The results are shown as fold increase in expression profile. | null | Not supported with pagination yet | null |
PMC3422143_01 | Male | 56 | A 56-year-old man was referred to our hospital with blurred vision in his right eye in April 2008. On initial examination, his corrected visual acuity was 20/20 in both eyes. The anterior chamber was mildly inflamed, but dense vitreous opacities were present in his right eye and optic neuritis was present bilaterally (Figure 1A and B). Fluorescein angiography showed dye leakage from both optic discs (Figure 1C and D). The results of laboratory examinations were essentially normal, including serum levels of angiotensin-converting enzyme, calcium, gammaglobulin, anti-human T lymphotropic virus-1 antibody, anti-herpes simplex virus antibody, and anti-varicella zoster virus antibody. The patient was weakly positive for tuberculin. A chest x-ray did not show bilateral hilar lymphadenopathy. Examinations according to the criteria for sarcoidosis were negative and tuberculosis was ruled out by our Department of Internal Medicine. His visual acuity had decreased to 20/100 OD, with increased numerous snowball-like vitreous opacities, and mutton-fat keratic precipitates and nodules were observed in the anterior chamber angles. Therefore, he underwent pars plana vitrectomy with a 25 gauge system to remove the dense vitreous opacities, and diluted and undiluted vitreous was obtained to determine the cause of the inflammation. Histiocytes, and epithelioid and multinucleated giant cells were detected by cytology in diluted vitreous samples, but necrotic materials and malignant cells were not detected (Figure 2). He received systemic corticosteroid therapy, and 2 months after surgery, optic neuritis was reduced and his corrected visual acuity had improved to 20/20 OD. | cytology, papilledema, pars plana vitrectomy, sarcoidosis, vitreous | Not supported with pagination yet | null |
PMC3422143_02 | Male | 77 | A 77-year-old man was referred to our hospital with blurred vision in May 2009. He was diagnosed with lung small cell carcinoma in October 2008, and received chemotherapy from December 2008 at our Department of Internal Medicine.
On initial examination, his corrected visual acuity was 20/20 OD and 20/25 OS. The anterior chamber was not inflamed, but numerous snowball-like vitreous opacities, optic neuritis, and periphlebitis were observed in both eyes (Figure 3A and B). Fluorescein angiography showed dye leakage from the optic discs and along the retinal veins in both eyes (Figure 3C and D).
The results of laboratory examinations were essentially normal. Neuron-specific enolase, progastrin-releasing peptide, and markers of lung small cell carcinoma were normal in the serum. The patient was weakly positive for tuberculin. A chest x-ray did not show bilateral hilar lymphadenopathy. A computed tomography scan of the chest showed that the original focus of the lung small cell carcinoma had disappeared after chemotherapy. Cerebral magnetic resonance did not detect any abnormalities. Thus, the attending physician considered that the probability of metastasis was low. Examinations according to the criteria of sarcoidosis were negative, and tuberculosis was ruled out, as in case 1.
The vitreous opacities in both eyes had increased a month later, and his corrected visual acuity was reduced to 6/20 OD and 6/10 OS. Therefore, he underwent pars plana | cytology, papilledema, pars plana vitrectomy, sarcoidosis, vitreous | Not supported with pagination yet | null |
PMC3279325_01 | Male | 69 | A 69-year-old man presented with recurrent bilateral pleural effusions of unclear etiology. He had undergone thoracocentesis more than 25 times over the last 2 years and had bilateral pleurodesis multiple times without success. Pleural fluid studies and a pleural biopsy were negative for malignancy or infection. He had no history of chest trauma, thoracic surgery, tuberculosis, lymphoma, cancer or significant exposure to asbestos. His renal, hepatic and cardiac function had been normal. He had smoked one-half pack cigarettes a day for 40 years and quit a year ago. He reported a chronic cough, exertional dyspnea, severe anorexia and weight loss of 30 kilograms in last 3 months. Due to his intractable pleural effusions of undetermined etiology, he was admitted for a lung biopsy and ligation of thoracic ducts.
The physical examination revealed a man with mild shortness of breath. He had generalized edema, decreased breath sounds over the lung bases and a normal cardiac examination. He was afebrile with normal respirations, a pulse of 86 beats per minute and blood pressure of 145/79 mm of Hg. White blood count was 8700 cells/mm3, hemoglobin was 10 g/dL, serum creatinine was 1.1 mg/dL and serum calcium was 8.8 mg/dL. Serum protein was 3.7 g/dL with albumin of 2.7 g/dL. Liver function tests were normal. Urinalysis showed 30 mg/dL protein in a spot sample. C-reactive protein was elevated at 50 mg/L. Anemia work up was consistent with anemia of chronic disease with normal serum B12 and folate levels. A chest x-ray showed bilateral pleural effusions. Echocardiogram showed normal left ventricular ejection fraction of 60% and there were no features of cardiac amyloidosis. Computed tomography of the chest and abdomen showed multiple calcified mediastinal lymphadenopathy and pleural effusions with atelectasis of the lung bases, but no obvious parenchymal lung lesions (Figure 1).
Pleural fluid was exudative with a white count of 212 cells/mm3 with 88% lymphocytes. Fluid triglycerides were elevated at 277 mg/dl, lactate dehydrogenase was 133 IU/L and fluid protein was 2800 mg/dL. The fluid was negative for infection, plasma cells or other tumor cells. Histopathology of biopsy of the right lung revealed pulmonary amyloidosis, mostly in a perivascular pattern, seen as hyaline deposits on Hematoxylin & Eosin stain (Figure 2). Apple-green birefringence was noted on Congo-red stain under polarized light. Mass spectroscopic subtyping revealed AL-kappa amyloid deposits.
Serum protein electrophoresis showed total protein of 3.3 g/dL with albumin 1.6 g/dL but absence of M-protein. Serum and urine immunofixation revealed presence of kappa free light chains. Serum free light chain analysis showed kappa free light chains of 47.2 mg/dL (ref 0.33-1.95 mg/dL) and a kappa to lambda light chain ratio of 41.4 (ref 0.26-1.65). Urine protein electrophoresis showed 24-hour urine protein of 1201 mg with M-protein of 40%. A bone marrow biopsy revealed 25% plasma cells comprised predominantly of kappa-expressing cells (Figure 3). A skeleton survey did not show any lytic or blastic lesions.
Our patient met the diagnostic criteria for MM based on bone marrow biopsy showing more than 10% plasma cells, monoclonal protein in the serum and urine, and presence of a myeloma-related organ dysfunction in the form of anemia. The etiology of his intractable effusion was felt to be pulmonary amyloidosis secondary to multiple myeloma. He did not have features of amyloidosis elsewhere such as cardiac failure, hepatomegaly, nephrotic syndrome and peripheral neuropathy. He was started on melphalan and bortezomib. His pleural effusions persisted despite thoracic duct ligation. His hospital course was complicated with acute renal failure, severe anasarca, deep vein thrombosis, congestive heart failure, myocardial infarction and sepsis. The diagnosis of MM as the cause of his intractable pleural effusion was terminal as the patient expired within a few weeks of diagnosis. | null | CT chest showing bilateral pleural effusions and clear lung parenchyma. |
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PMC6348547_01 | Male | 24 | A 24-year-old man had been diagnosed with rapidly progressing limited systemic sclerosis at the age of 19 years. He was under the care of a quaternary centre and was awaiting stem cell transplantation for systemic sclerosis. He suffered with spontaneous ulceration of digits and feet and had several small areas of ulceration at the time of injury. He also had reduced exercise tolerance and gastroesophageal reflux, but no other manifestations of systemic sclerosis. At the time of presentation, his regular medication included: omeprazole; mycophenelate mofetil; sildenafil; and nifedipine.
The patient suffered approximately 6%TBSA mixed depth flame burns to the right leg, following ignition of petrol used as an accelerant for a bonfire. This included areas of deep partial-thickness burn, totalling approximately 2%TBSA. Immediate first aid was applied with cool water for up to 1 h, before ambulance transfer to a local emergency department. Following analgesia, cleaning of burns and temporary dressing with sterile cling film, he was transferred to a UK regional burns unit. On assessment, the patient reported a pain score of 8/10 and it was observed that the burn involved areas of previous lower limb ulceration (Figure 1).
Treatment options were discussed with the patient. He expressed a desire to have enzymatic debridement. At approximately 12 h after the burn, the pre-treatment soak was commenced, following a local treatment protocol. At approximately 16 h after the burn, the patient underwent spinal anaesthesia. A total of 7 g of Nexobrid was reconstituted and applied to the burn wound in the operating theatre. Clear film dressings were applied with rolled paraffin gauze at the edges (Figure 2) and the patient was returned to the ward. Pain scores were in the range of 4-6 out of 10 following Nexobrid application, with patient-controlled analgesia in addition to the spinal anaesthetic. Four hours later, the patient was returned to theatre where, under mild sedation, the Nexobrid was removed and immediate burn reassessment was undertaken (Figure 3). Sterile saline-soaked gauze was applied with continuous saline irrigation via Foley catheter directly into the gauze dressings used for the following 12 h. During this time, pain scores were in the range of 3-6 out of 10.
Following liaison with Rheumatology, mycophenelate mofetil was discontinued. In addition, a course of iloprost infusions over five days were commenced. Dressings consisted of non-adherent silicone-based primary layers and sterile gauze. The patient was discharged from hospital at day 9 after the burn. Outpatient clinical review at day 25 revealed very small areas of over-granulation which were treated with topical steroid cream. Topical aqueous cream was applied to healed areas. At day 31 after the burn, all burned areas were fully healed (Figure 4). Scarring was minimal, the skin was soft and full, and pain-free range of movement was maintained. | nexobrid™, wound, burns, debridement, enzymatic, healing, impaired, microangiopathy, scleroderma | Not supported with pagination yet | null |
PMC8225978_01 | Female | 7 | A seven years old Saudi girl is known as a case of SCA. She presented to the emergency department with a history of fever for five days and jaundice with abdominal pain and mild respiratory distress. Also, she was complaining of left elbow pain for the preceding three days.
On examination, the patient was looking unwell, deeply jaundiced, highly febrile, with tachycardia and tachypnea. Blood pressure was normal. Chest examination revealed bilateral crepitation with bronchial breath at the base of lungs bilaterally. Cardiovascular system examination was normal. The abdomen was soft and lax with tender hepatomegaly while the spleen was just palpable. The left elbow was swollen with hotness and tenderness. No neurological deficits had been detected.
Initial workup showed :Hemoglobin: 7.5 g/dl, Mean Corpuscular Volume (MCV): 76 fL, White Blood Cells (WBC): 24 10^9/L, Platelets: 335 10^9/L, Prothrombin Time: 13 s., Partial Thrombotic Time: 33 s., Total Bilirubin (TB): 535 UMOL/L, Direct Bilirubin (DB): 434 UMOL/L, albumin: 24 G/L. Erythrocyte Sediment Ratio (ESR): 33 mm/hr. C-reactive protein (CRP):0.45. Chest X-ray revealed increased bronchovascular marking with bilateral basal lung opacities. | infective endocarditis, salmonella, salmonella entrica, sickle cell anemia | Not supported with pagination yet | null |
PMC7307403_01 | Female | 42 | The protocol described in this case report complies with standards of the Declaration of Helsinki and was approved by the Institutional Review Boards of participating institutions (IRB #16039-H29 and STU00203728) and met the Health Insurance Portability and Accountability Act (HIPAA) requirements for disclosure of protected health information. Written informed consent for participation was obtained from the patient's legal guardian.
The participant was a 42-year-old female who sustained a TBI from being struck by a motor vehicle at age 12. At study entry, she was 29.5 years post injury, dependent on caregivers for most ADL/instrumental activities of daily living (IADLs), used a manual wheelchair for mobility, resided in a group home setting, and required assistance from caregivers to help her make decisions. She attended an adult workshop where she would perform general fitness/mobility activities along with interacting with peers socially, and had done so for several years. As a result of her injury, she had abnormal tone, weakness and dysmetria/ataxia leading to decreased motor control and coordination of the right upper limb. She has avoided using her right (dominant) arm, which has led to learned nonuse of the right arm and overuse of the left arm. Furthermore, she had cognitive, short-term memory, and perceptual deficits. Right visual processing deficits made it difficult for her to read and distinguish color. Her mini mental state exam (MMSE) score at baseline was 15 out of 30. Due to these impairments, she did not spontaneously use her right upper limb functionally. Over the years since her injury, interventions including traditional physical and occupational therapy (functional mobility training, upper limb task practice, aquatic therapy provided by licensed therapists) have been implemented with limited success to increase the use of her right upper limb. | traumatic brain injury, motor learning-based therapy, myoelectric orthosis, orthotic devices, rehabilitation, robotics, upper extremity | Not supported with pagination yet | null |
PMC4247148_02 | Female | 6 | The patient was discharged after a 7-month period of hospitalization, which required maximal assistance in mobility, self-care, and cognition domains as measured with the Functional Independence Measure for Children. For her outpatient rehabilitation, we arranged fixed physical, occupational, and speech therapists with whom she was familiar, and we placed her in an isolated setting to avoid distracting stimuli that might deteriorate her attention span, emotional status, and behavioral outbursts. At 12 months after the onset of symptoms, she had merely achieved the developmental age of 6-8 months in terms of gross-motor and fine-motor milestones and 9-12 months in terms of cognition. She could obey some simple verbal orders but was mute most of the time, with cognitive deficits considered to be the main cause. Over the next 6 months, sequential programs such as toy-based training for postural control, imitation learning, matching training, and treadmill ambulation with partial body-weight support produced significant improvement. Her gross-motor skills progressed to the developmental milestone of 24-27 months, her fine-motor movements improved to 20-23 months, and her cognition advanced to 24-29 months. She could deal with simple self-care tasks, but occasional incontinence was still noted. She could speak more than five words and expressed herself correspondingly. The physical therapy with tricycle riding and balance-beam exercise continued according to the patient's tolerance.
In order to improve her cognitive deficits, psychological evaluation and training such as cognitive-behavioral therapy for attention, memory, and emotion regulation were added to her programs. The initial assessment for her intelligence quotient (IQ), measured by Wechsler Preschool and Primary Scale of Intelligence, was reported as mild mental retardation (full IQ =62), with performance IQ out of proportion to her scale in verbal IQ (scores were 58 and 71, respectively). | anti-nmda receptor encephalitis, autoimmune encephalitis, cognition deficits, rehabilitation | Not supported with pagination yet | null |
PMC6698273_01 | Male | 14 | A 14-year-old boy visited our hospital complaining of worsening left knee pain. He had twisted the left knee while playing basketball 18 months earlier. On physical examination, range of motion in the left knee was 0-140 . The patient showed tenderness on palpation along the lateral aspect of the joint line and a positive result for McMurray's test on the lateral side. X-rays revealed that growth plates on both the femur and tibia were still present. Magnetic resonance imaging (MRI) revealed a complete lateral discoid meniscus with degeneration within the meniscus (Fig. 1). The clinical diagnosis was complete lateral discoid meniscus, and the first arthroscopic surgery was performed. Complete lateral discoid meniscus with a radial tear was confirmed on arthroscopic examination (Fig. 2a), and partial meniscectomy was performed (Fig. 2b). No other abnormalities were noted. Partial to full weight-bearing was allowed as tolerated without immobilization of the knee, and physiotherapy including active motion exercises and thigh muscle strengthening started on postoperative day 1. After arthroscopic surgery, pain in the left knee improved, and the patient returned to playing basketball 5 months after the surgery.
At the 7-month follow-up, the patient revisited our hospital complaining of left knee pain and left knee locking developed during daily activity. No history of recent trauma was elicited. His height had increased 2.4 cm since the first surgery. On physical examination, range of motion in the left knee was 0-130 , with a positive result for McMurray's test of the lateral side. MRI revealed a low-signal cord between the anterior and posterior portions of the lateral meniscus, resembling a bucket handle tear of the lateral meniscus. A second arthroscopic surgery was performed based on these findings. During arthroscopy, we found that the anterior and posterior horns of the lateral meniscus were connected by meniscus-like tissue forming a ring-shaped meniscus (Fig. 2c). The newly formed interhorn meniscal bridge had not been present at the first surgery, and was thus suspected to represent the cause of the new knee pain. As a result, this bridge was resected. The posterior potion of the lateral meniscus was sutured with FAST-FIX360 (Smith & Nephew, Andover, MA) after identification of a longitudinal tear with instability. Full weight-bearing was started immediately, but knee flexion was limited to 90 for the first 3 weeks. Six months after the second arthroscopic surgery, the patient returned to playing basketball without any symptoms.
Hematoxylin and eosin staining of the newly formed interhorn meniscal bridge showed areas of chondrocyte-like cells mixed in collagenous fibers (Fig. 3a), with capillary vessels infiltrating the region (Fig. 3b). The newly formed interhorn bridge could thus have represented a meniscus-like tissue that appeared secondary to tissue repair.
One year after the second arthroscopic surgery, at 16 years old, the patient visited our hospital with right knee pain after stumbling on some stairs. Although the growth plates on both femur and tibia had closed, physical examination and MRI indicated complete discoid lateral meniscus similar to that in the left knee. Arthroscopic partial meniscectomy was performed. Currently, as of two years after the right knee surgery and three years after the second surgery on the left knee, the patient remains asymptomatic. Recent follow-up MRI of both knees has not shown any morphological changes.
Written informed consent was obtained from the patient and his family for publication of this case report and accompanying images. | arthroscopic meniscectomy, case report, discoid meniscus, knee, ring-shaped meniscus | Not supported with pagination yet | null |
PMC4927216_01 | Female | 58 | A 58-year-old diabetic woman was admitted to emergency department with unstable angina. After initial medication with acetylsalicylic acid, clopidogrel, enoxaparin, atorvastatin, ramipril, and pantoprazole, she underwent coronary angiography which revealed 90% stenosis at circumflex coronary artery and obtuse marginal branch of circumflex coronary artery (CX-OM) bifurcation (Medina 1-1-1) (Figure 1). A 7 F Extra BackUp guiding catheter was used to engage the left main coronary artery. Both the main branch and the side branch were wired. The obtuse marginal branch (OM) was dilated with a 2.0 x 20-mm balloon dilatation catheter (Simpass; Simeks, Istanbul, Turkey) at 16 atm, and the circumflex coronary artery (Cx) body was dilated with a 2.5 x 20-mm balloon dilatation catheter (Simpass; Simeks) at 18 atm. Thereafter, while parking a balloon in the main branch, a 2.5 x 18-mm stent (Endeavor Resolute; Medtronic) was deployed in the side branch at 12 atm and postdilated with a 2.5 x 12-mm noncompliant (NC) balloon (Simpass; Simeks) at 20 atm. Subsequently deploying the main branch balloon, a mini crush was performed and another 2.5 x 30-mm stent (Endeavor Resolute; Medtronic) was implanted at 20 atm into the Cx body. The OM was rewired and final kissing was performed with NC balloons. Thereafter, localized haziness suggesting thrombosis at first sight appeared in the main-branch stent, both in the proximal part and distal to the OM take off (Figure 2). The patient had no symptom and was hemodynamically stable. StentBoost showed stent fracture and disruption (Figure 3). Another Endeavor Resolute stent was implanted at 14 atm to cover the fracture sites. The final result was satisfactory (Figure 4). | stent fracture, stentboost, drug-eluting stent, percutaneous coronary intervention complications, stent restenosis, zotarolimus-eluting stent | Not supported with pagination yet | null |
PMC8046466_02 | Male | 14 | A 14-year-old male high school basketball player presented complaining of 2 weeks of right knee pain that began after mild trauma. Imaging revealed a lytic lesion within and crossing the distal femoral epiphysis, below the articular surface of the medial trochlea. Needle biopsy confirmed diagnosis of chondroblastoma. Full-length lower extremity X-ray revealed a leg length discrepancy of 4 mm, right longer than left. He underwent excisional curettage of the lesion with arthroscopic assistance, followed by fat grafting in attempt to prevent physeal bar formation. Surgery proceeded according to the two-portal technique, as described above (Fig. 4). The laterally based physeal tunnel was created distal to the physis, which served as the viewing portal. The working portal was a medially based tunnel, through which instruments were inserted. This two-tunnel technique provided minimal disruption to the physis, while facilitating "real-time" visualization of the excision (Fig. 5). After curettage, fat autograft was inserted into the defect to prevent physeal bar formation. The patient is 12 months from surgery with normal range of motion and function and no evidence of local recurrence. | chondroblastoma, arthroscopy, bone tumor, dry arthroscopy, orthopedic oncology | Not supported with pagination yet | null |
PMC7750352_01 | Male | 15 | A 15-year-old male patient presented to an external center with headache and swelling that started in his left eye and occurred in his right eye and forehead on the next day. The laboratory tests performed in the external center showed a white blood cell (WBC) value of 15 600/mm3 and a C-reactive protein (CRP) value of 5.6 (normal: 0-0.5) mg/dL. A diagnosis of acute frontal sinusitis was made with an examination and the laboratory findings, and oral amoxicillin-clavulanate treatment was initiated at a dosage of 60 mg/kg/day. Netilmicin sulfate eye drops and sodium fusidate ophthalmic ointment treatment was initiated because of conjunctivitis. The patient, whose headache and swelling in the left eye and forehead continued during treatment, presented to our hospital when his symptoms did not regress.
At the time of presentation, the patient's vital findings were as follows: body temperature: 36.8 C, blood pressure: 110/70 mm Hg, apical heartbeat: 74 beats/min. On physical examination, his oropharynx was hyperemic, there was periorbital edema and 2x2 cm of local swelling infraorbitally, hyperemia and local increase in the heat (Fig. 1a). There was marked postnasal purulent discharge and tenderness on the frontal region with palpation. The initial laboratory findings were as follows: WBC: 8.99 (74.5% neutrophil, 16% lymphocyte, 7.7% monocyte), hemoglobin (Hb): 15 g/dL, hematocrit (Hct): 42.2%, mean corpuscular volume (MCV): 92.9 fL, platelets (Plt): 333 000, CRP: 102 (normal: 0-8) mg/dL, erythrocyte sedimentation rate (ESR): 52 mm/h. Routine biochemical tests were found to be normal.
Treatment with intravenous ceftriaxone (75 mg/kg/day) and teicoplanin (a loading dosage of 16 mg/kg/day on the first day and a maintenance dosage of 8 mg/kg/day subsequently) was initiated with a prediagnosis of Pott's puffy tumor as a complication of frontal sinusitis. The paranasal sinus CT revealed increased mucosal thickness and appearance of a collection and a sclerotic lesion (osteoma?) in both frontal sinuses (with a size of 42x28 mm with lobulated contours in the widest part in the coronal plane extending to the left ethmoid cells on the left side), and an erosion in the anterior wall of the frontal sinus adjacent to the lesion described (Fig. 1b). On the second day of hospitalization, the patient was consulted by Opthalmology and Otorhinolaryngology clinics. The opthalmology consultation resulted as follows: "Full vision, eye movements are free and painless in all directions, no cell was observed in the anterior camera on biomicroscopic examination and bilateral fundi are natural." The patient was assessed by the otorhinolaryngology department and it was thought that excision of the mass, which was thought to be an osteoma, would be appropriate, because it eroded the anterior wall of the frontal sinus, and the sinusitis that developed was complicated by the development of subperiostal abscess (Pott's tumor). In the follow-up, the edema around the patient's eye and forehead reduced, and his headache improved. He was discharged with oral antibiotherapy after treatment with IV ceftriaxone and teicoplanin for 10 days. Following outpatient follow-up with antibiotherapy, the patient was hospitalized by the otorhinolaryngology department for surgery, mass excision was performed, and a histopathologic examination of the tissue obtained was found to be compatible with osteoma. Written consent was obtained from the patient who participated in the study and from his family. | adolescent, pott’s puffy tumor, osteoma, paranasal sinuses | Not supported with pagination yet | null |
PMC4310058_01 | Male | 16 | A 16-year-old male presented for evaluation of an indentation of his right parietal skull. The patient had first noted the indentation 2 weeks prior with no recent change in size. He had been involved in a 4-wheeler accident 2 years before and was evaluated for a possible concussion during a football game about one and a half years prior to presentation. The patient described having occasional headaches, but had no local tenderness or other neurological symptoms.
On examination, the patient was noted to have a palpable defect and indentation of the right parietal bone. The overlying scalp was unremarkable and he was neurologically intact.
The patient's previous imaging was reviewed. The first study, from 2 years prior, showed a skull defect in the right parietal bone [Figure 1a]. The second and third computed tomography (CT) scans showed progressive erosion of the skull [Figure 1b and c]. The defect did not appear to involve the dura or scalp. A magnetic resonance imaging (MRI) was obtained and confirmed the localization of the lesion to the skull [Figure 1e-f].
Excision of the skull defect and right parietal cranioplasty with titanium plate was performed. The overlying tissue was grossly abnormal, measuring approximately 5 cm in diameter, and was removed en bloc. The underlying bone was thin and eggshell like with a trabeculated pattern, especially in the center. Peripherally, the bone was thickened with a sponge-like appearance. The abnormal tissue portion could be seen replacing the diploic space while leaving the inner and outer table intact at the periphery. The dura was not involved and was stripped from the bone and left intact. The abnormal bone was then removed and a mesh titanium plate was used to replace the cranial defect [Figures 1d and 3].
The patient tolerated the operation well and had no immediate operative or perioperative complications. The right parietal indentation was corrected and the patient was discharged on postoperative day 2.
On gross examination, the soft tissue lesion appeared rubbery, yellow, and avascular. The tissue consisted predominantly of dense fibrous tissue with a few foci of woven bone at the periphery adjacent to the eroded bone. Angulated spicules of bone were rare, some of which lacked osteoblastic rimming while others were rimmed. There was minimal inflammation. The final diagnosis was that of a benign fibro-osseous lesion most in keeping with a DF. The case was reviewed at the Mayo Clinic where it was felt to be an atypical FD. Conflicting pathology interpretations of these lesions is not uncommon. | desmoplastic fibroma, fibrous dysplasia, intraosseous, ossifying fibroma, skull lesion | Not supported with pagination yet | null |
PMC4967693_01 | Female | 80 | An 80-year-old woman was admitted with reported fever that started 12 days before with no associated symptoms. According to her medical history, she was diagnosed with a myelodysplastic syndrome (MDS) 8 years ago, which was effectively managed with erythropoietin. Seven years earlier, she was diagnosed with ulcerative colitis, treated with mesalazine 800 mg twice daily. Finally, a tuberculosis (TB) infection was reported more than 40 years before. A former urine examination had revealed a urinary tract infection (urinary culture with the presence of E. coli > 105 CFU susceptible to almost all antibiotics). She received amoxicillin/clavulanic acid for a week and subsequently ciprofloxacin, one week prior to her presentation to the emergency department, but fever failed to settle.
At presentation, her body temperature was 38.5 C and she was hemodynamically stable. She reported no cough, dyspnea, abdominal pain, diarrhea, or dysuria. She had no clinical signs indicating a respiratory, urinary, or abdominal infection while a systolic aortic valve murmur was present. Her ECG revealed a 1st-degree AV block and her chest X-ray showed a cavity at the right upper lung field. Her tests revealed anemia (HCT = 23%, HGB = 7.2 mg/dL), a low WBC count, an elevated ESR (>100 mm/h), and CRP = 71.4 mg/L (0.0-5.0 mg/L); thus, she received 1 RBC unit for treating anemia. Fever was initially considered as a symptom of a urinary tract infection, which did not respond to the antibiotic treatment per os, and therefore she was treated with intravenous meropenem. At the same time, the patient received multiple blood transfusions, due to the fact that she was not responding to erythropoietin.
Since fever was persisting even after antibiotic treatment, simultaneously further investigation was deemed necessary. The patient had a CT scanning of the chest and the abdomen. The chest scanning revealed a cavity at the right upper lung field, which was consistent with the history of the old TB infection and the chest X-ray findings. The abdominal scan did not reveal any significant findings apart from the presence of edema at the rectum (Figure 1).
Subsequently, the patient had a colonoscopy, which revealed a thickened fold of rectum mucosa and diverticulosis of the sigmoid with redness of the surrounding mucosa. The patient was treated for 12 days with meropenem before the colonoscopy and diverticulosis was excluded as the cause of pyrexia since her fever did not settle. However, the coexistence of diverticulitis in remission could not be excluded. A few days later, the biopsies from colonoscopy revealed a mild chronic, unspecific inflammation of the sigmoid and the rectum.
Awaiting the results of the biopsies, the patient had a gastroscopy, which only revealed a mild gastritis. The transthoracic cardiac ultrasound confirmed a mild aortic valve stenosis with no other findings indicating endocarditis; thus, we did not proceed to a transoesophageal echocardiogram (multiple blood cultures were all negative). A myelogramconfirmed the MDS, RARS type. Moreover, a full laboratory examination of the immune system was conducted (ANA, anti-dsDNA, anti-ENA, anti-RNP, anti-Ro, anti-La, anti-sm, C-ANCA, P-ANCA, anti-MPO, anti-PR3, and anti-CCP) as well as serum protein electrophoresis, right temporal artery biopsy, and investigation for possible relapse of the old TB infection (Mantoux, urine, gastric fluid, sputum and bone marrow Ziehl-Neelsen stain, and culture for beta-Koch). Pending the results, the patient was discharged with prescription for paracetamol to treat the fever.
A few days later, the patient was readmitted for a blood transfusion and she was still febrile. The results of the immunologic tests were inconclusive {ANA (-), anti-ENA (+), and anti-RNP (+)}; the serum protein electrophoresis and the temporal artery biopsy were negative and so were the tests for the reactivation of the old TB infection. The patient was evaluated by a rheumatologist who recommended treatment with 20 mg of prednisone daily. After 21 days, the patient remained febrile and thus underwent a gallium-67 scintigraphy searching for a hidden focus of inflammation. The gallium-67 scintigraphy revealed persistent diffuse concentration of the gallium in the ascending colon (Figure 2) at 24-hour imaging, in discordance with the colonoscopy (no signs of active inflammation at the ascending colon).
The gallium-67 diffuse uptake of the ascending colon remained stable at the repeated 48- and 72-hour imaging without any topographic change after the use of laxatives (Figure 3).
Considering the results of gallium-67 scintigraphy, colonoscopy, biopsies of rectum and sigmoid, and the absence of another diagnosis, the patient was started on 30 mg of prednisone daily with mesalazine, as treatment for active ulcerative colitis. At the same time, she was receiving isoniazid and rifampicin as prophylaxis for the old TB infection. Subsequently, the patient's condition improved markedly, the fever retreated, and the need for blood transfusions also substantially decreased. The patient was discharged. One month later, she was reevaluated with a gallium-67 scintigraphy, which was notably different, with total absence of gallium-67 concentration in the ascending colon (Figure 4).
The cortisone dosage was decreased and close monitoring of the patient continued on an outpatient basis. | null | Not supported with pagination yet | null |
PMC9692072_01 | Female | 32 | A 32-year-old woman presented with acute-onset shortness of breath and chest pain for 4 days. She also complained of cough with some small amounts of phlegm and occasional low-grade fever, but no night sweat, rash, hemoptysis, loss of weight, joint swelling, or any other discomfort. Her medical history included hypotension, hypoglycemia and bile reflux gastritis. She was also a hepatitis B virus carrier and once arranged for an interventional operation for spontaneous intracerebral hemorrhage at the age of 20. Luckily, no sequela was found after that operation. Her home medications included itopride, sucralfate and famotidine. She was a lifelong non-smoker and had no history of recent travel, wild animal contacts or sick contacts. She lived in Guangdong province in China. She had no known allergies.
After admission to hospital, physical examination revealed the following: blood pressure was 92 mmHg systolic and 65 mmHg diastolic, respiratory rate was 21 breaths/min, heart rate was 122 beats/min, body temperature was 99.7 F, arterial oxygen saturation on room air was 95%. She had coarse breath sounds on auscultation without any wheezing, rhonchi or crackles. The remainder of the physical examination produced normal results.
Laboratory results suggested white blood cell count of 14,360 cells/mm (3) [normal value, 3,500-9,500 cells/mm(3)], neutrophil count of 10,820 cells/mm(3) [normal value, 1,800-6,300 cells/mm(3)], lymphocyte count of 1,960 cells/mm(3) [normal value, 1,100-3,200 cells/mm(3)], monocyte count of 850 cells/mm(3) [normal value, 100-600 cells/mm(3)] and procalcitonin level of 0.594 ng/ml (normal value, < 0.1 ng/ml). Blood gas analysis, NT-proBNP, D-dimer, cardiac enzymes were normal. T-Spot test suggested positive while other blood tests showed negative for blood culture, cryptococcal antigen latex agglutination test, candida galactomannan antigen test, (1-3)-beta-D glucan antigen test, tumor-associated antigens and HIV antibodies. In terms of immune-related examinations, blood level of immunoglobulin G turned out 20.8 g/L, slightly above the normal value (8.6-17.4 g/L), while levels of immunoglobulin A, immunoglobulin M, immunoglobulin E, complement 3 and complement 4 were within normal range. Blood levels of 6 types of cytokines, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6, and IL-10 were also normal. Moreover, no abnormal results were obtained on lymphocyte subset counts test, anti-extractable nuclear antigen antibodies test, antinuclear antibody test and vasculitis-associated autoantibodies test. Sputum culture and an electrocardiogram showed no obvious abnormalities. Initial chest radiograph indicated bilateral pneumonia. The contrasted chest CT demonstrated a 4.0 x 3.6 cm non-uniformly enhanced middle mediastinal mass with compression of lower trachea and superior vena cava (Figure 1A). Enlarged intramediastinal lymph nodes were appreciated, as well as right middle lobar infiltration (Figure 1D).
To obtain an accurate diagnosis, bronchoscopy, bronchoalveolar lavage (BAL), conventional transbronchial lung biopsy (TBLB) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were performed on the 4th day of hospitalization.
Bronchoscopy revealed severe trachea compression stenosis caused by an extratracheal neoplasm anterior to the lower trachea (Figure 2A), along with bronchial inflammation and airway secretion. Mixed bacteria were found yet indistinguishable by BALF smear and BALF culture. mNGS of BALF detected T. marneffei with 15 sequence reads identified out of 84 total reads. TBLB showed acute inflammation, negative for Acid-fast, PAS and GMS stains, and no tumor cells were seen (Figure 3A). Whereas, with the technology of EBUS-TBNA, we were able to observe the ultrasonogram of the extratracheal neoplasm (Figure 2B) and obtain the needle aspirates of the mass. On the 9th day of admission, culturing on Sabouraud dextrose agar medium at 25 C confirmed T. marneffei in the biopsied mass with colonies showing characteristic red-pigmented fungal colonies from the needle aspirates (Figure 2D). Under the microscope, the mold form of T. marneffei was also observed in imprint smear obtained from cultured samples of needle aspirates at 25 C on the background of lactophenol cotton blue staining (Figure 2C). On the same day, histopathologic picture of needle aspirates demonstrated acute exudative inflammation and focal necrosis, where yeast cells with characteristic transverse septa were identified through PAS and GMS staining (Figures 3C,D). Based on the evidence above, we finally proved the diagnosis was acute Talaromyces marneffei mediastinitis.
We initially treated the patient with intravenous moxifloxacin (dose: 400 mg/d), but the broad-spectrum antibiotic seemed to make little effect on her. Her shortness of breath and chest pain continued, while the cough and fever were even exacerbated. We changed the treatment into intravenous amphotericin B deoxycholate (AmBd) (initial dose: 0.1 mg/kg/d) immediately on the day when the diagnosis was confirmed. However, the patient experienced hypotension (BP: 70/43 mmHg) and refused to continue the therapy after the first infusion. Therefore, on the 10th day of hospitalization, she was treated with inhaled AmBd (dose: 0.7 mg/kg/d). As expected, the patient's symptoms were gradually alleviated during the therapy. She was eventually discharged with imaging improvement (Figures 1B,E) after 2-week treatment of nebulized AmBd. At 3-month follow-up, the patient was still stable with subsequent therapy of oral itraconazole (dose: 400 mg/d) and CT scan uncovered significant improvement (Figures 1C,F). | ebus-tbna, hiv-negative, talaromyces marneffei, immunocompetent, mediastinal mass, mediastinitis, nebulized amphotericin b | Not supported with pagination yet | null |
PMC8024073_01 | Female | 49 | Our patient is a 49-year-old Hispanic immigrant female with a 24-year history of painful RAS in the oral cavity (Figure 1). Her symptoms were associated with nausea and odynophagia. She reports that the sores last approximately one week at a time and can present with as many as thirteen at a single time. There was never a period of time when she had not had an oral ulcer present for the past 20 years and often she would have an average of 5-6 oral ulcers at any given time. Within the past 20 years, she has seen many doctors before immigrating to the US, but it is unclear what kind of treatment she tried in the past and she never got a formal diagnosis of her problem as well. She has only been controlled with pain medication for symptom relief. She also reports a longstanding history of intermittent postprandial bloating and a history of constipation. She denies diarrhea, hematochezia, and personal or family history of colon cancer or gastric cancer. Other past medical history includes anxiety, history of stroke, and hypertension. Her anxiety is very well controlled. She denies drinking or smoking. Differentials such as lupus, Crohn's, ulcerative colitis, Behcet syndrome, HIV, deep mycosis, tuberculosis, syphilis, celiac disease, vasculitis, drug-induced injury (NSAIDs or alendronate), and genital ulcers were all considered. The patient had an extensive lab workup for her aphthous ulcers by her PCP (Table 1) including antinuclear antibody, tissue transglutaminase IgA, HIV 1&2 Ab, and HSV-1 IgM, which were all negative. HSV-1 IgG was positive, but the patient had received multiple courses of acyclovir without resolution of her symptoms. The nutrition panel revealed vitamin B and zinc deficiencies for which a three-month supplementation was given without improvement in her symptoms. Repeat vitamin levels were ordered, but the patient did not follow up. She was seen by a dermatologist who recommended triamcinolone paste to affected areas in her mouth without help. She was then referred to gastroenterology for further workup.
For her physical exam, oral cavity revealed normal lips, normal dentition, and occlusion; two aphthous ulcers on the right buccal mucosa, approximately 0.5 cm in size were seen. No drainage or purulent discharge was noted so the ulcer was not swabbed for examination. Other reviews of systems including skin, eye, lymphatics, cardiovascular, abdomen, thyroid, neurologic, and respiratory systems were all normal. Esophagogastroduodenoscopy was done and revealed erythematous gastric mucosa (Figure 2). The biopsy of this area was positive for H. Pylori infection and mild active chronic gastritis. She was then prescribed quadruple therapy consisting of a proton pump inhibitor, tetracycline, metronidazole, and bismuth subsalicylate. After completion of the therapy, she reported simultaneous resolution of RAS. H. pylori stool antigen was performed after completion of quadruple therapy and confirmed eradication. She was seen in follow-up five months later and denies the presence of RAS which has not happened for the last 20 years. | null | Not supported with pagination yet | null |
PMC5175025_01 | Male | 73 | A 73-year-old male patient consulted to our outpatient clinics with complaints of ever-increasing number of non-healing wounds with foul-smelling discharge. Skin wounds of the patient were firstly appeared on his hip five years ago, and became more numerous since then. Biopsy material obtained one year ago was evaluated as chronic granulomatous dermatitis. His personal medical history was unremarkable, while his two siblings died of tuberculosis, and his son was still receiving tuberculostatic therapy. On his dermatological examination, red-violet atrophic plaque lesions with irregular contours, and patchy areas of adhered yellow-brown crusts, and squamas localized on the frontal, parietal, temporal, and malar regions, nose, and left ear were observed. Seventeen- 18 plaque-shaped lesions measuring 2-15 cm in diameter with adhered brown crusts, and squamas, and also eroded areas 0.5 cm-2.0 cm in diameter localized as islets on the anterior, and posterior aspect of the trunk, also on both upper, and lower extremities were seen. In addition to eroded areas on similarly appearing plaque lesions localized on the gluteal region, an ulcerated lesion 4 cm in diameter, and 1-1.5 cm in depth striked our attention (Figure 1). Histopathological examination of the biopsy material revealed a large ulcerated area covered superficially with crusts, lymphocytic, and histiocytic infiltration, and giant cells within superficial, and middle layer of dermis, and granulomas more conspicuously on the periphery of the infiltrate (Figure 2).
Application of periodic acid-Shiff (PAS), and Erlich-Ziehl-Neelsen (EZN) staining couldn't detect any specific infectious agent. Laboratory analyses revealed anemia, hypoproteinemia, increased CRP, and sedimentation rate. With these clinical, and histopathological findings, the diagnosis of generalized lupus vulgaris was made. The patient with a 9 mm-PPD reaction size, but without systemic involvement received antituberculostatic treatment with 300 mg isonicotinic acid hydrazide, 600 mg rifampicin, 1500 mg ethambutol, and 3000 mg pyrazinamide for 2 months, then with 300 mg isonicotinic acid hydrazide, and 600 mg rifampicin for 4 months. At two months of the treatment, lesions regressed remarkably. At the end the sixth month all lesions healed with postinflammatory hyperpigmentation, hypopigmentation and/or atrophic scar (Figure 3). | cutaneous tuberculosis, disseminated lupus vulgaris, lupus vulgaris | Not supported with pagination yet | null |
PMC10328157_01 | Female | 51 | A 51-year-old female presented with abdominal pain, diarrhea, and weight loss for 4 years. The abdominal pain was localized to epigastric region, non-radiating, and not associated with meals. She had loose bowel movements on-and-off with bowel movements occurring approximately five to six times per day. Initially, the stool was watery and mucoid with no foul odor, and not tinged with blood. The patient had significant weight loss despite good appetite and adequate oral intake. There was no associated fever, sweating, evening rise of temperature, vomiting, jaundice, mouth ulcers, or joint pain.
Patient was diagnosed with generalized anxiety disorder and has been on treatment with selective serotonin receptor inhibitors. She had previously presented to a local hospital, where she was treated with triple therapy for Helicobacter pylori and vitamin D supplementation for a low vitamin D level. She had no significant surgical history.
During physical examination, the patient did not have a fever peripheral lymphadenopathy or skin discoloration. Upon palpation, the abdomen was soft and non-tender, and no palpable mass or organomegaly was present. The rectal examination was non-painful and revealed no palpable rectal mass. The hematological reports showed a hemoglobin level of 13.6 g/dL and a white blood cell count of 7400/mm3 with 57% neutrophils, 39% lymphocytes, and 3% monocytes. The patient had an elevated level of anti-cyclic citrullinated peptide (CCP) at 22.83 U/mL and an anti-nuclear antibody (ANA) level of 81.31 AU/mL. The liver and renal function tests were within normal limits.
The stool test for occult blood was negative, and both the serum and stool tests for H. pylori were negative. The stool and urine cultures showed no growth after 48 h of incubation, and no eggs or intestinal parasites were seen on stool microscopy.
Ultrasonography of abdomen and pelvis showed no abnormality. Chest X-ray did not reveal any fibrosis or cavitations. Tuberculin skin test (TST) was negative. Colonoscopy with biopsy showed multiple aphthous ulcers with normal intervening mucosa in terminal ileum suggesting CD (Figure 1). Biopsy specimens showed focal active neutrophilic inflammation with villitis on terminal ileum. CD was suspected and patient was treated with tapering dose of steroids for 3 weeks. However, patient's symptoms were not improving. Subsequently, a repeat TST was done that was positive with an induration of 27 mm diameter. On GeneXpert test, Mycobacterium tuberculosis was not detected. A repeat colonoscopy with biopsy was performed and specimen was sent for acid-fast bacilli (AFB) stain where M. tuberculosis was detected. The patient started on antitubercular therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol according to the national guideline of Nepal. Patient responded well to the antitubercular regimen leading to resolution of symptoms and weight gain. | crohn’s disease, acid-fast bacilli, colonoscopy, intestinal tuberculosis | Not supported with pagination yet | null |
PMC4324991_01 | Male | 98 | Cause and age of death. The age of death reported in 150 CTE cases ranged from 17 to 98 years old, with the median age of death falling in the range of 60 to 69 years. This represents an earlier average age of death compared to the general US male population age of death of 76.2 years. Of the CTE cases, 72.7% died before the age of 70. Of the 111 CTE cases that included cause of death, none listed CTE as cause of death. The majority of the CTE subjects died from natural causes; however, the prevalence of suicide (11.7%) and accidental deaths (17.5%) is much higher in the CTE population than in the general population (1.5% and 4.8%, respectively). The greater percent of suicides and accidental deaths in the CTE case reports thus far have likely contributed to the lower average age of death in this selected group.
Suicide and accidental death are a more recent observation reported in subjects with CTE, with all suicides and 70% of accidental deaths coming after 2002. Researchers have suggested that reported CTE related symptoms such as lack of impulse control, criminal and antisocial behaviors, and mood disorders may be associated with the increased prevalence of suicide and accidental deaths. A review by Iverson (2014), however, points out that suicide and accidental death have been reported more often in less advanced stages of CTE thereby suggesting that such behaviors may not be due to progression of CTE. Selection-bias due to the greater CTE reporting on high profile former football players who have committed suicide or died due to accidental death has contributed to a possible overestimate of this cause of death. Published reports have noted both individuals and families of players who have died by suicide or accidental death have been disproportionately more likely to participate in CTE brain donation programs.
Neuropathology. Despite the younger average age of death in the CTE population compared to the general population, the typical age of death of subjects diagnosed with CTE can be considered advanced; hence, the effects of other age-related neuro degeneration diseases must also be taken into account. The general pathological characteristics associated with CTE include macroscopic degenerative changes such as cavum septum pellucidum, generalized global atrophy, thinning of the corpus callosum, and ventricular dilatation. Neurofibrillary tangles similar to AD are seen but not the density of senile plaques which are generally observed in AD. Irregular, multifocal, and generally perivascular tau-immunoreactive neurofibrillary tangles (NFTs) are now considered a pathognomonic finding exclusive to CTE distinguishing it from other neurodegenerative diseases. Beta-amyloid (Abeta) deposits are only identified in about 40% of those found to have CTE, as compared to extensive Abeta deposits present in nearly all those pathologically confirmed to have AD.
Large population studies reviewing pathological findings in the general population have shown that neurodegenerative pathological changes similar to CTE can occur naturally with the aging process. In a post mortem study with a non-selected cohort of 2661 subjects, Braak et al. reported that 91.6% of the subjects over the age of 60 had evidence of neurofibrillary tangles (NFT). Braak et al. as well as others have reported tau pathology findings in much younger cases, albeit at much lower frequencies compared to elderly subjects. In addition to tau related pathology, abnormalities in the transactive response (TAR) DNA binding protein with molecular weight of 43-kDa (TDP-43) have also been observed postmortem in the brains of CTE cases. TDP-43 pathology is a proteinopathy similar to tauopathy that is commonly observed in other neurodegenerative diseases such as in frontotemporal lobar degeneration (FTLD) and ALS. The findings of natural age-related pathology including both tau and TDP-43 have been been commonly observed in elderly non-demented controls in a number of studies as well.
Age. Increasing age is also a major risk factor for other neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson Disease (PD), Lewy body dementia (DLB), and cerebrovascular disease (CVD). McKee et al. 2013 reported that the 20 oldest subject of their 68 CTE cohort also displayed CTE-related neurodegenerative changes consistent with AD, PD, and DLB among other diagnoses. Although the interaction between diseases is unknown, one cannot discount that the presence of a co-morbid condition may distort both the clinical and pathological picture associated with CTE. As stated previously, CTE shares numerous neuropathological abnormalities commonly associated with other neurodegenerative diseases. Consequently, it is unclear what is responsible for specific clinical changes currently attributed to pre-morbid CTE. Omalu et al. (2011) stated that caution should be exercised when diagnosing CTE in those over the age of 65 since normal age related changes in the brain, Alzheimer's disease, chronic ischemic changes and small vessel disease in the brain could lead to confusion with pathological CTE related changes.
Smith et al. has proposed the pathogenesis of CTE may be best described as an interaction between neuropathological changes due to head trauma and natural age related changes of the brain. The exact contribution of prior head trauma on the clinical and neuropathological changes currently associated with CTE remains unclear and clinical symptoms may be a consequence of multiple neurodegenerative conditions including CTE. Importantly, the presence of neurodegenerative changes is not always associated with clinical symptomatic presentation.
Blaylock and Maroon postulated that immunoexcitotoxicity is a central mechanism in the development of CTE. Based on this concept, microglia, which are activated following TBI, initiate injury response mechanisms resulting in the release of various cytokines, chemokines, reactive oxygen and nitrogen species as part of the innate inflammatory response. This is followed by a reparation and regeneration process:provided there is no recurrent blows to the head. With repetitive brain trauma, before the reparative process, immune mediators along with the traumatic release of excitatory intracellular glutamate can trigger a cascade of neuronal damage including dendritic retraction, synaptic injury, damage to microtubules, mitochondrial suppression and the over-production of tau. | null | Not supported with pagination yet | null |
PMC4324991_02 | Male | 18 | Omalu et al. (2011) observed in an 18-year-old former high school football player "none to sparse" neurofibullary tangles in the cerebral cortex, subcortical nuclei, and brain stem. However he did conclude there was sufficient evidence of CTE but described these pathological findings as "incipient CTE", and suggested such findings potentially represented an initial stage of CTE development. McKee et al. have described a CTE pathology staging system to standardize CTE findings. Stage I lists the earliest abnormalities observed for CTE as focal epicenters of pathological tau located in the frontal cortex. By contrast, in more advanced CTE Stages III-IV the neuropathology is characterized by less focal and more widespread distribution of pathological tau throughout the cerebrum, subcortical nuclei, brainstem, and spinal cord. These neuropathologies are typically observed in older CTE subjects. McKee et al. has also reported a correlation of greater neuropathologic changes with greater number of years played, thus suggesting more advanced CTE pathology is linked to increased exposure to head trauma, and exclusive to older age of death. Due to limited available data the natural progression of CTE is still unknown. Whether less-advanced cases of CTE reported in generally younger subjects would eventually progress to advanced neuropathologic findings associated with advanced CTE has not been documented. There are early reports that PET scanning for tau protein may be useful to determine premorbid CTE and could possibly be used to follow changes over time.
Apolipoprotein E. Apolipoprotein E (ApoE) allele is a well-known genetic risk factor for Alzheimer disease. Kutner et al. and Jordan et al. have also reported that the presence of ApoE4 allele is associated with worse cognitive deficits in patients following severe head injury. Data on ApoE genotype was available for 80 CTE cases, which represents the largest compilation of CTE ApoE genotype to date. A Chi-square goodness of fit test was used to compare ApoE genotype of this CTE population to the ApoE genotype of the general population (data adapted from Beydoun et al.). This analysis revealed no significant group difference between ApoE4 carriers in the CTE population and the general population (p = .26), suggesting that ApoE may not be a significant risk factor for the development of CTE. The result of this analysis is similar to findings by McKee et al. (2012) who also reported non-significant difference between ApoE genotype of the general population and the 68 cases of CTE in presented in their cohort. The non-random selection and incomplete data of all CTE subjects limits speculation as to the significance of these findings. Further comparisons are needed to investigate the differences between post-mortem ApoE genotype of CTE, mTBI survivors and the general population.
Substance abuse. Thirty cases (20%) out of 153 CTE cases reported a positive history of substance abuse, which is greater than the 7.7% reported by Comptom et al. for substance abuse in US adults over their lifetime. Cottler et al. (2011) reported that 52% of retired football players used opioids during their NFL career, of which 71% reported misuse. CTE researchers have noted that the clinical presentation of CTE may be distorted due to history of substance abuse. Research investigating neurodegenerative effects of substance abuse has shown that several commonly abused substances may potentiate the development of other neurodegenerative conditions. These changes can include tau pathology, activated microglia, neuronal loss, and white matter rarefaction. In fact, in addition to these non-specific neurodegenerative changes, abuse of some substances such as opiates and opioids may elicit pathology very similar to those observed in CTE. In their research detailing the postmortem findings of opiate and opioid abusers, Anthony et al. (2010) observed enhanced NFT and NT deposition in their drug user subjects when compared to normal age-matched controls. Notably, histopathological analysis revealed the enhanced tau pathologies observed in the drug users were analogous to the pathological tau found in AD and CTE, but as in the case of CTE, the distribution was determined to be distinct from classical AD progression. How substance abuse may influence, co-present, or alter the pathologies observed in CTE is unknown. Due to the limited number of CTE cases that include information about history of substance use/abuse as well as limited reporting on the extent of use/abuse, no conclusion can be made as to the presence and nature of an association between substance abuse and CTE.
CTE related clinical signs and symptoms. Due to a lack of consistent clinical data in the CTE case reports, this review did not specifically discuss the various premorbid clinical signs and symptoms reported with CTE. Reported CTE-related sign and symptoms include headache, difficulties with attention and memory, mood disorders, motor dysfunction and dementia. McKee et al. have proposed a classification system (Stage I-IV) correlating advanced clinical findings to the degree of expected post mortem neuropathologic changes found with CTE. (Table 5) For comparison, Table 5 includes the clinical symptoms of CTE as well as clinical symptoms of other common neurodegenerative conditions. This comparison demonstrates a significant overlap between signs and symptoms of CTE and other common neurodegenerative conditions. Based on this proposed classification it is difficult to distinguish symptomatic CTE from other neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and FTLD. Postmortem neuropathological assessment remains the standard for definitive diagnosis.
Table 5 also compares clinical findings currently attributed to CTE to common signs and symptoms seen with post-concussion syndrome (PCS). In most cases, signs and symptoms associated with a concussion resolve within 1-4 weeks. PCS is characterized by a protracted course following the incident of mTBI that may last months to years following injury. Reynolds et al. and others have demonstrated that over time therapeutic interventions, such as cognitive, visual and balance therapies can improve recovery rates in patients with persistent PCS. Based on McKee's proposed clinical classification, symptoms of PCS substantially overlap with incipient symptoms of CTE. But unlike PCS where symptoms continue well after an mTBI, CTE attributed clinical findings are generally recognized as having a latent asymptomatic period of years to decades between exposure to mTBI and CTE symptom onset. Additionally, CTE, once symptomatic, is generally thought to be progressive and does not resolve over time. Despite the differences in the general onset of these conditions, some researchers have reported PCS proceeding directly to pathologically diagnosed CTE, further skewing the clinical diagnosis of CTE.
Most cases of neuropathologically confirmed CTE have reported signs and symptoms of neurological decline prior to death. However, McKee et al. (2012) reported 11% of their CTE-positive cohort (n = 5) were asymptomatic for any neurological conditions. Asymptomatic presentation was reported as advanced as CTE Stage III where there is widespread NFT pathology and neurodegeneration. Although asymptomatic presentation of neuropathology such as in AD is common, it remains unclear why some pathologically diagnosed CTE subjects experience symptoms while others do not.
American football players. Of the 153 CTE cases, 63 had a history of participation in football, and the majority of football subjects played at the professional level. It is important to separate out this subgroup since former football players have dominated CTE in the modern era of CTE research. In the 2012 review of 68 cases of CTE, McKee et al. observed that pathological findings of CTE were significantly correlated to the number of years a subject participated in football. However, despite the professional levels making up the majority of CTE cases, high school football players have also been reported to have CTE in spite of their limited mTBI exposure period. Although several of the high school football players were found to have CTE decades after their participation in high school football, three of the seven high school football players found to have CTE died prior to the age of 20. Despite this, the average age at death for football players is similar to the overall CTE cohort: 69% of CTE football cases compared to 75% of the remaining cases died prior to age 70. There was, however, a substantially higher prevalence of suicide in football players compared to the rest of the CTE cohort (17.5% (n = 11) vs. 5.26% (n = 3)). Football players account for 79% of all suicides case reports.
It is unknown whether this finding indicates that suicide is an at-risk behavior specifically related to former football players or if it is due to the bias associated with case reporting. Iverson et al. (2014) has noted that between the years 1960 and 2007 there were only nine cases of suicide of all former NFL players, again providing evidence that recent selective case reporting limits assertions as to risk factors associated with CTE.
Prevalence of substance abuse in American football players (n = 9; 14%) was lower compared to the rest of CTE cohort (n = 21; 23%). The limited data collected on substance abuse in the CTE literature prevents us to draw any firm conclusion about the association between CTE and substance abuse. However, it is of interest that the reported prevalence of substance abuse in former professional football players with CTE is substantially less than the prevalence suggested by other studies exploring substance abuse in former football players. For example, in a study by Cottler et al. (2011), 52% of retired football players used opioids during their NFL career with 71% reporting misuse. What, if any, effect substance abuse contributes to CTE in football players remains unknown and requires further exploration.
Data on ApoE genotype was available for 53 out of the 63 football players (84.1%). A chi-square goodness of fit test was conducted to compare the prevalence of ApoE4 carriers in football mTBI subgroup with the general populations. The analysis revealed that the difference in frequency between the ApoE4 allele carriers in former football players with CTE and the general population was also non-significant (p = .56).
The data compiled in this review is considerably limited due to the inherent limitations associated with retrospective case reports used to study CTE for the last 80 years. Case reporting lacks consistency in the types of data reported in CTE cases, such as incomplete pre-morbid data and furthermore, CTE case reports are inherently subject to selection bias. Despite the many millions who have participated in contact sports and potentially suffered an mTBI, there are currently only 40 modern era CTE articles with 153 pathologically confirmed CTE cases reported.
Although CTE research is still in its early stages, especially with American football players, researchers are encouraged to move beyond case reporting. These pioneering reports suggest an association between chronic neurodegeneration changes and head trauma, but without prospective controlled studies definitive conclusions about the incidence, prevalence and associated risk factors cannot be drawn.
Based on this review, beyond a history of prior head trauma, no other evidence was found to be associated with CTE related brain changes. Other previously suggested risk factors for CTE, such as severity and frequency of pre-morbid mTBI, history of substance abuse, duration of play in a contact sport, underlying genetic factors or uniqueness of pre-morbid symptoms, cannot be meaningfully associated with CTE at this time.
Although prior head trauma has been considered a consistent risk factor for CTE, Hazrati et al. (2013) demonstrated not all of those with prior sports related head trauma will have later onset of neurological deficits or develop neuropathology associated with CTE. They observed that 3 out of 6 (50%) brains of former CFL athletes displayed CTE neuropathological abnormalities, although all 6 players had extensive histories of head injury. Both Omalu et al. (2011) and McKee et al. (2012) observed similar findings in their cases where 6 out of 17 (35.3%) and 17 out of 85 (20%) subjects, respectively, were found negative for CTE neuropathologies, despite histories of multiple mTBI. | null | Not supported with pagination yet | null |
PMC10009051_01 | Unknown | 45 | A 45-year-old, men who have sex with men (MSM) patient with no significant, past medical history presented with the complaint of one week's duration of abdominal pain and fever of later onset (Day 1). The patient reported a weight loss of 10 kg over the past two months but denied respiratory symptoms, such as cough, dyspnea, and sputum, and asthenia. Physical examination revealed body temperature 37.9 C, heart rate 125 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 95% on ambient air. Physical examination revealed normal lung sounds and no abdominal mass and tenderness. Laboratory tests revealed normal leucocytes (8200/muL) with lymphopenia (lymphocyte count 650/muL) and a low CD4 count (14/muL), anemia (hemoglobin 10.7 g/dL), thrombocytopenia (platelets 136,000/muL), hypoalbuminemia (albumin 2.7 g/dL), elevated lactate dehydrogenase (277 IU/L), C-reactive protein (29.41 mg/dL), serum beta-d-Glucan 127.6 pg/mL (positive >= 80 pg/mL), and 54,000 copies/mL of HIV viral load. Based on these findings, HIV infection was diagnosed. A chest x-ray and Chest computed tomography (CT) revealed multiple lung cysts, respectively (Fig. 1 (A), (B)). In addition, abdominal contrasted CT revealed multiple hypodense cystic lesions in the spleen (Fig. 2. (A), (B)). Pneumocystis jirovecii pneumonia (PCP)was diagnosed on the basis of chest CT findings and elevated beta-D-glucan, and a 21-day course of trimethoprim/sulfamethoxazole was administered (the trimethoprim component of 5 mg/kg per day was given three times daily). Initially, extrapulmonary tuberculosis and lymphoma were considered as the differential diagnosis of the splenic lesions. A QuantiFERON-TB Gold Plus test returned negative. An ultrasound-guided needle biopsy of the spleen was performed on Day 4, and histological analysis revealed infiltration of foamy macrophages without granulomatous inflammation and lymphoid cells (Fig. 3 (A)). Although gram staining and Auramine-rhodamine staining did not reveal any bacteria and acid-fast bacilli, respectively, Grocott's methenamine silver staining revealed spherical cysts compatible with P. jirovecii (Fig. 3. (B)). An immunofluorescence assay for P. jirovecii was also positive for the cysts (Fig. 3. (C)). Based on these findings, an extrapulmonary P. jirovecii infection of the spleen was diagnosed.(Fig. 4, Fig. 5).
The abdominal pain gradually resolved, and on Day 10, the fever resolved. On Day 11, antiretroviral therapy (ART) with tenofovir disoproxil fumarate/emtricitabine and dolutegravir were begun. Chest CT on Day 24 revealed a decrease in the number of lung cysts (Fig. 1. (H)). Abdominal contrasted CT performed on the same day revealed enlargement of the multiple cystic lesions in the spleen (Fig. 1. (I), (J)). On Day 25, the fever recurred. There was no onset of new symptoms, and laboratory tests revealed no new abnormalities. Blood cultures and mycobacterial blood cultures, which were done because bacteremia and disseminated Mycobacterium avium-complex infection were suspected, returned negative. IRIS associated with a splenic P. jirovecii infection was suspected because the splenic lesions had enlarged after the antiretroviral therapy was begun, no other cause of fever was able to be established definitively. A decision was made to carefully observe the recurrence of abdominal symptoms without resuming trimethoprim/sulfamethoxazole or starting any additional treatment. On Day 31, the fever resolved. Follow-up abdominal contrast CT on Day 36 revealed no change in the size of the splenic lesions from Day 24. Still, abdominal contrast CT on Day 61 demonstrated a decrease in the size of the lesions, and chest CT revealed nearly complete resolution of the lung cysts, confirming our suspicion of IRIS associated with a splenic P. jirovecii infection. The clinical course was not complicated with either splenic rupture or splenic bleeding. Follow-up was performed via regular clinic visits and monitoring clinical symptoms and laboratory data. No relapse of the splenic lesions was observed in the following, two years. | extrapulmonary pneumocystis jirovecii infection, hiv, iris, iris in splenic pneumocystis jirovecii infection, pneumocystis jirovecii, splenic pneumocystis jirovecii infection | (B): Chest CT on Day 1 revealed multiple, diffuse lung cysts. |
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PMC10009051_01 | Unknown | 45 | A 45-year-old, men who have sex with men (MSM) patient with no significant, past medical history presented with the complaint of one week's duration of abdominal pain and fever of later onset (Day 1). The patient reported a weight loss of 10 kg over the past two months but denied respiratory symptoms, such as cough, dyspnea, and sputum, and asthenia. Physical examination revealed body temperature 37.9 C, heart rate 125 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 95% on ambient air. Physical examination revealed normal lung sounds and no abdominal mass and tenderness. Laboratory tests revealed normal leucocytes (8200/muL) with lymphopenia (lymphocyte count 650/muL) and a low CD4 count (14/muL), anemia (hemoglobin 10.7 g/dL), thrombocytopenia (platelets 136,000/muL), hypoalbuminemia (albumin 2.7 g/dL), elevated lactate dehydrogenase (277 IU/L), C-reactive protein (29.41 mg/dL), serum beta-d-Glucan 127.6 pg/mL (positive >= 80 pg/mL), and 54,000 copies/mL of HIV viral load. Based on these findings, HIV infection was diagnosed. A chest x-ray and Chest computed tomography (CT) revealed multiple lung cysts, respectively (Fig. 1 (A), (B)). In addition, abdominal contrasted CT revealed multiple hypodense cystic lesions in the spleen (Fig. 2. (A), (B)). Pneumocystis jirovecii pneumonia (PCP)was diagnosed on the basis of chest CT findings and elevated beta-D-glucan, and a 21-day course of trimethoprim/sulfamethoxazole was administered (the trimethoprim component of 5 mg/kg per day was given three times daily). Initially, extrapulmonary tuberculosis and lymphoma were considered as the differential diagnosis of the splenic lesions. A QuantiFERON-TB Gold Plus test returned negative. An ultrasound-guided needle biopsy of the spleen was performed on Day 4, and histological analysis revealed infiltration of foamy macrophages without granulomatous inflammation and lymphoid cells (Fig. 3 (A)). Although gram staining and Auramine-rhodamine staining did not reveal any bacteria and acid-fast bacilli, respectively, Grocott's methenamine silver staining revealed spherical cysts compatible with P. jirovecii (Fig. 3. (B)). An immunofluorescence assay for P. jirovecii was also positive for the cysts (Fig. 3. (C)). Based on these findings, an extrapulmonary P. jirovecii infection of the spleen was diagnosed.(Fig. 4, Fig. 5).
The abdominal pain gradually resolved, and on Day 10, the fever resolved. On Day 11, antiretroviral therapy (ART) with tenofovir disoproxil fumarate/emtricitabine and dolutegravir were begun. Chest CT on Day 24 revealed a decrease in the number of lung cysts (Fig. 1. (H)). Abdominal contrasted CT performed on the same day revealed enlargement of the multiple cystic lesions in the spleen (Fig. 1. (I), (J)). On Day 25, the fever recurred. There was no onset of new symptoms, and laboratory tests revealed no new abnormalities. Blood cultures and mycobacterial blood cultures, which were done because bacteremia and disseminated Mycobacterium avium-complex infection were suspected, returned negative. IRIS associated with a splenic P. jirovecii infection was suspected because the splenic lesions had enlarged after the antiretroviral therapy was begun, no other cause of fever was able to be established definitively. A decision was made to carefully observe the recurrence of abdominal symptoms without resuming trimethoprim/sulfamethoxazole or starting any additional treatment. On Day 31, the fever resolved. Follow-up abdominal contrast CT on Day 36 revealed no change in the size of the splenic lesions from Day 24. Still, abdominal contrast CT on Day 61 demonstrated a decrease in the size of the lesions, and chest CT revealed nearly complete resolution of the lung cysts, confirming our suspicion of IRIS associated with a splenic P. jirovecii infection. The clinical course was not complicated with either splenic rupture or splenic bleeding. Follow-up was performed via regular clinic visits and monitoring clinical symptoms and laboratory data. No relapse of the splenic lesions was observed in the following, two years. | extrapulmonary pneumocystis jirovecii infection, hiv, iris, iris in splenic pneumocystis jirovecii infection, pneumocystis jirovecii, splenic pneumocystis jirovecii infection | Chest CT on Day 24 revealed a decrease in the number of lung cysts. |
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PMC5917533_01 | Male | 46 | A 46-year-old man presented with asthenia, nocturnal transpiration, weight loss (17 kg/3-months), dysphagia and compressive thoracic adenopathies (absent on the initial radiography and present on the computed tomography-scan 3-month afterward). Blood tests showed hepatic cytolysis and cholestasis. Serologies were negative for C-hepatits, HIV, Epstein-Barr, Parvo, HHV8 viruses and for bilharzias and leishmania. The serum angiotensin I converting enzyme (ACE) was elevated (88, normal value <68 IU/L) as well as calcemia, creatininemia and uremia. The QuantiFERON test and culture of a mediastinal compressive adenopathy specimen were positive for Mycobacterium tuberculosis. Granulomas were noted on the skin, mediastinal (with significant necrosis) and liver and minor salivary gland biopsies. Kidney biopsy was suggestive of IgA-glomerulonephritis. Treatment with isoniazid, rifampicin, ethambutol and moxifloxacin was started. Corticoids were added 15 days afterward. A labial minor salivary gland biopsy was made due to persistent hypercalcemia at 14 days after the beginning of antituberculosis treatment. The glandular lobules showed foci of lymphocytic infiltrate with several polymorphonuclear neutrophils and several epithelioid and giant cell granulomas, some pericanalar with edematous and incipient necrosis [Figure 1a and b]. The Ziehl-Neelsen stain did not show acid-alcohol-resistant bacilli (AARB). At 26 days after the beginning of the treatment, the patient showed no clinical complaints and calcemia was normal; at 1 year, the patient had recovered. | granuloma, labial, minor salivary gland, sarcoidosis, tuberculosis | Not supported with pagination yet | null |
PMC4681961_01 | Male | 56 | A 56 year old male without a past smoking history presented to the emergency department with upper respiratory symptoms, fevers, night sweats, urinary retention, and leg weakness. On admission, chest computed tomography (CT) with contrast demonstrated a right perihilar mass with mediastinal extension, prominent mediastinal and paraesophageal lymphadenopathy, and was negative for PE (Fig. 1). Based on focal neurologic findings, magnetic resonance imaging of the head/spine was performed and showed lesions consistent with metastatic disease. Because the clinical-radiographic diagnosis suggested metastatic carcinoma, bronchoscopy with EBUS-guided TBNA of the invasive mediastinal mass was performed. EBUS imaging from the right main stem bronchus demonstrated a mobile filling defect within the right pulmonary artery (Fig. 2) which was confirmed by Doppler (Fig. 3). These characteristics were consistent with a PE. A repeat chest CT with contrast confirmed an acute PE involving the right main pulmonary artery and bilateral segmental pulmonary arteries (Fig. 4). The patient was treated with the preferred anticoagulation in the setting of malignancy; subcutaneous low molecular weight heparin. Pathology from the TBNA biopsy was positive for primary lung adenocarcinoma and the patient was initiated on systemic chemotherapy. Follow-up CT angiogram 3-months later showed resolution of the PE and tumor response to chemotherapy. | ebus, endobronchial ultrasound, endobronchial ultrasound, pe, pulmonary embolism, pulmonary embolus, tbna, transbronchoscopic needle aspiration | Computed tomography of the chest without a pulmonary embolus obtained prior to the EBUS. |
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PMC4681961_01 | Male | 56 | A 56 year old male without a past smoking history presented to the emergency department with upper respiratory symptoms, fevers, night sweats, urinary retention, and leg weakness. On admission, chest computed tomography (CT) with contrast demonstrated a right perihilar mass with mediastinal extension, prominent mediastinal and paraesophageal lymphadenopathy, and was negative for PE (Fig. 1). Based on focal neurologic findings, magnetic resonance imaging of the head/spine was performed and showed lesions consistent with metastatic disease. Because the clinical-radiographic diagnosis suggested metastatic carcinoma, bronchoscopy with EBUS-guided TBNA of the invasive mediastinal mass was performed. EBUS imaging from the right main stem bronchus demonstrated a mobile filling defect within the right pulmonary artery (Fig. 2) which was confirmed by Doppler (Fig. 3). These characteristics were consistent with a PE. A repeat chest CT with contrast confirmed an acute PE involving the right main pulmonary artery and bilateral segmental pulmonary arteries (Fig. 4). The patient was treated with the preferred anticoagulation in the setting of malignancy; subcutaneous low molecular weight heparin. Pathology from the TBNA biopsy was positive for primary lung adenocarcinoma and the patient was initiated on systemic chemotherapy. Follow-up CT angiogram 3-months later showed resolution of the PE and tumor response to chemotherapy. | ebus, endobronchial ultrasound, endobronchial ultrasound, pe, pulmonary embolism, pulmonary embolus, tbna, transbronchoscopic needle aspiration | Computed tomography of the chest confirming the pulmonary embolus that was originally diagnosed by EBUS. |
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PMC9773200_01 | Male | 20 | A 20-years-old man presented with a new rash to his primary care provider in June 2020. He had been previously diagnosed with SCID-X1 due to hypomorphic interleukin-2 receptor subunit gamma-chain (IL2RG) mutation in 2017, approximately 3 years prior to the onset of his rash. His immunologic evaluation was undertaken due to a history of severe eczema and frequent infections as well as a family history of immunodeficiency. Immunologic work-up was initially notable for hypogammaglobulinemia and he was placed on standard monthly intravenous immunoglobulin (IVIG) infusions. Genetic testing then returned positive for the c.460C>T (p.P154S) mutation in the IL2RG gene. At the time of presentation, the patient reported a six-month history of hyperpigmented, violaceous macules and plaques involving the extremities and torso but sparing the palms, soles, and mucous membranes ( Figure 1 ). His skin lesions began on both feet and spread to the legs, torso, arms, and face over the course of a few months. At the time of initial evaluation, Tinea corporis was confirmed by potassium hydroxide preparation of a skin scraping, and flesh-colored papules with central umbilication clinically resembling those of molluscum contagiosum were also noted. Review of systems was negative for fevers, chills, arthralgias, respiratory, gastrointestinal, or genitourinary symptoms. Laboratory tests obtained eight months after appearance of the skin lesions were notable for a normal serum immunoglobulin G of 798 mg/dL and low CD4+ and CD8+ T-cell counts at 199 and <45 cells/microL, respectively. Very unusual for a SCID-X1 patient, he had above upper normal range numbers of CD3/CD16+56+ natural killer cells (1909 cells/microL, normal range 126-729 cells/microL). Prior to SCID-X1 diagnosis, he received routine childhood immunizations, including two doses of MMR vaccine at 1 and 4 years of age and a varicella vaccine. The patient reported two previous episodes of herpes zoster, persistent molluscum contagiosum, bacterial skin and soft-tissue infections, Tinea corporis, onychomycosis, and several episodes of viral and bacterial pneumonia. Prior to the onset of the skin lesions, he had no known exposure to tuberculosis or animal exposures. At the time of presentation, he was enrolled as a university student and lived with two roommates. During university breaks, he lived with his parents and a younger sibling, hereinafter referred to as close contacts.
The patient underwent biopsy of a violaceous macular lesion on his left flank. Dermatopathology revealed superficial and deep dermal infiltrates, predominantly histocytes, aggregating into poorly formed granulomas centered around vessels and adnexal structures. The Gram, Periodic Acid-Schiff, fluorescent rhodamine acid-fast, Fite, and Grocott methenamine silver stains were negative, as were fungal and mycobacterial cultures. Double fluorescent immunohistochemical (IHC) staining of formalin-fixed paraffin-embedded (FFPE) tissue sections of the skin biopsy with mouse monoclonal antibody against RuV capsid and rabbit polyclonal antibody against CD206 revealed the presence of RuV in M2 macrophages in the cores of granulomas located in the upper ( Figures 2A, C ) and deep dermis ( Figures 2B, D ). No staining for RuV capsid was detected in a few myeloperoxidase (MPO)-positive neutrophils near the granulomas (not shown). IHC staining for measles virus and varicella zoster virus (VZV) antigens were negative (not shown).
Following consultation with an infectious disease specialist, an NP swab and fresh-frozen skin biopsy sample were collected for the detection of RuV RNA by RT-qPCR in December 2020. RuV RNA was not detected in the skin biopsy sample. The failure to detect RuV RNA by RT-PCR in the fresh-frozen skin biopsy despite detecting RuV capsid by IHC in FFPE tissue sections is most likely due to the absence of RuV-positive cells in the frozen biopsy, as RuV is known to be unevenly distributed in lesions. However, RuV RNA was detected in the NP swab, and replication-competent RuV was isolated in Vero cell culture from the NP swab ( Figure 3 ). Because the patient had no known recent exposures to persons with suspected or confirmed rubella, there was concern that the RuV had been acquired earlier, potentially through MMR vaccination. The complete genomic sequence of the isolated virus was determined using the Sanger method and designated RVi/Oregon.USA/49.20 (GenBank accession number ON861827). Phylogenetic analysis showed that the isolated virus was vaccine-derived ( Figure S1 ) with 97.3% nucleotide identity to the genomic sequence of the RA27/3 strain used in an MMR vaccine. A 36-nucleotide deletion in RVi/Oregon.USA/49.20 resulted in the N-terminal deletion of 12 amino acids of the E2 glycoprotein. Despite this deletion, the virus replicated efficiently in Vero cells, producing titers around 106 focus forming units (ffu) per mL of the culture medium, which is 1-2 logs higher than those produced by other previously described VDRV isolates. Following these results, it was recommended that the patient adhere to droplet precautions until further information regarding potential VDRV shedding could be ascertained.
Treatment. No specific treatment is currently indicated for rubella virus infection. The progression of the rubella virus infection and waning immunity, as indicated by a decline in CD4+ and CD8+ T-cell numbers in the absence of available anti-viral therapy for rubella, provided the rationale for the patient to undergo ex vivo lentiviral gene therapy at the National Institutes of Health (NCT01306019) with busulfan (6 mg/kg total) myeloid conditioning in April 2021. In September 2021, approximately 5 months after gene therapy, the patient was admitted for facial rash and meningitis. A swab collected from a facial skin lesion was positive for VZV by PCR. Cerebrospinal fluid (CSF) was positive for VZV as well as for VDRV by RT-qPCR. VDRV viral load was 4.3x102 RNA copies/mL CSF; live VDRV was not recovered from CSF ( Figure 3 ). He received IV acyclovir 10 mg/kg every 8 hours for 10 days and IV hydrocortisone 50 mg daily for 3 days for VZV treatment during his hospital admission. He was discharged home on oral valacyclovir 1 g every 8 hours for 11 days to complete a total 21-day course of antiviral therapy, then transitioned to acyclovir prophylaxis.
At time of report, patient was 9 months post gene therapy and pancytopenic with absolute neutrophil counts in the range of approximately 500-1000 cells/microL. Reconstitution of T-cells in older X-SCID patients takes years and at this early time point, his T-cell counts remained low with a CD4 count of 65 cells/microL (21%) and CD8 count of <45 cells/microL (4.1%). However, his violaceous skin lesions had mostly resolved by 9 months following gene therapy.
A bone marrow biopsy performed in July 2022 to evaluate ongoing pancytopenia (WBC 1.34 K/microL, hemoglobin 9.6 g/dL, and platelet count 20 K/microL) was notable for the presence of multiple foci of granulomatous inflammation. Grocott methenamine silver and acid-fast bacilli stains did not detect fungal and mycobacterial organisms in the bone marrow biopsy. There was no evidence of Epstein-Barr virus on in-situ hybridization. Qualitative PCR for cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and adenovirus was negative. To evaluate the possibility of VRDV as a possible etiology of the patient's pancytopenia, the sequential tissue sections of bone marrow core biopsy were double immunostained with RuV capsid antibody and either CD206, MPO, or CD3 antibody ( Figure 4 ). The bone marrow was strongly positive for rubella capsid with MPO+ neutrophils being the main infected cells and almost all neutrophils were rubella-positive. There was heavy infiltration of CD206+ macrophages, many of them forming granulomas. Numerous CD3+ T cells were predominately localized inside the granulomas. The areas occupied by granulomas were free from rubella-positive neutrophils, but some macrophages inside the granulomas contained rubella antigen. In addition, macrophages with rubella-positive neutrophils or globules of rubella antigen inside the cells could be seen throughout the sample outside of granulomas. The lack of IHC staining of neutrophils and macrophages with VZV monoclonal antibody cocktail confirmed the specificity of rubella antibody staining of these cells (not shown).
To monitor virus shedding by this patient, 11 sequential respiratory samples (eight NP swabs, one nasal swab, two oropharyngeal swabs) and two urine samples were collected over 15 months beginning in December 2020. The samples were analyzed by quantitative RT-qPCR and viral cell culture. VDRV RNA was detected in all eight NP swabs; replication-competent viruses were recovered from six of these ( Figure 3 ). The amount of virus in the NP swabs varied between 4.3x101 to 4.3x102 RNA copies/mL of swab media with two spikes of RuV RNA concentration. One spike of 1.4x104 RNA copies/mL was observed three months after gene therapy in July 2021, and the second spike of 9.9x103 RNA copies/mL occurred in March 2022, four months after treatment with steroids. IVIG had been administered monthly during this period. Two oropharyngeal swabs, a nasal swab, and urine collected in July 2021, contained replication-competent VDRV as well. Only one urine sample and two NP swab samples were culture-negative, and each was collected at a different time point. Viral RNA loads in the culture-negative samples were compatible to those in the culture-positive samples.
Though VDRVs have been detected in some individuals with inborn errors of immunity by culture in skin lesions and by RT-PCR in NP swabs, and RuV vaccine has been hypothesized to be an antigenic trigger for development of cutaneous granulomas, transmissibility of VDRVs remains unknown. To assess potential transmission of VDRV from the patient to his close contacts, NP swabs and serum samples were collected from three close contacts in the family, including an immunocompetent adolescent sibling. NP swabs were tested by rubella RT-qPCR. Serologic investigation included measuring immunoglobulin M (IgM) and IgG to rubella virus, and 50% neutralization titer (NT50) against the RA27/3 rubella virus strain as previously described. The patient's rubella serologic status was also assessed. The NP swabs of these close contacts were negative by RT-qPCR. None of the serum samples contained rubella IgM. IgG titers of the close contacts ranged from 25-60 IU/mL, and the NT50 was 80 ( Supplementary Table 1 ); both results were similar to those of typical immunocompetent vaccinees. In contrast, the serum neutralization titer of the patient was substantially higher (NT50 = 640) than that of his close contacts or other immunocompetent vaccinees. Laboratory testing did not provide evidence of VDRV transmission to close contacts, including a younger sibling who could be potentially exposed prior to receipt of MMR vaccination, suggesting that VDRV is unlikely to have been transmitted to vaccinated contacts with competent immune systems. In light of these results, the infectious disease physician and public health officials advised the patient that the droplet precautions suggested earlier for infection control could be discontinued. | gene therapy, inborn errors of immunity, live virus shedding, skin granuloma, vaccine-derived rubella virus, viral persistence | Not supported with pagination yet | null |
PMC9807439_01 | Female | 29 | A 29-year-old woman, with no history of smoking and unremarkable medical history, reported to our hospital with the chief complaint of respiratory distress. The patient was diagnosed with right pleural effusion and a tumor in her right lung (Figure 1a-c). Enhanced brain magnetic resonance imaging (MRI) revealed multiple brain metastases. Her previous physician had performed thoracentesis and examined the pleural fluid, but found no evidence of malignant cells, after which she was referred to our hospital. On her first visit, a second pleural effusion test was performed, but no malignant cells were detected. Bronchoscopy was performed on the fifth day. On transbronchial biopsy (TBB), malignant cells were detected using rapid on-site evaluation (ROSE), and genetic analysis was performed on fresh-frozen specimen using the AmoyDx Pan Lung Cancer PCR panel (Amoy) (Amoy Diagnostics). However, histopathological analysis performed on the eighth day showed insufficient tissue specimen, and transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed on the ninth day. A paraoesophageal lymph node lesion was collected, and a sufficient number of malignant cells were detected using ROSE, but several necrotic components were also found. On the 12th day, histopathological analysis revealed that the EUS-FNA specimen also did not yield a sufficient amount of tissue, and thoracoscopy was performed under local anesthesia on the same day. During thoracoscopy, pleural fluid was submitted for third examination, but no malignant cells were detected. However, sufficient tumor tissue samples were successfully obtained via thoracoscopy. The course of these biopsies is summarized in Figure 2. On the same day, EGFR L858R mutation was detected by Amoy, and treatment with EGFR-tyrosine kinase inhibitor was initiated. Immunohistochemistry was performed on bronchoscopy biopsy specimens, wherein the tissue samples were stained with a specific antibody against EGFR L858R, which confirmed the presence of tumor cells (Figure 3). | gene panel, genomic biopsy, lung cancer, rapid on-site evaluation, thoracoscopy | Not supported with pagination yet | null |
PMC4140721_01 | Female | 41 | A 41-year-old woman was admitted to the local hospital in November 2011 because of a sudden onset of the left limb weakness which lasted for a few minutes. Brain computed tomography (CT) showed seven heterogeneous haemorrhagic lesions surrounded by edema. The lesions were spread throught both hemispheres - one in the right frontal lobe, one in the right parietal lobe, four in the left parietal lobe and one in the left occipital lobe (Figure 1A). Magnetic resonance imaging (MRI) confirmed the presence of multiple lesions which were surrounded by edema and contained hemosiderin deposits (Figure 1B). They also demonstrated predominantly central contrast enhancement. Those findings were suggestive of neoplasmatic metastases or vascular malformations. MRI angiography was performed. However, apart from hypoplasia of part A1 of the left anterior cerebral artery no other abnormalities were noted. Abdominal ultrasound as well as chest X-ray showed no significant changes. Erythrocyte sedimentation rate was slightly elevated (18 mm after one hour, normal range up to 15 mm). Adequate blood tests excluded the presence of antibodies against Borrelia burgdorferi in M and G classes. Moreover, the Candida, Cryptococcus and Aspergillus antigens were not detected in the serum. Only antibodies against Toxoplasma gondii in G class were positive. In December 2011 the patient was admitted to hospital again due to the right limb weakness. MRI revealed multiple lesions very similar to those reported in November 2011 (Figure 2A, 2B). Similarly to those in the previous study, they were surrounded with edema and showed central contrast enhancement. Chest X-ray was normal. Erythrocyte sedimentation rate was elevated up to 37 mm after one hour. Finally, the patient was qualified to a neurosurgical operation and in January 2012 the tumor from the right frontal lobe was removed. The histopathological assessment revealed hemorrhagic areas with calcifications.
In May 2012 the patient, because of the diagnostic problems, was admitted to the Department of Neurology, Medical University of Warsaw, for the first time. Neurological examination revealed a slight weakness of the right limbs and subtle superficial sensation impairment in the right limbs and chest. Routine blood tests showed anemia (hemoglobin level of 11.1 g%, normal range 12-16 g%), decreased vitamin B12 level (162.3 pg/ml, normal range 191-663 pg/ml) and increased erythrocyte sedimentation rate (33 mm after one hour, normal range up to 12 mm). MRI presented a slight reduction in the size of the lesion in the left parietal lobe. As previously, central contrast enhancement and edema were noted (Figure 3). Based on these findings, vascular abnormality was suspected and therefore digital subtraction angiography (DSA) was performed. However, it showed no abnormalities. Disseminated pathological discharges were detected on electroencephalography. The ophthalmological examination showed irregular deficits in the visual field. There were no symptoms or signs of endometriosis, which may rarely cause intracystic hemorrhages in the central nervous system. The lumbar puncture was performed, and apart from a slightly elevated protein level (62 mg/dl, normal range 15-45 mg/dl), the analysis of the cerebrospinal fluid (CSF) was normal. An additional CSF examination excluded tuberculosis, neuroboreliosis and Cryptococcus infection. The level of thyroid hormones, rheumatoid factor, antibodies against Borrelia spp. in the serum were within normal ranges. Furthermore, the presence of anti-neutrophil cytoplasmic antibodies, antinuclear and anticardiolipin antibodies, lupus anticoagulant, trombophilia, syphilis and HIV infection were excluded by appropriate tests. The antithrombin III level was within normal ranges. The computed tomography of the chest aroused a suspicion of an abnormal mass in the left atrium (Figure 4). Transthoracic echocardiography confirmed the presence of a floating and fragmented mass in the left atrium and based on that the atrial myxoma was recognized. The patient was transferred to the Department of Cardiosurgery and Transplantology, Institute of Cardiology, where at the end of May 2012, heart surgery was performed. Histopathological assessment confirmed the presence of atrial myxoma.
The patient was admitted for the second time to the Department of Neurology in July 2012. Neurological examination showed a slight weakness of the right lower limb and a discrete superficial sensory deficit in the right lower limb and on the left side of the chest. Laboratory tests revealed anemia with iron deficiency and appropriate treatment was introduced. MRI showed reduction in size of the lesion and decreased edema in the left frontal lobe. Other lesions had similar appearance to those previously described. Meanwhile, the histopathological brain sections were examined once again, and chronic inflammation and hemorrhagic process with hemosiderin-laden macrophages, and glial and mesodermal severe reaction with vessel and collagen fiber calcifications were found. There were no signs of fungal infection, neoplastic lesion or cerebral endometriosis.
The third hospitalization in the Department of Neurology took place in January 2013. The neurological examination was comparable with the previous one. The echocardiography showed no signs of myxoma recurrence. Abdominal ultrasound demonstrated no significant abnormalities. The ultrasound of thyroid gland disclosed nodular goiter. Antithyroid antibodies were not detected. MRI of the brain revealed lesions comparable to those already described (Figure 5). Partial resolution of edema surrounding brain lesions was seen on follow-up MRI in July 2013 (Figure 6A, 6B). However, central contrast enhancement was still present (Figure 6C, 6D). There were no new metastases. The neurological examination was similar to the one carried out six months ago. However, further observation and control investigations were recommended. | atrial myxoma, brain metastases, cerebral embolism, hemorrhagic brain lesions | Not supported with pagination yet | null |
PMC7983232_01 | Female | 52 | A 52-year-old woman of Cuban origin was referred to our clinic for skin hardening for over 15 years. Her past medical history was pertinent for mild asthma and severe glaucoma. On skin examination, there were three ill-defined indurated, depressed plaques measuring 10 cm x 15 cm on the left mid-back, 7 cm x 7 cm on the left posterior shoulder, and 15 cm x 3 cm linear induration extending to the left forearm (Figure 1(a) and (b)). Examination of the oral mucosa and genitalia was unremarkable. Workup, including complete blood count, chemistry, renal and liver function tests, borrelia serology, antinuclear, and systemic sclerosis specific antibodies, was normal, except for mild eosinophilia. A punch biopsy of the left upper back lesion demonstrated a normal epidermis and superficial dermis. There was non-inflammatory extensive sclerosis in the deep dermis, subcutaneous tissue, and fascia.
The diagnosis of linear localized scleroderma profunda versus eosinophilic fasciitis was made. Pre-treatment screening for hepatitis B, hepatitis C, human immunodeficiency virus, QuantiFERON-TB Gold, and strongyloides serology were performed and subsequently revealed the presence of strongyloides antibodies, which were confirmed by fecal culture. The patient was treated with oral ivermectin resulting in a resolution of her respiratory symptoms and normalization of the eosinophil counts.
After successful eradication of strongyloidiasis, we planned to initiate methotrexate monotherapy, which was delayed due to scheduled hysterectomy for uterine fibroids. When the patient returned to our clinic, a new linear depressed plaque on the mid-forehead was noted (Figure 1(c)). She also complained of worsened vision in the right eye and new-onset migraine-type headache. Given the typical clinical appearance of the forehead lesion, a diagnosis of ECDS scleroderma was made. She was referred to her treating ophthalmologist, and a magnetic resonance imaging (MRI) of the brain was ordered. The MRI showed no skeletal or parenchymal abnormalities. Ocular examination revealed stable glaucoma. Oral prednisone 1 mg/kg/day (tapered over 3 months) and methotrexate 20 mg/week with folic acid and vitamin D supplementation were prescribed with regular follow-up. After 3 months of therapy, the size and induration of the truncal plaques had improved (Figure 2(a) and (b)). The linear groove over her forehead remained stable (Figure 2(c)). No new episodes of migraine headaches have occurred. | scleroderma, adult-onset scleroderma, en coup de sabre scleroderma, linear scleroderma, localized scleroderma, morphea | Not supported with pagination yet | null |
PMC6475548_01 | Male | 69 | A 69-year-old Saudi man with diabetes mellitus was admitted to the Neurology Department with an unremitting headache lasting 5 days, episodic confusion, and visual disturbances. According to his family, the headache started gradually over the left side of his head and then became holocephalic and moderate to severe in intensity. The patient reported feelings of nausea and 2 episodes of vomiting. Moreover, his family stated the patient was often seen "bumping" into surrounding objects while ambulating. The patient reported experiencing some visual disturbance during this period. The patient's family felt he appeared confused at times and was not responding to his surroundings. He had no clear history of seizure, according to the family, and his past medical history was unremarkable apart from diabetes. He had sustained a minor head trauma 3 years prior with no concussion; however, his scan was reported to have shown "scattered areas of bleeding" in his brain. He otherwise maintained a healthy life and never required a hospital visit for any medical issues. His family reported the patient had normal cognitive function, especially as someone who ran his own business.
The patient was lethargic upon arrival to the accident and emergency department. Given the apparent risk of airway obstruction, the emergency physician intubated the patient. On general examination, we found no facial phakomas. While the patient was sedated, we found tonic eye deviation with nystagmoid-like eye movement and subtle myoclonic jerks of the distal limb suggestive of subclinical seizures. He was given an intravenous (IV) loading dose of phenytoin in addition to a midazolam infusion. Despite this, he sustained several clinical seizures in the subsequent days. Therefore, he required further titration of midazolam infusion (up to 14 mg/hr) and IV levetiracetam was added to optimize the antiepileptic coverage. His electroencephalogram was obtained postictal. His brain MRI was obtained 1 day following suspected subclinical seizures. Laboratory investigations showed peripehral blood cell count, haemoglobin, renal and liver function within reference range, and his blood glucose was elevated (14.7 mmol/L/264mg/dl).
Moreover, the results of his thyroid function test and his parathyroid hormone and serum vitamin B12 levels were normal. His serum folate level was not available. The screening tests for Hepatitis B antigen, Hepatitis C virus, and human immunodeficiency virus antigens and antibodies were all negative. His anti-TTG immunoglobulin A (IgA) titre was high at 35 U (reference range is up to 20 U), and the screen for antiendomysial antibody was negative, and his anti-Gliadin IgA antibody results were within reference range. Cerebrospinal fluid (CSF) study showed a WBC of 1, red blood cell count of 1, protein level of 36mg/dL, and a glucose level of 7.6mmol/L. The results of the CSF tuberculosis and herpes simplex virus 1 and 2 polymerase chain reaction were negative. We performed a duodenal endoscopic biopsy, but the specimen was not prepared properly; therefore, histopathological examination was suboptimal. We did note, however, increased intraepithelial lymphocytes with normal villous architecture.
The computed tomography (CT) of the patient's brain showed bilateral scattered corticosubcortical parietooccipitotemporal calcification with no oedema or mass effect (Figure 1). The brain MRI with and without contrast showed diffusion-weighted imaging (DWI) restriction over bilateral occipital cortex (more so over the left side) in a gyriform pattern (Figure 2) with concordant area of apparent diffusion coefficient (ADC) hypointensity (Figure 3). Susceptibility weighted magnetic resonance sequences (susceptibility weighted imaging [SWI], susceptibility weighted angiography [SWAN]) demonstrated hyperintensity corresponding to the area of DWI restriction (Figure 5). T1-weighted imaging with contrast showed no contrast uptake (Figure 4), and we saw no oedema or mass effect. We found no cortical atrophy or any deep cerebral vein enlargement. A second brain CT after 1 month (Figure 6) showed no interval change compared to the initial CT and no evidence of residual changes observed in MRI (DWI, ADC, and SWI).
Bilateral cortical calcification has a distinct set of mimickers, and Sturge-Weber syndrome (SWS) is first among the possible differentials. Our patient's brain CT may indeed look identical to SWS. However, it is the constellation of clinical and radiological features that differentiate the two conditions. The important clinically distinguishing feature of SWS is our patient's normal cognition. Psychomotor retardation is seen in 50% of SWS cases, and our patient lacked facial nevus which is prevalent in most SWS cases (except SWS Roach classification type 2). Our patient also had no ocular disease, a presentation found in 77% of SWS cases. Radiologically, SWS has tram line or gyriform-only cortical calcification (and not subcortical, as in our patient). Bilateral calcification (as seen in our patient) occurs in only 25% of SWS patients. Other radiological findings of SWS not seen in our patient are ipsilateral choroid plexus hypertrophy, enlarged transcortical (medullary) veins, ipsilateral cortical atrophy, enlargement of the ipsilateral ventricle, loss of volume of the ipsilateral cranial cavity, and pial enhancing angiomatous malformation (usually ipsilateral to the facial angioma). Therefore, many classic SWS features were not identified in our patient, distinguishing his condition from SWS.
Other conditions known to cause cortical calcification in a similar pattern are, namely, congenital folate malabsorption or the adverse effects associated with methotrexate and antifolate agents. There was no mention of the use of either of these agents. Congenital folate malabsorption would have an associated life-long history of symptoms of malabsorption which is not apparent in our patient. Cortical laminar necrosis could account for such radiological presentation. However, this entity is conventionally thought to be a sequela of a remote traumatic brain injury, anoxic-ischaemic injury, or a metabolic insult that is not present in this patient's past history. Moreover, characteristically, cortical laminar necrosis has T1-weighted gyriform hyperintensity in MRI which was not noted in this patient. Although each of these conditions gives rise to calcified shadows in brain imaging, none are anti-TTG IgA-positive which is specific for the diagnosis of CD.
Antiepileptic treatment with phenytoin and levetiracetam was commenced immediately upon the realisation that the patient has seizures. With the diagnosis of probable CEC, he was started on a strict gluten-free diet.
The patient recovered remarkably and regularly submits to follow-up examinations at our neurology clinic. At his last visit (9 months from his presentation), we found no residual neurological deficit other than mild homonymous hemianopia. Currently, he is fully active, self-sufficient, and has not sustained any seizure for the past 9 months. | null | Not supported with pagination yet | null |
PMC9512018_01 | Male | 68 | A 68-year-old man presented with generalized blisters in the scrotum for more than ten years. The patient developed several pale blisters, ranging from needle tip to grain size, with a smooth surface on the scrotum without obvious cause. He had no apparent symptoms and was diagnosed with "scrotal eczema" at a local hospital. Although he was given a glucocorticoid ointment (unspecified), the symptoms did not resolve. In the last three years, blisters increased significantly and spread over the entire scrotal surface without itching and pain. Some blisters fused into a bulla, and some blisters ruptured and exuded. Therefore, he came to our hospital for treatment. He had no history of chronic diseases such as hypertension, diabetes, coronary heart disease, and cerebral infarction and no history of infection such as tuberculosis and malaria. Similarly, he reported no history of drug or food allergies. The patient's parents, younger brother, and sister did not show similar skin lesions.
Physical examination revealed no superficial lymph node enlargement in the groin. The thickened skin and the deepened folds on both sides of the scrotum were observed. The scrotal surface was covered with numerous blisters without peculiar smell and tenderness. The blister wall was thick with a clear boundary. The blister was filled with colorless or reddish serous exudates. Some blisters fused into a bulla (Figure 1A and B). No similar lesions were observed in other parts of the body.
All laboratory results were normal. The acetowhite test was also negative. The abdominal CT and B-ultrasound showed no abnormalities. Histopathological examination of the skin revealed that the cystic spaces of dermal cells were mainly filled with light red serous fluid, and a few inflammatory cells were observed around the cystic spaces, which was consistent with the pathological diagnosis of lymphangioma (Figure 2A and B). Immunohistochemistry showed positive CD31 (Figure 2C and D) and D2-40 protein (Figure 2E and F). Therefore, the patient was diagnosed with a simple-acquired lymphangioma of the scrotum. Thus, the patient received a carbon dioxide laser (CO2 laser) to individually cauterize the blisters at the skin lesions and remove the blisters until normal tissue was visible. The patient was also instructed to apply potassium permanganate solution (1:8000) to the wounds apart from laser therapy once a day and fusidic acid ointment twice a day. The patient was followed up continuously, and during one year of the follow-up, no relapse, scars, or other complications occurred. | carbon dioxide laser, lymphangioma, scrotum | Not supported with pagination yet | null |
PMC4735082_01 | Female | 35 | An otherwise healthy 35-year-old woman presented to our clinic in Central Texas complaining of malaise, whole body rash, and joint pain of 2 days duration. She had recently returned from her honeymoon in Bora Bora after a ten day stay. She stayed in an air-conditioned resort but did sleep a few nights under a mosquito tent in the tropical forest where she suffered from multiple insect bites. On physical examination, she was afebrile. She had conjunctivitis and an erythematous maculopapular eruption on trunk and extremities as well as a lower extremity petechial eruption (Fig. 1).
Labs revealed a white blood count of 4400 cells/muL and normal platelet count. An arboviral illness was suspected and as French Polynesia is currently experiencing an outbreak of Zika fever, we contacted the CDC Arboviral division for specific ELISA Antibody testing. Our patient had positive IgM ELISA testing for both Zika and Dengue (as cross-reactivity of tests commonly occurs with Dengue and/or Chikungunya). Subsequent serum dilution-plaque reduction neutralization test was positive only for Zika virus. Convalescent sera 4 weeks later confirmed the diagnosis of Zika fever. Treatment, like other flavivirus illnesses, is supportive care only.
Zika virus was first described in Uganda in 1947 and subsequently in Senegal, Nigeria, and Micronesia. It is a zoonotic illness transmitted via Aedes spp. mosquitoes. Symptoms, as in our patient, are non-specific and include fever, malaise, arthralgias, synovitis, conjunctivitis and rash. It is a mild and self-limiting illness, typically lasting no more than 5 days. Zika fever must be kept in mind for any traveler that returns from an endemic region with a non-specific febrile illness and rash. | fever in a traveler, flavivirus, outbreak, zika fever | Not supported with pagination yet | null |
PMC5234200_01 | Male | 58 | A 58-year-old man presented with a complaint of headache of 2-month duration. There was no history of fever, vomiting, altered sensorium, or neurological deficit. The patient complained of breathlessness on exertion, but there were no symptoms of cough, chest pain, or hemoptysis. The patient was a smoker with a smoking history of 20 pack years. Auscultation of the chest revealed decreased breath sounds over the right upper lobe area. Laboratory investigations revealed anemia (hemoglobin, 9.2 g/dL) and hypoalbuminemia (albumin, 3.1 g/dL). Magnetic resonance imaging of the brain showed the presence of multiple space occupying lesions. CT of the thorax showed a large bulla in the right upper lobe and emphysema in both the lung fields. A spiculated nodule measuring 2.8 cm x 2.7 cm was seen in the right middle lobe, about 1.5 cm away from the hilum [Figure 1a and b].
Flexible bronchoscopy (BF-P180, Olympus, Japan; external diameter 4.9 mm, channel size 2.0 mm) was performed in the supine position under conscious sedation (midazolam and pentazocine) and topical anesthesia. Airway inspection revealed no abnormalities. The flexible bronchoscope was removed, and CP-EBUS bronchoscope (BF-UC-180F, external diameter 6.9 mm, Olympus, Japan) was inserted for sampling the lesion. However, the CP-EBUS scope could not be negotiated into the middle lobe. Subsequently, the radial EBUS probe (UM-S20-17S radial ultrasound probe, Olympus Japan; 1.4 mm distal end diameter, 20 MHz operating frequency) placed in a guide sheath (K-201, outer diameter 1.95 mm, Olympus, Japan) was used for localizing the nodule. The lesion was visualized adjacent to the lateral segment of the right middle lobe at the very proximal end of the segmental bronchus. The radial probe was removed, and TBNA was performed using a 21-G needle (Smooth Shot, NA-401D 1321; minimal channel size required 2 mm, Olympus, Japan) at the visually chosen site under endoscopic vision [Figure 1c]. The needle was moved to and fro 10-15 times within the mass. Three passes were obtained from the same site, and the aspirate was submitted for cytological examination. Brush cytology and TBLB were considered inappropriate due to the proximal location of the nodule.
Cytological examination revealed clusters of tumor cells with intracytoplasmic mucin suggestive of adenocarcinoma [Figure 1d]. The patient was administered dexamethasone and phenytoin in view of the brain metastases. He was planned for palliative radiotherapy and single agent chemotherapy in view of his poor performance status (Karnofsky Performance Score 60). However, the patient developed recurrent seizures and succumbed to his illness. | endobronchial ultrasound, guide sheath, lung cancer, transbronchial needle aspiration | Not supported with pagination yet | null |
PMC6758928_01 | Male | 0 | An 18 months old male child presented with an accidentally detected abdominal mass. Radiological examination with a triphasic computerized tomography (CT) scan showed multifocal masses in segments IVB, V, VI, and VIII of the liver with associated an extrahepatic extension. The serum alpha-fetoprotein (AFP) was 7,109 ng/ml [normal: 0-9 ng/ml]. The staging assigned was PRETEXT IIIE. An image-guided biopsy was suggestive of fetal epithelial type hepatoblastoma. The patient received six cycles of superPLADO chemotherapy i.e., cisplatin, doxorubicin, and carboplatin. A response evaluation after completion of chemotherapy revealed a fall in AFP levels to 4,049 ng/ml and a marginal decrease in size on CT scan (POSTEXT III). Extended right hepatectomy was planned, however, the estimated future liver remnant (FLR) was 26.8% of the liver volume. In view of the borderline FLR, a preoperative portal vein embolization (PVE) was considered to reduce the chance of postoperative liver failure. A 4F catheter was used for PVE with polyvinyl alcohol (PVA) particle of the right branch and one more cycle of chemotherapy was offered as a bridge to surgery. After 25 days the FLR enlarged to 50% of the liver volume with a volume gain of 104% and kinetic growth rate of 5.8% per week (Figure 1). An extended right hepatectomy was performed. The liver parenchyma was transected with a combination of Kelly clysis and harmonic scalpel. The right hepatic duct was secured further to the confluence of the bile duct and the integrity of the left duct was ensured. The postoperative recovery was uneventful and the child was discharged on the seventh postoperative day. The histopathology revealed residual mitotically active fetal type hepatoblastoma with minimal response to chemotherapy (99% viable tumor). The resection margins were more than 2 cm away and free of tumor cells. The child presented with fever, four weeks after the surgery. Ultrasonography (USG) revealed a cystic collection in the hepatorenal pouch for which a percutaneous drainage catheter was placed which drained bile. The biliary leak persisted with no regression in the daily drain output (>100 ml/day). A hepatobiliary iminodiacetic acid (HIDA) scan was undertaken to identify the site of the leak which revealed bile leak from the hilum. A percutaneous transhepatic biliary drainage (PTBD) was attempted for diversion of the bile from the hilum, however, it was unsuccessful. An endoscopic retrograde cholangiopancreatography (ERCP) and a plastic stent were placed in the left hepatic duct, however, the bile leak persisted (Figure 2). With the failure of conservative, endoscopic, and percutaneous procedures surgery was offered. On exploration, the stent was found protruding into the peritoneal cavity at the hepatic duct confluence (Figure 3). The hilar structures were meticulously dissected amidst the severe inflammation secondary to bile leak. The caliber of the hepatic duct was 1.5 mm and under magnification side to side Roux-en-Y hepaticojejunostomy with 7-0 polypropylene sutures was performed. Due to the fragile nature of tissues, a PTBD was attempted intraoperatively to reinforce the anastomosis. After successful cannulation of the biliary system, an interno-external stent was placed across the anastomosis (Figure 4). The bile leak stopped postoperatively and the child recovered well. The child completed the remaining three cycles of adjuvant chemotherapy and is disease free at 2 years after completion of treatment. | future liver remnant (flr), hepatic resection, hepatoblastoma, percutaneous transhepatic biliary drainage (ptbd), portal vein embolization, post-operative biliary leak | Not supported with pagination yet | null |
PMC5406809_01 | Female | 13 | A 13-year-old girl reported to the Department of Orthodontics and Dentofacial Orthopaedics, Army College of Dental Sciences, Secunderabad, with the chief complaint of forwardly placed upper front teeth and spacing [Figures 1a, 2a and 3a].
A full set of records needed for treatment planning were obtained which included:
Study models
Lateral cephalogram
Orthopantomogram (OPG)
Intraoral periapical (IOPA) X-rays of all the anterior teeth
Extraoral and intraoral photographs.
Analysis of the records showed the patient to be a skeletal Class II malocclusion with a deficient mandible which necessitated functional orthopedic therapy with the "Twin-Block appliance" to aid in mandibular advancement enabling correction of the sagittal skeletal discrepancy initially. The case would be reassessed for further dental treatment after completion of the functional phase. The functional appliance was a two-piece type with separate upper and lower components fabricated in heat-cured acrylic resin. Retention was obtained with stainless steel ball end clasps [Figure 4].
The patient reported with a diffuse swelling measuring approximately 40 mm in height and 53 mm in length on the left side of the face in the submandibular region after a period of 40 days [Figures 1b and 2b]. Case history revealed that the swelling developed over a period of 3 days with no signs of any respiratory tract infection or fever. On extraoral examination, a single, diffuse nonmovable swelling was observed in the left submandibular region which was nontender on palpation and firm in consistency. Intraoral examination showed no lesions, ulcerations or any tooth-related anomaly [Figure 3b]. Moreover, the oral hygiene status of the patient was also good. Bimanual palpation of the submandibular gland showed a normal gland texture. Salivary gland duct evaluation showed no abnormality with no history of "meal time syndrome." Salivary flow tests were done, and results were within normal limits. Lymph node examination of the body in general was carried out to rule out generalized lymphadenopathy. The only positive clinical finding was a slight reduction in mouth opening owing to the swelling present in the region. A provisional diagnosis of reactive lymphadenopathy was made.
The functional therapy was immediately discontinued. Diagnostic IOPAs of the developing second molar regions as well as an OPG were recorded [Figure 5]. The patient was advised investigations including a complete blood picture, ultrasonographic (USG) evaluation of the left submandibular gland region [Figure 6] and a FNAC. The blood reports were nonspecific with the only significant finding being a mildly elevated erythrocyte sedimentation rate. USG scan revealed that the left submandibular gland was slightly enlarged as compared to the right with altered echotexture and increased vascularity on color Doppler. Enlarged cervical lymph nodes were noted at Levels I mainly and few in Level II and III during USG examination, with the largest one measuring 2.3 cm x 1.0 cm. Acid-fast bacillus smear and Mantoux test were done to rule out tuberculosis, and the test results were negative. Microscopic evaluation of the FNAC from left submandibular gland revealed few cells. It contained mostly blood and occasional salivary gland acini which were inadequate for diagnosis.
A final diagnosis of reactive lymphadenopathy with submandibular gland sialadenitis was given. After discussion with an oral surgeon, a period of observation without using any medication and temporary discontinuation of the appliance was decided on. The patient reported to the clinic 3 days later without any swelling which was surprising considering its size on initial presentation. As a matter of precaution, orthodontic appliance therapy was temporarily halted for another 3 weeks. The patient started wearing the removable functional appliance after completion of the period of observation. Treatment progressed smoothly with no further recurrence in symptoms. | delayed hypersensitivity, lymphadenopathy, orthodontic therapy, salivary gland enlargement | Not supported with pagination yet | null |
PMC3745288_01 | Female | 56 | A 56-year-old female patient presented after a fall, with worsening lower extremity edema. She was found to have acute-on-chronic kidney injury (7.46 mg/dL on baseline creatinine of 2.42 mg/dL). Past medical history was significant for diabetes mellitus type II and diabetic neuropathy, morbid obesity (body mass index = 48 kg/m2), deep venous thrombosis, and pulmonary embolism, receiving warfarin for 2 years and 9 months, dyslipidemia, hypertension, chronic kidney disease stage I V, and peripheral vascular disease status post-amputation of the left toe 5 months earlier. Workup for acute kidney injury (AKI) was conducted, excluding post obstructive, prerenal, vasculitis, and multiple myeloma. The patient had a drop in hemoglobin; warfarin was withheld for 4 days on suspicion of blood loss and then restarted on day 6 (international normalized ratio [INR] = 1.6 reaching 1.3) after placement of an Ash catheter and initiation of dialysis with INR target in the range of 2-3, which was maintained throughout the entire hospital stay.
The patient developed a right foot blister on day 7 and bilateral thigh blisters on day 10 (Figure 4) that were attributed initially to volume overload. Laboratory values were as follows: serum calcium (Ca) 7.4 mg/dL, albumin 2.9 g/dL, inorganic phosphorus 10.3 mg/dL, creatinine 7.68 mg/dL, blood urea nitrogen (BUN) 98 mg/dL, erythrocyte sedimentation rate (ESR) 122 mm/hr, intact parathyroid hormone (PTH) 368 pg/mL, glucose 109 mg/dL. The patient had significant proteinuria of 8,456 mg/g, attributed to diabetic nephropathy (glycated hemoglobin [HbA1c] 5.2%). Total bilirubin was 0.5 mg/dL, alkaline phosphatase was 65 IU/L, aspartate aminotransferase (AST) was 15 IU/L, and alanine aminotransferase (ALT) was 24 IU/L.
The skin became mottled and the lesions worsened progressively over 3 days to become necrotic eschars (Figure 5). Similar lesions developed over the lower extremities, flanks, and lower abdomen (Figure 6). Extended workup for vasculitis, autoimmune disorders, and coagulopathies was conducted and all were negative: anti-nuclear antibodies (ANA), anti-smith antibodies, anti-double-stranded DNA (dsDNA), anti-ribonucleoprotein (RNP) antibody, anti-neutrophil cytoplasmic antibodies (ANCA) (proteinase-3 AB and myeloperoxidase AB), Sjogren A and Sjogren B antibodies, C3 and C4 complement level, immunoglobulin (Ig)G anti-platelet factor (PF)-4, lupus anticoagulant, anti-cardiolipin IgG and IgM, anti-phospholipid IgM IgG antibodies, beta2 glycoprotein I IgG IgM IgA antibodies, hepatitis serologies for hepatitis C and B virus, and workup for multiple myeloma. Protein C function was 33%, expected secondary to Coumadin therapy. Protein S activity, antithrombin III, IgA-IgM-IgG levels were all normal.
The patient became septic, with persistent leukocytosis and low-grade fever, along with worsening of skin lesions (Figure 7), with white blood count of 26 TH/mm3, platelet count of 264 TH/mm3, albumin of 1 g/dL, AST of 38 IU/L, ALT of 37 IU/L, total bilirubin (Tbil) of 0.5 mg/dL, and alkaline phosphatase of 124 IU/L.
The patient had eschar lesions on the right lower extremity (75 x 20 cm), the left lower extremity (75 x 20 cm), and an abdominal lesion (10 x 5 x 5 cm) (Figure 8). The burn specialist provided care and the patient underwent skin debridement and wound care; however, all resuscitation efforts failed on day 42.
A skin biopsy was performed and showed a portion of skin and subcutaneous tissue with diffuse necrosis and focal acute inflammation as well as multiple small arteries showing calcification of the tunica media. This pattern is strongly suggestive of calciphylaxis (Figure 1). Autopsy confirmed our diagnosis, with diffuse calcification of the splanchnic and renal arteries media.
WISN usually appears 3-10 days after starting warfarin, but can occur after many months to 15 years. WISN and calciphylaxis shares similar clinical findings and only biopsy of the skin can differentiate between the two conditions, showing a thrombotic occlusion in dermal, subcutaneous vasculature with hemorrhage. WISN lesions predominate in areas where there is relatively greater adipose tissue, for example, the breasts, thighs, hips, and buttock region.
All workup for AKI and skin necrosis was conducted and vasculitis, multiple myeloma, coagulation disorder, heparin-induced thrombocytopenia, and cryoglobulinemia were excluded. The skin biopsy confirmed our diagnosis and excluded disseminated intravascular coagulation and other microthrombotic etiologies.
The pathogenesis of calciphylaxis is not well-known. It is related to many conditions such as malignancies, cirrhosis, primary hyperparathyroidism, and secondary hyperparathyroidism as a result of short-bowel syndrome and Crohn's disease. Previous observational studies have suggested several risk factors, including hyperphosphatemia, hypercalcemia, low serum albumin levels, female gender, obesity, diabetes mellitus, calcium content of the skin, warfarin therapy, systemic corticosteroid use, and elevation in alkaline phosphatase. Clarifying the causality relationship of many coexistent conditions in end-stage renal disease is challenging.
Hayashi et al conducted a multivariate analysis and found that there was a 10.1-fold higher risk of calciphylaxis with warfarin therapy.
Cases of calciphylaxis have been reported as occurring in the absence of hyperparathyroidism and renal failure. These findings support the view of calciphylaxis as a final common endpoint of an independent pathway. Calciphylaxis is believed to occur as a product of culminating conditions and stimuli via a final common pathway involving the nuclear factor kappa-beta activation, leading to vascular calcification.
Descriptive cross-sectional data in humans as well as experimental data in rodents report a positive correlation of vitamin K antagonists and vascular calcification, leading to wide concern regarding the use of warfarin in cardiovasculopathic patients, and the viewing of this disease as partly iatrogenic when it is not a well-known natural sequel of chronic kidney disease (such as renal bone disease or renal hypertension or renal anemia).
Warfarin therapy provokes an unbalanced pro- and anti-calcification factors, by inhibiting a matrix G1A protein responsible for inhibiting the mineralization of tissues. Matrix G1A protein is an 84 amino acid vitamin K dependent that is activated by carboxylation of glutamate residues. In rat models, the disruption of this protein led to extensive vascular calcification, and this possibly occurs in patients receiving long-term warfarin therapy. Retrospectively, vitamin K supplementation can lead to suppression of the calcification tendency.
There are two subtypes of vitamin K: vitamin K1 is the most important for the activation of hepatic clotting factors, and vitamin K2 is involved in the inhibition of calcium deposition in the vasculature. Genetic variation and differential gamma-carboxylation at the glutamate residues is thought to be responsible for the varying phenotypes and susceptibility to vascular calcification.
As this is a multifactorial disease, multifactorial treatment may be a successful intervention tool.
Supportive treatment includes wound and pain management. Some success has been achieved with hyperbaric oxygen and intravenous sodium thiosulfate therapy. Correction of hypercalcemia and hyperphosphatemia is essential for treatment. Parathyroidectomy may benefit patients with refractory hyperphosphatemia.
We hypothesize that the reintroduction of warfarin creates an imbalance favoring calcification in the vessels in previously sensitized conditions, which set our patient up for a catastrophic acceleration of vascular calcification.
Understanding the pathophysiology of this process will certainly enhance our treatment approach and reduce the morbidity and mortality of this devastating condition. | esrd, calciphylaxis, skin necrosis, warfarin | Not supported with pagination yet | null |
PMC8097161_01 | Male | 25 | A 25-year-old man with no medical history living in Paris, France, went to the local emergency room in November 2018 with sudden onset of psychotic symptoms (paranoid delusions, auditory hallucinations and major anxiety) associated with fever, cough and general asthenia. He had no psychiatric history apart from an anxious personality and a mild tobacco and cannabis consumption and was not taking any medication. He had travelled in Greece for one week and had returned ten days before the first symptoms. He reported having unprotected sex with a man 2 months before and during his travel.
On admission, he had fever (38.5 C), pharyngitis, oral candidiasis and skin rash. Laboratory values revealed increased C-reactive protein (18 mg/L), mild anemia (10.5 g/dL) with low reticulocytes count (37 G/L), lymphopenia (500/mm3), neutropenia down to 600/mm3 and thrombocytopenia (90 G/L). HIV-1 serology returned positive, confirmed by immunoblot, with a viral load of 5.47 million copies/mL and a CD4+ T-cells count of 90/mm3. Neuroleptic drugs (cyamemazine, risperidone) and benzodiazepines were introduced to treat psychotic and anxious symptoms. He was transferred to our Infectious Diseases Department. HIV blood viral load at admission (2 weeks after first symptoms) was at 6.85 million copies/mL with a blood CD4+ T-cells count of 30/mm3 and a global lymphopenia (including CD8+ and NK cells). The immunoblot showed an uncommon band pattern (gp120 and gp41 reactivity, weak ambiguous reactivity to p24 and p31, no reactivity to other antigens), which could have been consistent with acute primary infection. He never had any HIV infection screening in the past. The research of past blood tests showed a normal lymphocytes count (1.4 G/L) a year ago. Of note, his recent partner was just diagnosed with HIV infection as well.
Lumbar puncture, electroencephalography and cerebral MRI showed no abnormality. Thoraco-abdominal and pelvic CT revealed homogenous hepatosplenomegaly and few parenchymatous interstitial pulmonary lesions (micronodules and reticulations). Sputum cultures and bronchoalveolar lavage showed no Pneumocystis nor tuberculosis infection. No co-infection with HAV, HBV, HCV, HEV, toxoplasmosis nor syphilis was found. EBV and CMV viral loads were undetectable. Genotypic testing found a CRF19-cpx strain. Combined anti-retroviral therapy (cART) was introduced 2 weeks after diagnosis, consisting in tenofovir, emtricitabine and raltegravir, and Pneumocystis pneumonia was prevented by cotrimoxazole.
Despite cART and neuroleptic drugs, psychotic symptoms and fever persisted associated with chills, sweats and a neurological disorder occurred with bilateral muscle rigidity. The worsening of his clinical state required intensive care. A neuroleptic malignant syndrome was diagnosed, and extrapyramidal syndrome recovered after stopping neuroleptic treatment, but fever, chills and night sweats persisted. At this time, blood tests showed worsening pancytopenia (anemia 7.0 g/dL, platelets count 50 G/L, neutropenia 600/mm3), hyperferritinemia, elevated liver enzymes and mild elevated triglyceridemia. We hypothesized that the patient had a hemophagocytic lymphohistiocytosis (HLH) triggered by an acute primary HIV infection. Sternal bone marrow aspiration was performed showing signs of macrophages activation without hemophagocytosis. No Leishmania was found on bone marrow aspirate smears and Mycobacterium tuberculosis complex PCR was negative. An empiric treatment with intravenous immunoglobulins 1 g/kg for 2 days was administered; no clinical response was observed.
Finally, a bone marrow biopsy was performed showing hemophagocytosis, confirming HLH, and moreover, revealing the presence of Leishmania spp ( Figure 1 ), with a low parasitic load. Serology was also positive for Leishmania infantum antibodies by immune-enzymatic screening technique, confirmed by Western-Blot assay. Molecular species identification confirmed a Leishmania infantum strand.
Intravenous liposomal amphotericin B was administered at 4 mg/kg/day on five consecutive days followed by five weekly administrations, allowing complete clinical recovery and pancytopenia recovery. Patient was discharged, no secondary prophylaxis against VL was prescribed. Viral load decreased to 75 copies/mL and CD4+ T-cells count increased to 213/mm3 two months after cART initiation and viral load was undetectable with CD4+ T-cells count at 345/mm3 after 6 months ( Figure 2 ), with no sign of VL relapse. After 24 months of follow-up, no VL relapse was observed. | hiv, bone marrow aspirate, hemophagocytic lymphohistiocytosis, pancytopenia, visceral leishmaniasis | Not supported with pagination yet | null |
PMC4833829_02 | Male | 57 | A 57 year old Portuguese man, with no past medical history, presented on December 7 2015 complaining of chills, generalized asthenia and myalgia and rash, one day after returning from Rio de Janeiro after a 10 day stay. The study in the hospital revealed thrombocytopenia (126 000/muL), without leukopenia or abnormal liver enzymology. Real-time PCR was positive for Zika virus in the urine sample.
The patient received supportive treatment, improving clinically to symptoms free.
Previous flavivirus infections and vaccination against flaviviruses (yellow fever, tick-borne encephalitis and Japanese encephalitis viruses) were not reported by any of the patients. The data of these four imported cases to Portugal is summarized in Table 1.
In the National Institute of Health, sera samples were tested by immunofluorescent assay (IFA) in-house (IgG and IgM) for Zika virus (ZIKV), Dengue (DENV) and Chikungunya viruses (CHIKV) (Table 1). The presence of immunoglobulins specific to other flaviviruses, such as yellow fever (YFV), tick-borne encephalitis (TBEV) and West Nile (WNV) viruses was also tested by IFA and all assay results were negative for IgM and presented cross-reaction signals in IgG.
Nucleic acids were extracted from 400 muL of ethylenediaminetetraacetic acid (EDTA) blood samples and 900 muL urine samples using NucliSens easyMAG platform (BioMerieux). The presence of ZIKV RNA was checked by real-time RT-PCR and conventional reverse transcription-polymerase chain reaction (RT-PCR) using Zika specific primers and pan-flavivirus primers targeting the non-structural protein 5 (NS5) gene. The presence of DENV and CHIKV RNA was checked by real-time PCR as reported previously, and by conventional RT-PCR, respectively. For cases 1 and 2, Zika RT-PCR was negative (conventional and real time RT-PCR) on blood samples collected on day 13 post onset of disease. For cases 3 and 4, real time RT-PCR and conventional RT-PCR were positive in urine samples on day 8 and 9 post onset, respectively. The nested- PCR fragments (overlapping NS5, 205 bp) was sequenced bi-directionally and submitted to GenBank (accession numbers KU752544 and KU752545). Similarity searches were made within the GenBank data set using the basic local alignment search tool (BLAST) BLASTN algorithm. Maximum likelihood analysis was performed with Kimura two-parameter model with invariant sites using Mega version 6 software. The robustness of the nodes was tested by 1000 bootstrap replications. | arbovirus, imported cases, zika virus | Not supported with pagination yet | null |
PMC8276930_01 | Female | 56 | In June 2019, a 56-year-old woman without a relevant medical history underwent right renal tumourectomy. Histology findings demonstrated clear cell renal cell carcinoma (RCC), sarcomatoid type, grade 4 (Fuhrman), free margins, pT1b Nx M0. On 26 July after a multidisciplinary team discussion (MTD), follow-up with chest and abdominal CT scans within 1 month was scheduled.
In August 2019, the patient was admitted to the emergency department for neurological symptoms. A brain CT scan showed a left frontal lesion. She was admitted to the neurology department and started steroid treatment. A whole-body CT scan confirmed progressive disease with mediastinal node involvement and two enlarged abdominal nodes (one perirenal and one close to the right iliac vessels).
Steroid therapy during hospitalization resulted in improvement.
In August 2019, the MTD advised radical single brain metastasis excision followed by systemic therapy. The patient underwent brain surgery. Histology showed epithelial neoplasia with clear cell aspects and large necrotic areas, immuno-morphologically consistent with secondary RCC.
In October 2019, the patient started combination immunotherapy with ipilimumab and nivolumab. After 1 week, liver toxicity was reported (grade 2 on aspartate aminotransferase (AST) and alanine transaminase (ALT), and grade 3 on total bilirubin (TB) and direct bilirubin (DB)). The patient then underwent a liver ultrasound (Fig. 1) which was negative for metastasis. She was started on oral prednisone 25 mg (1 capsule) three times a day.
On 4 November, due to progressive liver impairment, the patient started methylprednisolone at 2 mg/kg. Alternative causes for the liver impairment were investigated and excluded. Tests for hepatitis A, B and C infection, cytomegalovirus and immune hepatitis were performed and resulted negative.
Budd-Chiari syndrome was excluded because neither imaging or coagulation status were suggestive for the disease.
Blood analysis demonstrated worsening liver toxicity. We considered the liver failure was due to immune-related toxicity and increased the steroid dose. The patient was admitted to the oncology ward to start intravenous high-dose steroids according to international guideline . The patient's medication included 2 mg/kg methylprednisolone (daily dose 80 mgx2), euthyrox 125 mug, levetiracetam 500 mgx2, furosemide 20 mg x 2, omeprazole 20 mg x2 in the evening, delorazepam 8 mg in the evening, and cetirizine 10 mg (1 capsule)x2. The blood results during treatment are given in Table 1.
In November 2019, the patient underwent an abdominal CT scan (Fig. 2A) which showed a slightly enlarged liver without focal lesions. Liver enzymes continued to increase without impairment in coagulation function. The patient maintained a fair general condition until the beginning of December 2019.
At the end of November, the patient started mycophenolate 100 mg twice daily and underwent liver ultrasound plus-guided biopsy (Fig. 3). Liver enzyme trends are shown in Fig. 4. The histology report noted hepatic tissue with cytoplasmic and intracanalicular cholestasis, sinusoid ectasia and histiocytosis, tissue macrophage or dendritic cell aggregation, and microfoci of liver necrosis in single or a few cells.
There was no evidence of endotheliosis.
On 11 December, the patient started the third-line immunosuppressive therapy with tacrolimus 2 mg daily. On 17 December, she underwent an abdominal CT scan (Fig. 2B) which showed progressive disease but no liver involvement. The patient's condition deteriorated and she died on 27 December. Her relatives did not consent to an autopsy. | hepatitis, hepatic failure, immunotherapy, renal carcinoma | Not supported with pagination yet | null |
PMC5977007_01 | Male | 23 | The patient was a 23-year-old male of Turkish/Kurdish descent of consanguineous parents (second-cousins) who had 4 healthy siblings and one sister with a rare lung disease not immediately associated with the patient's condition. His parents had lost a child at a few months of age with no certain diagnosis.
The patient had skin lesions from 2 years of age, affecting his face and extremities and to a lesser degree his truncus. The lesions appeared as purple plaques of the skin with variable thickness evolving into deep atrophic scars over time. There had been numerous biopsies over the years showing an uncharacteristic massive lymphoid infiltration dominated by CD8+ lymphocytes and histiocytes and with some granulomas (Figure 1). In lack of a more precise histopathological diagnosis and considering the clinical presentation, a diagnosis of sarcoidosis was given. Despite aggressive immunosuppressive therapy including corticosteroids, methotrexate, azathioprine, and anti-TNF agents, the lesions gradually evolved although in a slow and undulating manner. In a reevaluation of the skin biopsies, the pathologists found a diffuse lymphohistiocytic infiltrate dominated by CD8+ T-cells with several different monoclonalities as well as epithelioid cell granulomas. They concluded with a T-cell dominated lymphoproliferative state associated with a form of primary immunodeficiency, for example, a RAG-mutation. Meanwhile the patient underwent carmustine therapy on the suspicion of mycosis fungoides without any apparent clinical effect. One year before presentation at Oslo University Hospital, the patient was found to have a diffuse large cell B-cell lymphoma (non-GC-B type, EBV+) in a tumor of the neck and at the same time another different B-cell lymphoma (unclassifiable, with features intermediate between diffuse large-B cell lymphoma (DLBCL) and classical Hodgkin lymphoma) preauricularly (Figure 2). PET-CT showed a possible lymphoma in the right lung, and as such he was staged as IVA, aaIPI 1. He underwent chemotherapy (R-CHOEP 14x 6 + 2R) and radiation therapy against residual disease and went in complete remission with a negative PET-CT. His skin lesions, however, got worse throughout the chemotherapy and radiation therapy and continued to evolve with infiltration into the masseter muscle in the face and a similar histopathological picture was found in lesions diffusely infiltrating the liver and possibly spleen. The patient had no history of recurrent infections, autoimmunity, or other manifestations of a primary immunodeficiency beside his skin lesions and lymphoma.
At presentation at Oslo University Hospital, he was immunologically characterized by a slight hypogammaglobulinemia (IgG 6,1 g/L) and absence of B-cells in peripheral blood considered to be secondary to rituximab treatment (Table 1). However, low numbers but not absence of B-cells in previous bone marrow biopsies had been noted. He did not receive any immunoglobulin therapy. He was slightly lymphopenic (0,8 x 109/L) and had low levels of CD4+ cells (177 x 106/L) with an inversed CD4/CD8 ratio of 0,63. There was an absence of naive CD4+ T-cells and recent thymic emigrants. His CD8+ cell pool was expanded but had a normal phenotype. He had normal levels of double-negative T-cells and gamma-delta T-cells. Overall the T-cells seemed to be strongly activated with half being HLA-DR+. We have no data on proliferative response to mitogens or specific antigens.
There was a strong clinical suspicion of an underlying immunodeficiency but DNA-sequencing covering exons and introns to the RAG1/RAG2 gene did not reveal any mutations. Samples were taken for whole-exome sequencing, but while waiting for the results, the patient had a DLCBL-like relapse in the gastroventricular mucosa engaging pancreas and spleen with infiltration of irregularly shaped histiocytic cells and T-cells monoclonal for the TCR-gamma chain. Dose-reduced chemotherapy was initiated (isophosphamide, methotrexate, and etoposide), but after 3 days of therapy, a near catastrophic gastrointestinal bleeding occurred from the tumor. He went through extensive surgery and we received report of a homozygous missense mutation in exon 8 of the Artemis-coding gene DCLRE1C (NM_001033855.2: c.632G>T, p.G211V), while he was still in the intensive care unit. Sanger sequencing confirmed homozygosity in patient DNA and heterozygosity in his father and one of his siblings, while his mother was not tested. Fibroblastic culture furthermore revealed radiosensitivity consistent with an Artemis defect. The genetic variant has previously been reported as disease-causing in a patient from a patient cohort with radiosensitive SCID and Omenn syndrome. It has not been observed in databases for normal variation (ExAC and gnomAD).
The affected amino acid is located in the beta-CASP domain of DCLRE1C. Predicted secondary structure suggests that the amino acid is located in a six-amino-acid-sized stretch between a helix and a strand. The amino acid is highly conserved both between species and in members of the beta-CASP domain.
The patient was again evaluated by PET-CT and considered in complete remission after surgery and referred for HSCT. He had no severe comorbidity, and the now increasingly aggressive nature of his immunodeficiency made the case for HSCT well founded. None of his siblings were HLA identical and no matched unrelated donor could be identified. For practical reasons, availability as well as identical ABO type, we decided to choose his haploidentical father as the preferred haploidentical stem cell donor. The parents' heterozygosity for the Artemis mutation was considered irrelevant due to the recessive nature of the trait and their apparently normal immune function. Artemis mutated immunodeficiencies in general are likely to tolerate myeloablative conditioning, which gives the best long-term immune reconstitution with thymopoiesis and B-cell function. The options of (A) conditioning with alemtuzumab, treosulfan, fludarabine, and thiotepa using a TCR-alpha and -beta depleted graft versus (B) using a T-cell replete marrow graft after cyclophosphamide 14, 5 mg/kg days -6 and -5, flu 30 mg/m2 days -6 to -2 (5 days), and 200 cGy TBI day -1 with the addition of busulfan 3.2 mg/kg/day, days -4 and -3 to achieve myeloablation as conditioning and posttransplant cyclophosphamide 50 mg/kg days +3 and +4 and tacrolimus and mycophenolate mofetil as graft-versus-host-disease (GVHD) prophylaxis were discussed. We chose the latter option for our patient, and he received BMSC, only 1,7 x 108 NC/Kg, and stable engraftment was achieved at day +18. Donor chimerism was >99% at day 100. The posttransplant course was uncomplicated except for two episodes of CMV reactivation that was preemptively treated.
On Day 150, however, the patient was referred to hospital with fever and lung symptoms with CT scans demonstrating extensive lung infiltrates. Bronchoscopy with bronchoalveolar lavage was performed showing a positive PCR reaction for Pneumocystis jirovecii, and while the immunofluorescence test was negative, a Pneumocystis jirovecii pneumonia (PCP) was highly suspected. PCP prophylaxis with trimethoprim-sulfamethoxazole had been prescribed but the patient had for unknown reasons only taken this on and off. Further tests showed a positive Herpes simplex virus PCR reaction in plasma, and Staphylococcus aureus and Candida albicans were found in blood cultures. The patient was extensively treated with antibiotics including high-dose trimethoprim-sulfamethoxazole as well as corticosteroids and acyclovir. Sadly, however, he did not respond to this treatment and died on day 167. Autopsy was unfortunately not done. | null | Not supported with pagination yet | null |
PMC4247310_01 | Male | 67 | A 67-year-old male was admitted to the Surgical Outpatients Department of The First Affiliated Hospital of Soochow University (Suzhou, China), with a mass lesion (2x2 cm) on the right lung (Fig. 1). The lesion was detected during a routine medical examination. A video-assisted thoracoscopic lobectomy was performed to remove the mass, and histopathological examination revealed a lung adenocarcinoma with visceral pleural invasion. The patient underwent four courses of adjuvant chemotherapy (75 mg/m2 cisplatin and 100 mg/m2 gemcitabine) and was clinically diagnosed as disease free. However, the appearance of multiple patchy shadows on the right lung was observed in CT scans at 32 months following the surgery. The patient did not present any evident changes in the chest radiographs and serum tumor marker tests during the subsequent nine-month follow-up period. After the nine-month period, chest CT scans revealed a subpleural nodule (0.5x0.5 cm) and a slight enlargement of the patchy shadow on the right lung (Fig. 2). PET-CT scans revealed that the FDG uptake of the nodule had a SUVmax of 6.1. A that indicated malignant disease. A video-assisted thoracoscopic biopsy indicated that the patient suffered from tuberculosis (Fig. 3). Written informed consent was obtained from the patient. | lung cancer, positron emission tomography-computed tomography, recurrence, tuberculosis | Not supported with pagination yet | null |
PMC7369350_01 | Male | 25 | A 25-year-old male presented with blood stained expectoration of about 300 ml/day since 2 days and chest pain since one week with no similar complaints in past. He had history of shortness of breath and wheeze during childhood with no significant past and family history. On examination patient had tachypnea & tachycardia and saturation (SPO2) of 96% on room air. On auscultation left upper lobe crackles were heard. Laboratory findings were Haemoglobin 13.6 gm/dl, total leucocyte count of 15.500 cells mm3, ESR 44 mm/hr, Serum IgE 800IU/ml, sputum AFB stain and gene expert were negative. Liver function test, urine routine, renal function tests were within normal limits. Chest radiograph PA view (Fig. 1) revealed non homogenous opacity left upper and mid-zone. CECT chest (Fig. 2A and B) was suggestive of heterogeneously enhancing lesion measuring 6.4 x 6.8 x 5.6cm with internal areas of necrosis and surrounding ground glass attenuation in apico-posterior segment of left upper lobe with narrowing and partial occlusion of left apicoposterior segmental bronchus with few enlarged intrapulmonary lymphnodes. Videobroncoscope showed soft tissue endoluminal lesion completely occluding left upper lobe segments which bleeds on biopsy (Fig. 3). Bronchoscopic lavage, brushings and biopsy were done from left upper lobe lesion. Subsequently CT guided percutaneous biopsy was also performed from left upper lobe lesion.
Pending the reports patient was discharged. He got re-admitted after 5 days with persistent haemoptysis of about 100-200 ml, worsening of breathlessness and hypoxia with saturation of 88% on room air. His chest radiograph showed significant worsening of left upper lobe lesion. Patient was started on oxygen through nasal canula @ 2 L per minute, haemostatic agents & parenteral antibiotics.
Bronchial lavage was negative for AFB stain by Ziehl-Neelsen stain and on Gene Xpert, Mycobacterium TB was not detected. Bronchial lavage was also negative for malignant cells on cytological analysis with no growth on aerobic culture. On histopathology (Fig. 4A and B) endobronchial biopsy was suggestive of capillaritis with leucocytoclasis and infiltration by both acute and chronic inflammatory cells and occasional multinucleated giant cells. Histopathology of both bronchoscopic and CT guided biopsy showed granulomatous inflammation with multinucleated giant cells and microscopic haemorrhage suggestive of vasculitis. Further laboratory findings revealed a strongly positive value by enzyme-linked immunosorbent for antibodies anti PR3 autoantibodies (9.9IU/ml) and negative for MPO (<0.2IU/Ml).
A diagnosis of Granulomatosis with polyangiitis was made on basis of clinico-histopathological and serological evidence. Our patient was classified as having limited disease on basis of fulfilment of modified American College of Rheumatology criteria for the classification of GPA. Following the diagnosis, patient was started on intravenous methylprednisolone 1000mg in 250ml NS over 2 hours 3 days. Rituximab was given intravenously as four doses of 375 mg/m2 at weekly intervals (plus prednisolone 100mg on the day of infusion). Chest x-ray (Fig. 5) after one week of therapy showed significant clearance of left upper zone lesion along with clinical improvement with amelioration of breathlessness and haemoptysis. | endobronchial lesion, granulomatosis with polyangiitis, hemoptysis, wegener's | Chest CT showed heterogeneously enhancing lesion measuring 6.4 x 6.8 x 5.6cm with internal areas of necrosis and surrounding ground glass attenuation in apico-posterior segment of left upper lobe with partial occlusion of left apicoposterior segmental bronchus. |
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PMC5960554_01 | Female | 37 | A 37-year-old woman with chronic portal vein thrombosis and cavernous transformation presented due to a recurrent episode of hematemesis. She had previously undergone multiple esophageal band ligations for esophageal varices seen on esophagogastroduodenoscopy (EGD). Ultrasonography showed elevated portal pressures and magnetic resonance cholangiopancreatography (MRCP) showed portal vein thrombosis. In addition, there were dilated periportal varices (cavernous transformation) exerting mass effect on the extrahepatic common bile duct and severe intrahepatic biliary ductal dilation involving all hepatic segments. Liver enzymes were persistently elevated in a cholestatic pattern: aspartate aminotransferase (AST) 64 U/L, alanine aminotransferase (ALT) 48 U/L, alkaline phosphatase (ALK) 303 U/L, total bilirubin (Tbili) 8.4 mg/dl, albumin 3.8 g/dl, and prothrombin time 11.9 seconds.
The liver was noncirrhotic on biopsy. Computed tomography (CT) of the abdomen showed large varices in the porta hepatis and portal vein thrombosis that appeared chronic in nature with cavernous transformation. Operative management with a mesocaval shunt was planned with the hopes of reducing portal pressure and preventing recurrent GI bleeding, portal biliopathy, and secondary cirrhosis. A selective shunt, such as a splenorenal shunt, selects nonintestinal flow to be shunted to the systemic venous drainage and has the advantage of reducing the incidence of encephalopathy. This type of shunt, however, would not have adequately reduced variceal pressures and therefore the decision was made to proceed with a mesocaval shunt.
The patient underwent an ERCP to better assess the biliary anatomy, as part of the preoperative evaluation for a shunt. During the procedure, she developed active hemobilia (Figure 1) from a newly discovered periampullary varix (Figure 2). A biliary covered metal stent was immediately placed, but without hemostasis. Due to ongoing bleeding that required activation of a massive transfusion protocol, an exploratory laparotomy was performed with emergent mesocaval shunt placement (Figures 3 and 4). An 8 mm ringed polytetrafluoroethylene (PTFE) graft was used to create a mesocaval shunt between the proximal superior mesenteric vein (SMV) and the infrarenal inferior vena cava (IVC). Portal pressures decreased by 8 mmHg after shunting and the bleeding stopped. She remained hemodynamically stable and was discharged ten days postoperatively. Follow-up mesocaval shuntogram showed a patent shunt with an outflow pressure of 13 mm Hg at the IVC and a portosystemic pressure gradient of 12 mm Hg. Two months postoperatively, she had an AST of 56 U/L, ALT 51 U/L, ALK 416 U/L, and Tbili 0.9 mg/dl. To date, she has had no episodes of hepatic encephalopathy. | null | Not supported with pagination yet | null |
PMC9114644_01 | Female | 28 | A 28-year-old woman was admitted to the Second Xiangya Hospital of Central South University, Hunan, China because of recurrent cough for 6 years and wheezing for 7 months, which aggravated for half a month in May 2021. The patient started to cough sputum early in September 2014, and pulmonary tuberculosis was considered the reason at the local hospital and therefore anti-tuberculosis was given. The symptoms improved significantly until 2015; the patient complained of cough with fever during the anti-tuberculosis therapy and visited our hospital for the first time. Laboratory tests showed an elevated level of leukocyte count, erythrocyte sedimentation rate, C-reactive protein level, and serum total IgE (2,500 IU/ml, normal range: <130 IU/ml). The chest CT revealed multiple cavitary lesions in both upper lungs and the dorsal segment of the left lower lung and bronchiectasis of bilateral lobes (Figure 1A). A combined infection of aspergillosis and Staphylococcus aureus was confirmed by positive culture of both sputum and bronchoalveolar lavage fluid (BALF). Anti-infection with teicoplanin and itraconazole was prescribed, and her symptoms were relieved on therapy. The patient remained stable until 2019; she began coughing intermittently and the symptoms gradually worsened when accompanied with dyspnea and wheezing. She visited our hospital for the second time in December 2020. Blood tests showed a moderately elevated level of eosinophil count (0.97 x 109/L, normal range: 0.02-0.52 x 109/L) and a markedly increased serum total IgE level (>2,500 IU/ml). Total levels of aspergillosis-specific IgE, IgM, and IgG were above normal. A pulmonary function test revealed decreased FVC (2.41 L; expected value: 2.92 L), decreased FEV1 (1.54 L, expected value: 2.53 L), and decreased FEV1/FVC (63.68%, expected value: 84.52%), indicating moderate obstructive pulmonary ventilation dysfunction and positive bronchodilation test (FEV1 increased by 16.8%). The chest CT revealed bilateral multiple bronchiectases, pulmonary bulla, and atelectasis in the right middle lung lobe (Figure 1B). Based on these data, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. Oral voriconazole 200 mg two times daily and methylprednisolone 16 mg per day plus inhaler were prescribed but were demonstrated to be insufficient without the improvement of symptoms. Since February 2021, she was given omalizumab 600 mg three times every month; she was readmitted due to the aggravation of cough and wheezing. The patient denied any history of food or drug allergies. Her family history was negative for any inherited genetic diseases.
On physical examination, her body weight was 58 kg on admission. She exhibited facial flushing, a full moony face, buffalo back, and mossy skin changes on the scalp. Moist rales could be heard on bilateral lung fields. Her laboratory findings on admission revealed moderate C-reactive protein level (33.6 mg/l, reference range: 0-6 mg/l) and a normal level of leukocyte count and erythrocyte sedimentation. Serum IgE was above normal (770 IU/ml, reference range: <130 IU/ml); serum -beta-D-glucan test, galactomannan test, anti-nuclear antibody, anti-neutrophil cytoplasmic antibodies, vasculitis antibodies, antiphospholipid antibodies, antibodies to extractable nuclear antigens, and rheumatoid factor were negative. Pulmonary CT suggested diffuse multiple ground glass shadows and scattered striae in both lungs and more cystic lesions than previously observed (Figure 1C). Bronchoscopy showed viscous jelly-like secretions in the tracheal lumen. The next-generation sequence (NGS) of BALF indicated Pneumocystis jirovecii (sequence reads 34909), Human Herpes Virus Type 5 (also named CMV, sequence reads 1843), and Human Herpes Virus Type 4 (also named EBV, sequence reads 7). With classic diffuse ground-glass lesions appearing in the chest CT images and high sequence reads of CMV and P. jirovecii in BALF detected by mNGS, we identified that the patient had CMV and P. jirovecii coinfection. The sequence reads of EBV, which is ubiquitous in most of the population, were too few to be identified as pathogenic. SMZ-TMP and ganciclovir were given and symptoms were gradually relieved (Figure 2).
Given that the young patient was predisposed to multiple pathogens, including some opportunistic strains, we carefully reviewed the patient's medical history. Surprisingly, she had multiple skin rashes and pruritus all over the body since childhood. A minor traumatic fracture of the right calf occurred at the age of 12. She underwent cutaneous abscesses requiring incision and drainage at 13 years of age. The patient also had a previous diagnosis of pelvic abscess, tubal occlusion, and primary infertility. The patient had recurrent infections of different strains including opportunistic pathogens in multiple organs, skin rashes, and markedly elevated IgE levels. HIES were suspected, and she scored 45 points on the National Institutes of Health clinical HIES scoring system. Further whole-exome sequencing (WES) was performed to screen potential mutations, indicating a heterozygous missense mutation in exon 15 of STAT3 (c.1294G>T, g.62382G>T, p.Val432Leu, NM_139276.2). Consequently, the final diagnosis was made as AD-HIES. Her parents and younger sister are wild-type genotypes. In addition to the standard anti-infection therapy, we prescribed omalizumab 300 mg every 2 weeks and Seretide inhalation. Oral corticosteroids gradually reduced and stopped. During 6 months of follow-up, the patient did not experience recurrent infection. After an initial fluctuation of the level, serum IgE remained stable recently. The patient's symptoms and lung function improved on therapy (Figure 3). The chest CT scan demonstrated improved infiltrates (Figure 1D). | stat3 gene, allergy bronchopulmonary aspergillosis, case report, hyper-ige syndrome, omalizumab | Pulmonary imaging by CT scan. (A) December 2015: multiple cavitary lesions and multiple patchy shadows in both the upper lungs and the dorsal segment of the left lower lung, with bronchiectases in the right middle lung and the lingual and dorsal segments of the left upper and left lower lung. |
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PMC9114644_01 | Female | 28 | A 28-year-old woman was admitted to the Second Xiangya Hospital of Central South University, Hunan, China because of recurrent cough for 6 years and wheezing for 7 months, which aggravated for half a month in May 2021. The patient started to cough sputum early in September 2014, and pulmonary tuberculosis was considered the reason at the local hospital and therefore anti-tuberculosis was given. The symptoms improved significantly until 2015; the patient complained of cough with fever during the anti-tuberculosis therapy and visited our hospital for the first time. Laboratory tests showed an elevated level of leukocyte count, erythrocyte sedimentation rate, C-reactive protein level, and serum total IgE (2,500 IU/ml, normal range: <130 IU/ml). The chest CT revealed multiple cavitary lesions in both upper lungs and the dorsal segment of the left lower lung and bronchiectasis of bilateral lobes (Figure 1A). A combined infection of aspergillosis and Staphylococcus aureus was confirmed by positive culture of both sputum and bronchoalveolar lavage fluid (BALF). Anti-infection with teicoplanin and itraconazole was prescribed, and her symptoms were relieved on therapy. The patient remained stable until 2019; she began coughing intermittently and the symptoms gradually worsened when accompanied with dyspnea and wheezing. She visited our hospital for the second time in December 2020. Blood tests showed a moderately elevated level of eosinophil count (0.97 x 109/L, normal range: 0.02-0.52 x 109/L) and a markedly increased serum total IgE level (>2,500 IU/ml). Total levels of aspergillosis-specific IgE, IgM, and IgG were above normal. A pulmonary function test revealed decreased FVC (2.41 L; expected value: 2.92 L), decreased FEV1 (1.54 L, expected value: 2.53 L), and decreased FEV1/FVC (63.68%, expected value: 84.52%), indicating moderate obstructive pulmonary ventilation dysfunction and positive bronchodilation test (FEV1 increased by 16.8%). The chest CT revealed bilateral multiple bronchiectases, pulmonary bulla, and atelectasis in the right middle lung lobe (Figure 1B). Based on these data, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. Oral voriconazole 200 mg two times daily and methylprednisolone 16 mg per day plus inhaler were prescribed but were demonstrated to be insufficient without the improvement of symptoms. Since February 2021, she was given omalizumab 600 mg three times every month; she was readmitted due to the aggravation of cough and wheezing. The patient denied any history of food or drug allergies. Her family history was negative for any inherited genetic diseases.
On physical examination, her body weight was 58 kg on admission. She exhibited facial flushing, a full moony face, buffalo back, and mossy skin changes on the scalp. Moist rales could be heard on bilateral lung fields. Her laboratory findings on admission revealed moderate C-reactive protein level (33.6 mg/l, reference range: 0-6 mg/l) and a normal level of leukocyte count and erythrocyte sedimentation. Serum IgE was above normal (770 IU/ml, reference range: <130 IU/ml); serum -beta-D-glucan test, galactomannan test, anti-nuclear antibody, anti-neutrophil cytoplasmic antibodies, vasculitis antibodies, antiphospholipid antibodies, antibodies to extractable nuclear antigens, and rheumatoid factor were negative. Pulmonary CT suggested diffuse multiple ground glass shadows and scattered striae in both lungs and more cystic lesions than previously observed (Figure 1C). Bronchoscopy showed viscous jelly-like secretions in the tracheal lumen. The next-generation sequence (NGS) of BALF indicated Pneumocystis jirovecii (sequence reads 34909), Human Herpes Virus Type 5 (also named CMV, sequence reads 1843), and Human Herpes Virus Type 4 (also named EBV, sequence reads 7). With classic diffuse ground-glass lesions appearing in the chest CT images and high sequence reads of CMV and P. jirovecii in BALF detected by mNGS, we identified that the patient had CMV and P. jirovecii coinfection. The sequence reads of EBV, which is ubiquitous in most of the population, were too few to be identified as pathogenic. SMZ-TMP and ganciclovir were given and symptoms were gradually relieved (Figure 2).
Given that the young patient was predisposed to multiple pathogens, including some opportunistic strains, we carefully reviewed the patient's medical history. Surprisingly, she had multiple skin rashes and pruritus all over the body since childhood. A minor traumatic fracture of the right calf occurred at the age of 12. She underwent cutaneous abscesses requiring incision and drainage at 13 years of age. The patient also had a previous diagnosis of pelvic abscess, tubal occlusion, and primary infertility. The patient had recurrent infections of different strains including opportunistic pathogens in multiple organs, skin rashes, and markedly elevated IgE levels. HIES were suspected, and she scored 45 points on the National Institutes of Health clinical HIES scoring system. Further whole-exome sequencing (WES) was performed to screen potential mutations, indicating a heterozygous missense mutation in exon 15 of STAT3 (c.1294G>T, g.62382G>T, p.Val432Leu, NM_139276.2). Consequently, the final diagnosis was made as AD-HIES. Her parents and younger sister are wild-type genotypes. In addition to the standard anti-infection therapy, we prescribed omalizumab 300 mg every 2 weeks and Seretide inhalation. Oral corticosteroids gradually reduced and stopped. During 6 months of follow-up, the patient did not experience recurrent infection. After an initial fluctuation of the level, serum IgE remained stable recently. The patient's symptoms and lung function improved on therapy (Figure 3). The chest CT scan demonstrated improved infiltrates (Figure 1D). | stat3 gene, allergy bronchopulmonary aspergillosis, case report, hyper-ige syndrome, omalizumab | Pulmonary imaging by CT scan. (B) December 2020: multiple cystic and columnar dilated bronchial shadows of variable size in both lungs, with exudative foci in the middle lobe of the right lung. |
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PMC9114644_01 | Female | 28 | A 28-year-old woman was admitted to the Second Xiangya Hospital of Central South University, Hunan, China because of recurrent cough for 6 years and wheezing for 7 months, which aggravated for half a month in May 2021. The patient started to cough sputum early in September 2014, and pulmonary tuberculosis was considered the reason at the local hospital and therefore anti-tuberculosis was given. The symptoms improved significantly until 2015; the patient complained of cough with fever during the anti-tuberculosis therapy and visited our hospital for the first time. Laboratory tests showed an elevated level of leukocyte count, erythrocyte sedimentation rate, C-reactive protein level, and serum total IgE (2,500 IU/ml, normal range: <130 IU/ml). The chest CT revealed multiple cavitary lesions in both upper lungs and the dorsal segment of the left lower lung and bronchiectasis of bilateral lobes (Figure 1A). A combined infection of aspergillosis and Staphylococcus aureus was confirmed by positive culture of both sputum and bronchoalveolar lavage fluid (BALF). Anti-infection with teicoplanin and itraconazole was prescribed, and her symptoms were relieved on therapy. The patient remained stable until 2019; she began coughing intermittently and the symptoms gradually worsened when accompanied with dyspnea and wheezing. She visited our hospital for the second time in December 2020. Blood tests showed a moderately elevated level of eosinophil count (0.97 x 109/L, normal range: 0.02-0.52 x 109/L) and a markedly increased serum total IgE level (>2,500 IU/ml). Total levels of aspergillosis-specific IgE, IgM, and IgG were above normal. A pulmonary function test revealed decreased FVC (2.41 L; expected value: 2.92 L), decreased FEV1 (1.54 L, expected value: 2.53 L), and decreased FEV1/FVC (63.68%, expected value: 84.52%), indicating moderate obstructive pulmonary ventilation dysfunction and positive bronchodilation test (FEV1 increased by 16.8%). The chest CT revealed bilateral multiple bronchiectases, pulmonary bulla, and atelectasis in the right middle lung lobe (Figure 1B). Based on these data, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. Oral voriconazole 200 mg two times daily and methylprednisolone 16 mg per day plus inhaler were prescribed but were demonstrated to be insufficient without the improvement of symptoms. Since February 2021, she was given omalizumab 600 mg three times every month; she was readmitted due to the aggravation of cough and wheezing. The patient denied any history of food or drug allergies. Her family history was negative for any inherited genetic diseases.
On physical examination, her body weight was 58 kg on admission. She exhibited facial flushing, a full moony face, buffalo back, and mossy skin changes on the scalp. Moist rales could be heard on bilateral lung fields. Her laboratory findings on admission revealed moderate C-reactive protein level (33.6 mg/l, reference range: 0-6 mg/l) and a normal level of leukocyte count and erythrocyte sedimentation. Serum IgE was above normal (770 IU/ml, reference range: <130 IU/ml); serum -beta-D-glucan test, galactomannan test, anti-nuclear antibody, anti-neutrophil cytoplasmic antibodies, vasculitis antibodies, antiphospholipid antibodies, antibodies to extractable nuclear antigens, and rheumatoid factor were negative. Pulmonary CT suggested diffuse multiple ground glass shadows and scattered striae in both lungs and more cystic lesions than previously observed (Figure 1C). Bronchoscopy showed viscous jelly-like secretions in the tracheal lumen. The next-generation sequence (NGS) of BALF indicated Pneumocystis jirovecii (sequence reads 34909), Human Herpes Virus Type 5 (also named CMV, sequence reads 1843), and Human Herpes Virus Type 4 (also named EBV, sequence reads 7). With classic diffuse ground-glass lesions appearing in the chest CT images and high sequence reads of CMV and P. jirovecii in BALF detected by mNGS, we identified that the patient had CMV and P. jirovecii coinfection. The sequence reads of EBV, which is ubiquitous in most of the population, were too few to be identified as pathogenic. SMZ-TMP and ganciclovir were given and symptoms were gradually relieved (Figure 2).
Given that the young patient was predisposed to multiple pathogens, including some opportunistic strains, we carefully reviewed the patient's medical history. Surprisingly, she had multiple skin rashes and pruritus all over the body since childhood. A minor traumatic fracture of the right calf occurred at the age of 12. She underwent cutaneous abscesses requiring incision and drainage at 13 years of age. The patient also had a previous diagnosis of pelvic abscess, tubal occlusion, and primary infertility. The patient had recurrent infections of different strains including opportunistic pathogens in multiple organs, skin rashes, and markedly elevated IgE levels. HIES were suspected, and she scored 45 points on the National Institutes of Health clinical HIES scoring system. Further whole-exome sequencing (WES) was performed to screen potential mutations, indicating a heterozygous missense mutation in exon 15 of STAT3 (c.1294G>T, g.62382G>T, p.Val432Leu, NM_139276.2). Consequently, the final diagnosis was made as AD-HIES. Her parents and younger sister are wild-type genotypes. In addition to the standard anti-infection therapy, we prescribed omalizumab 300 mg every 2 weeks and Seretide inhalation. Oral corticosteroids gradually reduced and stopped. During 6 months of follow-up, the patient did not experience recurrent infection. After an initial fluctuation of the level, serum IgE remained stable recently. The patient's symptoms and lung function improved on therapy (Figure 3). The chest CT scan demonstrated improved infiltrates (Figure 1D). | stat3 gene, allergy bronchopulmonary aspergillosis, case report, hyper-ige syndrome, omalizumab | Pulmonary imaging by CT scan. (C) 8 May 2021: diffuse multiple ground glass shadows and scattered striae in both lungs and more cystic lesions than previously observed. |
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PMC9114644_01 | Female | 28 | A 28-year-old woman was admitted to the Second Xiangya Hospital of Central South University, Hunan, China because of recurrent cough for 6 years and wheezing for 7 months, which aggravated for half a month in May 2021. The patient started to cough sputum early in September 2014, and pulmonary tuberculosis was considered the reason at the local hospital and therefore anti-tuberculosis was given. The symptoms improved significantly until 2015; the patient complained of cough with fever during the anti-tuberculosis therapy and visited our hospital for the first time. Laboratory tests showed an elevated level of leukocyte count, erythrocyte sedimentation rate, C-reactive protein level, and serum total IgE (2,500 IU/ml, normal range: <130 IU/ml). The chest CT revealed multiple cavitary lesions in both upper lungs and the dorsal segment of the left lower lung and bronchiectasis of bilateral lobes (Figure 1A). A combined infection of aspergillosis and Staphylococcus aureus was confirmed by positive culture of both sputum and bronchoalveolar lavage fluid (BALF). Anti-infection with teicoplanin and itraconazole was prescribed, and her symptoms were relieved on therapy. The patient remained stable until 2019; she began coughing intermittently and the symptoms gradually worsened when accompanied with dyspnea and wheezing. She visited our hospital for the second time in December 2020. Blood tests showed a moderately elevated level of eosinophil count (0.97 x 109/L, normal range: 0.02-0.52 x 109/L) and a markedly increased serum total IgE level (>2,500 IU/ml). Total levels of aspergillosis-specific IgE, IgM, and IgG were above normal. A pulmonary function test revealed decreased FVC (2.41 L; expected value: 2.92 L), decreased FEV1 (1.54 L, expected value: 2.53 L), and decreased FEV1/FVC (63.68%, expected value: 84.52%), indicating moderate obstructive pulmonary ventilation dysfunction and positive bronchodilation test (FEV1 increased by 16.8%). The chest CT revealed bilateral multiple bronchiectases, pulmonary bulla, and atelectasis in the right middle lung lobe (Figure 1B). Based on these data, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. Oral voriconazole 200 mg two times daily and methylprednisolone 16 mg per day plus inhaler were prescribed but were demonstrated to be insufficient without the improvement of symptoms. Since February 2021, she was given omalizumab 600 mg three times every month; she was readmitted due to the aggravation of cough and wheezing. The patient denied any history of food or drug allergies. Her family history was negative for any inherited genetic diseases.
On physical examination, her body weight was 58 kg on admission. She exhibited facial flushing, a full moony face, buffalo back, and mossy skin changes on the scalp. Moist rales could be heard on bilateral lung fields. Her laboratory findings on admission revealed moderate C-reactive protein level (33.6 mg/l, reference range: 0-6 mg/l) and a normal level of leukocyte count and erythrocyte sedimentation. Serum IgE was above normal (770 IU/ml, reference range: <130 IU/ml); serum -beta-D-glucan test, galactomannan test, anti-nuclear antibody, anti-neutrophil cytoplasmic antibodies, vasculitis antibodies, antiphospholipid antibodies, antibodies to extractable nuclear antigens, and rheumatoid factor were negative. Pulmonary CT suggested diffuse multiple ground glass shadows and scattered striae in both lungs and more cystic lesions than previously observed (Figure 1C). Bronchoscopy showed viscous jelly-like secretions in the tracheal lumen. The next-generation sequence (NGS) of BALF indicated Pneumocystis jirovecii (sequence reads 34909), Human Herpes Virus Type 5 (also named CMV, sequence reads 1843), and Human Herpes Virus Type 4 (also named EBV, sequence reads 7). With classic diffuse ground-glass lesions appearing in the chest CT images and high sequence reads of CMV and P. jirovecii in BALF detected by mNGS, we identified that the patient had CMV and P. jirovecii coinfection. The sequence reads of EBV, which is ubiquitous in most of the population, were too few to be identified as pathogenic. SMZ-TMP and ganciclovir were given and symptoms were gradually relieved (Figure 2).
Given that the young patient was predisposed to multiple pathogens, including some opportunistic strains, we carefully reviewed the patient's medical history. Surprisingly, she had multiple skin rashes and pruritus all over the body since childhood. A minor traumatic fracture of the right calf occurred at the age of 12. She underwent cutaneous abscesses requiring incision and drainage at 13 years of age. The patient also had a previous diagnosis of pelvic abscess, tubal occlusion, and primary infertility. The patient had recurrent infections of different strains including opportunistic pathogens in multiple organs, skin rashes, and markedly elevated IgE levels. HIES were suspected, and she scored 45 points on the National Institutes of Health clinical HIES scoring system. Further whole-exome sequencing (WES) was performed to screen potential mutations, indicating a heterozygous missense mutation in exon 15 of STAT3 (c.1294G>T, g.62382G>T, p.Val432Leu, NM_139276.2). Consequently, the final diagnosis was made as AD-HIES. Her parents and younger sister are wild-type genotypes. In addition to the standard anti-infection therapy, we prescribed omalizumab 300 mg every 2 weeks and Seretide inhalation. Oral corticosteroids gradually reduced and stopped. During 6 months of follow-up, the patient did not experience recurrent infection. After an initial fluctuation of the level, serum IgE remained stable recently. The patient's symptoms and lung function improved on therapy (Figure 3). The chest CT scan demonstrated improved infiltrates (Figure 1D). | stat3 gene, allergy bronchopulmonary aspergillosis, case report, hyper-ige syndrome, omalizumab | Pulmonary imaging by CT scan. (D) 18 August 2021: improved infiltrations and multilobed segmental bronchiectases and bullae in both lungs. |
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PMC2808612_01 | Male | 65 | A 65-yr-old male patient was admitted to Chonnam National University Hospital because of fever and chills with drowsy mental status after hemodialysis. His symptoms and signs were acute onset. Fifteen years earlier, he was found to have diabetes and well controlled by insulin and oral hypoglycemics, and to have hypertension. Five years earlier, he had developed chronic renal failure due to diabetic complication. Three years earlier, he was operated native brachiocephalic arteriovenous fistula formation on his left arm and has been taken maintenance hemodialysis with 3 sessions in each week. Other past medical history including tuberculosis, hepatitis or abdominal surgery had not been known. He was non-smoker, and non-alcoholics. There was no history of trauma. His blood pressure was 130/80 mmHg and his body temperature was 38.1C on admission. On physical examination, there was diffuse tenderness on the abdomen, especially on the left hypochondrium. There was ecchymosis around the left brachiocephalic arteriovenous fistula area with tenderness and swelling. Auscultation of his chest revealed diastolic cardiac murmurs on apex.
On chest radiography and electrocardiogram, there was cardiomegaly. Biochemical analysis revealed that hemoglobin level was 8.2 g/dL, white blood cell count 11,500/microL, platelet count 84,000/microL, blood urea nitrogen level 25.0 mg/dL, and serum creatinine level 4.6 mg/dL, sodium 140 mEq/L, potassium 4.7 mEq/L, chloride 97 mEq/L, aspartate aminotransferase 28 IU/L, alkaline phosphatase 81 IU/L, serum albumin 3.4 g/dL, C-reactive protein 25.97 mg/dL, erythrocyte sedimentation rate 31 mm/hr, fibrinogen degradation product <5 microg/mL, D-dimer 0.4 mg/L (reference value 0-0.3), aPTT 37.3 sec, PT 13.1 sec/INR 1.08, and fibrinogen 716 mg/dL.
Abdominal sonography revealed two hypoechoic space occupying lesions and one cystic lesion in the spleen (Fig. 1). To differentiate splenic abscess or infarction, abdominal computed tomography (CT) was performed. Abdominal CT revealed multiple septated cystic lesions in the spleen, the largest 4.3 cm, and 2 cm low attenuated lesion in the left buttock area, compatible with multiple splenic abscesses and an abscess in the left buttock area (Fig. 2). We performed 2D-echocardiography, and found mobile hyperechoic mass on posterior mitral valve leflet tip with calcified valve. His brain CT was normal. We obtained blood samples at two different sites for bacteriologic culture and then started empirical antibiotics with ceftriaxone and aminoglycoside. He had continuous fever and left hypochondrial pain. Blood culture revealed methicillin sensitive Staphylococcus aureus (MSSA). We changed the antibiotics with cefazoline based on the drug sensitivity test. Inflammatory signs and hypoechoic lesions in the spleen did not respond to antibiotic therapy. On the 4th hospital day, emergency splenectomy was performed for the splenic abscess based on blood culture and abdominal CT. We aspirated blood from the evacuated spleen for bacteriologic culture and sent the evacuated spleen to pathologist for histologic diagnosis (Fig. 3). MSSA was cultured from the evacuated splenic blood, too. The pathologic findings showed splenic abscesses and infarction (Fig. 4). Antibiotic therapy was continued and he became afebrile. CBC findings and other chemical laboratory findings were returned to normal. | null | Not supported with pagination yet | null |
PMC3861848_01 | Female | 50 | A 50-year-old female was diagnosed with FA in 1993, at the age of 31. At the age of 16, she was referred from the school physician to a pediatrician for the first time because of a subtle gait ataxia. Neurological examination revealed areflexia, muscular hypotonia, reduced position and vibration sense in the lower limbs. A few years later, she presented with an aggravated spastic gait ataxia, postural ataxia and dysarthria as well as urinary and fecal incontinence. At the age of 30, the patient was no longer able to walk and has been confined to a wheelchair ever since. A few years later, she underwent colectomy and received a suprapubic catheter. She started taking idebenone, a drug that has shown a positive effect on neurological functions in patients with FA. Her parents were first cousins. The diagnosis of FA was confirmed genetically by a DNA analysis showing that the patient was homozygous for an expansion of GAA in the frataxin gene corresponding to 900 repeats. The serum alpha-tocopherol level was normal.
In August 2010, the patient presented to the Department of Neurology, Uppsala University, for her annual visit. She reported frequent and very painful flexor spasms in the lower limbs and trunk. Her sleep was interrupted because of such spasms awakening her throughout the night. Changing the position of her body in the bed or wheelchair, exposing herself to the cold, laughing, coughing, sneezing or taking a shower elicited the spasms, which at times lasted for more than 1 h. Different analgesic drugs including oxycodone, diclofenac and pregabalin were tried without any effect. The combination of oral baclofen in a high dose of 80 mg per day and botulinum toxin injections in the adductor muscles did not improve her painful spasms.
On examination, the patient had a pronounced dysarthria, upper and lower limb ataxia, bilateral foot drop, absent tendon reflexes in all four limbs, and the plantar reflexes were extensor. There was a loss of proprioception and vibration sense in the lower limbs. Muscle tone was not increased in the limbs, and the strength in her arms was preserved. According to the modified Ashworth score, the patient had no spasticity. The spasms were provoked by hip flexion and stretching the legs and lasted for a few minutes, causing great distress to the patient.
The patient received an ITB test injection of 25 microg on the first day of testing. The response was remarkable: the painful spasms totally disappeared only 1 h after the injection, and this positive response lasted for 7 h. During this period, we tried to provoke the spasms by changing her body position, stretching her legs and exposing her to the cold, but none of these maneuvers led to spasms or pain. No side effects were noted during the testing procedure, and we decided to implant an ITB-delivering pump. For the past 2 years, our patient has been on continuous ITB at a constant dose of 100 microg per day with preserved efficacy. She experienced great relief of her symptoms and was very satisfied with the result. | friedreich ataxia, intrathecal baclofen, spasms | Not supported with pagination yet | null |
PMC6287400_01 | Male | 52 | A 52-year-old taxi driver was suffering from chronic back pain from 10 years. During the last 3 years, his back pain became progressively worse and developed numbness in both lower limbs.
Following the consultation of neurologist at a hospital at Kandy, a computed tomography (CT) was done in 2012 and diagnosed as infective spondylitis at D5/D6 level of the dorsal spine. It was identified as Pott's disease (spinal tuberculosis). Anti-tubercular therapy (ATT), was given for 1-year period. After ATT, the patient was unable to walk without support. After that, he was referred to neurology unit. While he was in neurology unit, he suffered accidental fall from the bed causing him unable to move his lower limbs, but his sphincter control was intact (sensory intact with motor defect). Repeated CT of dorsal spine showed D5/D6 fracture [Figure 1a]. Since his condition did not improved, he was asked to take follow-up at the rehabilitation unit for conservative management, which was continued up to 1 year at rehabilitation unit. Observing no improvement, the patient decided to seek Ayurveda treatment starting from June 2013.
At the time of reporting for Ayurvedic consultation and management, patient complained of a heaviness and numbness over lower body and difficulty to move his legs. He could not bend and raise his lower limbs. The patient was treated using three treatment regimens while assessing the outcome at the end of each regimen.
Treatment regimen 1 (1-6 months): Sheethodaka oil (30 ml) with paste of Katakaladi (Bridelia retusa [L.] A. Juss) was applied externally over the fractured area. Triphala decoction (30 ml), Vasa-Guduchi decoction (120 ml) and Gandharva-Hastadi decoction (120 ml) was administered orally twice a day, for first 3 months of this phase [Table 1]. After 1 month and when the patient showed first signs of improvement [Table 2], simultaneously passive exercises were started. Active exercises were started later, when further recovery was noted
Treatment regimen 2 (6-12 months): Triphala decoction (30 ml) treatment was continued for next 6 months in the same dose similar to first 6 months. In addition to that, Pinda oil (30 ml) with paste of Katakala (60 g) was applied topically daily. Dantimooladi decoction 120 ml was administered twice a day in the first 3 months of this phase. In the second 3-month period, Dashamoola-Bala-Eranda decoction (120 ml) was given. The patient recovered from symptoms of numbness and heaviness along with gaining ability to move his lower limbs
Treatment regimen 3 (12-24 months): During this period, Tarpana Chikitsa which was continued throughout 12-month period along with application of Narayana oil (30 ml) with paste of Ashwagandhadi (60 g), externally. Maharasnadi decoction (120 ml) was administered twice a day at initial 3 months of this phase and after that Masha-Baladi decoction (120 ml) was started twice a day for the remaining 9 months.
The fractured bone was immobilized using lumbar thoracic corset. It was applied throughout the day in the 1st year and after that until the treatment concludes it was applied over the day time only. Altogether, after 24 months of commencing initial treatment, the patient recovered completely.
Seethodaka oil was prepared according to the classical text of Ayurveda Pharmacopeia. Pinda oil and Narayana oil were prepared according to the classical text Bhaishajya Ratnavali. Triphala decoction, Vasa-Guduchi decoction, Gandharava-Hastadi decoction, Dantimooladi decoction, Dashamoola-Bala-Erandadi decoction, Maharasnadi decoction and Masha-Baladi decoction were prepared according to the guidelines and methods mentioned by the classical text of Ayurveda Pharmacopeia.
Paste of Katakaladi and paste of Ashwagandhadi were prepared according to the guidelines of Sri Lankan traditional physician family of "Arangala Veda Parapura." Preparation of paste of Katakaladi: 240 ml of juice extracted from bark of each drugs Bridelia retusa (L.) A. Juss. (Katakala), Syzygium cumini (Linn) skeel's (Jambu) and root of Hemidesmus indicus (L.) R. Br. (Sariva) and 30 g of each powdered rhizomes of Zingiber officinale Roscoe (Shunthi), fruits of Piper longum Linn (Pippali), stem of Coscinium fenestratum (Gaertn.) Colebr. (Daruharidra), pericarp of Terminalia chebula Retz (Abhaya), Terminalia belerica Roxb (Vibhitaka) and Phyllanthus embillica L. (Dhatri) were added together and heated over mid fire until a semi solid paste is obtained. Preparation of paste of Ashwagandhadi: Powder of Withania somnifera (L.) Dunal. (Ashwagandha, 60 g), powder of Vigno mungo Linn (Masha, 30 g), Cinnamomum zeylanicam blume (Twak, 15 g) and powder of Syzygium aromaticam (L.) Merr. and Perry (Lavanga 15 g) were grinded with 120 ml egg white and mixed with 60 ml of honey to obtain semi-solid paste.
Images of CT scan of fracture site before [Figure 1a] and after the Ayurveda treatment [Figure 1b].
Motor function assessment with the time, after commencing the Ayurveda treatment [Table 2].
Quality of life was assessed before the treatment, 1 month, 3 months, 6 months, 1 year, 18 months and 3 years of the treatment. Quality of Life was assessed by the ferrans and powers quality of life index (FPQLI) spinal cord injury version-III.
At the commencement of treatment, the total quality of life score was 84/420. Following 3 months, the 4 subscales increased significantly (P < 0.05). After 24 months of commencing the treatment, the patient recovered and the total score of FPQLI became 410/420 (P = 0.02) [Table 3].
Statistical analysis was conducted using Wilcoxon signed rank test. Statistical software SAS version 9.1 (New Jersey, USA. 2005) was used for the analysis. Initially, from 1 to 6-month period, the parameters were compared at 3-month intervals. After 6 months, until completion of treatment, it was compared at 6-month intervals. | ayurveda, motor dysfunction, physiotherapy and quality of life, spinal fracture | Not supported with pagination yet | null |
PMC8502119_01 | Male | 0 | We present a case of an 18-month-old boy, born of a non-consanguineous marriage and by normal vaginal delivery, with a birth weight of 3 kg and an uneventful perinatal period. The child had normal development and was fully immunized for age till then. The mother had no history of fever, jaundice, and pruritis during the antenatal period. The child presented with yellowish discoloration of the eyes and urine for 3 months and disabling pruritis for 2 months. The mother also recalled four episodes of bilateral nose bleeds in the past 3 months and occasional gum bleeds. She had also noticed that child was passing black tarry stool for the last 2 weeks.
On physical examination, no dysmorphic features were found, and the child weighed 8.5 kg (-2.11 Z-score), stand 74 cm ( - 2.46 Z-score), and appeared pale and icteric. His abdomen was distended with tenderness in the right upper quadrant. Veins and sinuses were not dilated. Multiple pruritic scar marks were seen. The edge of the liver edge was palpable 4 cm below the right costal margin. Ophthalmology opinion was taken for examination of Kayser Fleischer rings, and the result was negative.
Initial laboratory findings (Table 1) revealed severe microcytic hypochromic anemia with hemoglobin of 5.6 g/dL and elevated liver enzymes [alkaline phosphatase (ALP), 1589 U/L; aspartate transaminase (AST), 288 U/L; alanine transaminase (ALT), 173 U/L; gamma-glutamyl transferase (GGT), 84 U/L; albumin, 47 g/L; lactate dehydrogenase (LDH), 132 IU/L; total bilirubin, 14.8 mg/dL; conjugated bilirubin, 12.2 mg/dL; serum bile acid, 170 mol/L; vitamin D3, 6.91 ng/mL]. Serum electrolytes, calcium, magnesium, phosphate, urea and creatinine, thyroid stimulating hormone, and C-reactive protein were within the normal limits. The serum lipase level was 34 U/L. Hemoglobinopathy screening was performed to investigate the cause of jaundice, and the result was negative. Iron panel confirmed iron deficiency (serum iron, 4 mol/L; (total iron-binding capacity, 90 mol/L; transferrin saturation, 0.04%; and ferritin, 5 g/L). Serum protein electrophoresis was performed to rule out autoimmune hepatitis, which did not show dominant protein bands. Alpha-1 antitrypsin level was 2.2 mumol/L. Results of the serological workup for infective etiologies (such as hepatitis B, hepatitis C, Epstein-Barr virus, cytomegalovirus, parvovirus B19, and syphilis) were negative. Three urine samples were sent for non-reducing sugars, and 2 of 3 were positive. To rule out metabolic causes of infantile jaundice, metabolic screening was performed for tyrosinemia, galactosemia, and hereditary fructose intolerance, and the result was negative.
Ultrasonography (USG) of the abdomen revealed an enlarged liver with increased nodularity (Figure 1). Gross ascites and mild splenomegaly were present. USG showed normal gallbladder, common bile duct, and portal veins. Findings of magnetic resonance cholangiopancreatography were normal. For severe anemia, he was transfused with two units of packed cells, and the post-transfusion hemoglobin level was 9.3 g/dL.
To evaluate the cause of melena, upper gastrointestinal endoscopy was performed under general anesthesia, which revealed gastric fundal varices (Figure 2), and four bands were applied. He was started on ursodeoxycholic acid, ondansetron, and rifampicin for pruritus. Vitamin A, D, E, and K supplementations were given. Spironolactone and nadolol were added for portal hypertension. Paracentesis was performed on the third day of admission. Peritoneal fluid cultures were negative for tuberculosis, bacterial growth, or fungus. Biochemical analysis of peritoneal fluid was not contributory and was negative for malignant cells. As the etiology of jaundice was still unclear, USG-guided liver biopsy was taken, which showed intrahepatic cholestasis with moderate fibrosis and inflammatory cells (Figure 3); hence, a preliminary diagnosis of progressive intrahepatic cholestasis (PFIC) was made.
Considering the possibility of an inherited disorder, genetic tests for ABCB11, ABCB4, ATP8B1, JAG1, NOTCH2, and TJP2 were performed and revealed positive results for ABCB11 confirming the diagnosis to be PFIC type 2.
After getting the definitive diagnosis, the parents were counseled regarding the surgical treatment options, which included nasobiliary drainage, partial external biliary diversion (PEBD), partial internal biliary diversion (PIBD), ileal exclusion, and liver transplantation. After obtained informed consent, the child was taken for PIBD with a cholecystojejunocolic anastomosis. Intraoperatively, a 10-cm loop of bowel was isolated from the mid jejunum, and this conduit was sutured in an isoperistaltic manner, inferiorly to the anterior aspect of the ascending colon and superiorly to the gall bladder. The full thickness of gallbladder was anastomosed to the serosa of the conduit in a single layer. A single layer of serosa-to-serosa anastomosis was performed between the conduit and the colon. The distal end of the jejunum was tapered, and an intussuscepted nipple valve was introduced prior to anastomosing to the colon to prevent colonic contents from entering the conduit. The postoperative period was uneventful, and the child was discharged on postoperative day 12 on oral medications.
Jaundice and pruritus were assessed by 5-D itch score in the postoperative period and follow-up visits, which showed marked reduction in pruritis. On 10 weeks follow-up, the patient was asymptomatic, with biochemical investigations (Table 2) showing total bilirubin level of 3 mg/dL, conjugated bilirubin of 1.7 mg/dL, ALP of 250 U/L, AST of 42 IU/L, ALT of 65 IU/L, and serum bile acid of 60 mumol/l. In addition, the child was gaining weight and height. Although parents complained of intermittent diarrhea, it can be attributed to the high bile salt content in the intestine. | end stage liver disease, molecular chaperones, partial internal biliary diversion, portal gastropathy, progressive familial intrahepatic cholestasis | Not supported with pagination yet | null |
PMC9897069_03 | Male | 29 | A 29-year-old man was referred by the Department of Internal Medicine regarding lesions in his oral cavity. He complained about pain in the lower anterior jaw gum and lower lip for a week and had a fever history in the last 2 weeks. He was diagnosed by the Internist with HIV stage IV with wasting syndrome, hypothyroidism, latent syphilis, chronic hepatitis B, moderate dehydration et causa inadequate intake, stage 1 acute kidney injury (AKI), inflammatory anemia, and malnutrition. On extra oral examination, we found exfoliative lips, and the lips looked pale. From the intra-oral examination, we found multiple irregular painful erosion on the lower labial mucosa. The anterior mandibular gingiva was edematous and tended to bleed and there was an excruciating grayish-white plaque in the region of teeth 33 to 43 (Figure 3). On the upper anterior gingiva, reddish bands appeared on the attached gingiva of teeth 11 and 21 (Figure 3). Laboratory examinations showed reactive TPHA with titer 1:5120 and reactive VDRL with titer 1:64, reactive hepatitis B e antigen (HBeAg), reactive HBsAg, non-reactive anti-hepatitis c virus (HCV). Examination of Mycobacterium tuberculosis using the Assay method did not find Mycobacterium tuberculosis bacteria. The lesions on the gingiva were diagnosed with necrotizing ulcerative gingivitis (NUG). The lesion on the maxillary anterior gingiva was diagnosed as linear gingival erythema.
Necrotizing ulcerative gingivitis in this patient was treated with 1.5% hydrogen peroxide irrigation and rinsed with saline solution. Patients were also asked to rinse their mouth with 0.2% chlorhexidine gluconate 3 times a day and regularly clean their teeth and tongue at least 2 times a day. We did not prescribe any antibiotic because Internal Medicine had given azithromycin for systemic infection. After 7 days of therapy, the lesions improved (Figure 3). | arv-naive patients, covid-19 pandemic, hiv, oral lesions | Not supported with pagination yet | null |
PMC4532120_01 | Male | 31 | A 31-year-old Korean male patient was transferred to our hospital from a local hospital because of persistent melena of undetermined origin. Four months ago, the patient visited the hospital with complaints of chest tightness and productive cough. An X-ray film of the chest at that time showed a patch infiltration in the right lower lung field. Studies of the sputum for acid fast bacilli were negative but anti-tuberculosis medications were started under the impression of pulmonary tuberculosis. Three months later, he was admitted to the same hospital because of melena and underwent extensive work-ups including gastroscopic examination, barium studies of the colon and small bowels, and a gastric mucosa scan for Meckel's diverticulum, but no bleeding focus was found. During the stay in that hospital, the melena improved spontaneously and he was discharged. He did fairly well until 10 days prior to this admission when recurrent melena developed. Additional studies including 99mTC-sulfur colloid scintigraphy were carried out, but no bleeding focus was found.
On admission, the patient appeared pale and acutely ill. The blood pressure was 130/70 mm/Hg, pulse rate 120/min, respiratory rate 20/min, and the temperature 36.5 C. The heart sound was normal without murmur. Breathing sound was decreased at the right lower lung field. No lymphadenopathy was found in the neck or axilla. No palpable abdominal mass was felt. Rectal examination revealed internal hemorrhoid and hematochezia.
The hemoglobin was 4.6 g/dl and the hematocrit was 14%. The white blood cell count was 6300/mm3 and the platelet 203,000/mm3. The urea nitrogen was 22.4 mg/dl, the creatinine 1.5 mg/dl, the protein 2.5 g/dl (the albumin 1.3 g/dl and the globulin 1.2 g/dl), the bilirubin 0.4 mg/dl, the alkaline phosphatase 53 IU, the aspartate aminotransferase (AST) 10 IU, and the alanine aminotransferase (ALT) 10 IU. The serum sodium was 127 mEq/L and the potassium 4.1 mEq/L. Chest X-ray film revealed an ill defined dense infiltrate with air bronchogram in the right lower lung field (Fig. 1). Mesenteric arteriography was performed but could not find any bleeding focus. Because of severe hematochezia, the flexible sigmoidoscopy was not available. The hemorrhoid with massive bleeding was found by anoscopy. An emergency hemorrhoidectomy was carried out on the second hospital day. However, a large amount of hematochezia persisted even after the operation and signs of serious disseminated intravascular coagulopathy (DIC) follwed. On the 10th hospital day while the DIC improved, the patient complained of abdominal distension and pain. Ascites was suspected.
An abdominal paracentesis revealed intraabdominal bleeding. An emergency exploratory laparotomy was perfomed. On operation, multiple polypoid masses of various sizes were palpated intraluminally in the jejunum from 10 cm below the Treitz ligament to the 120 cm distally. A large perforation of the jejunum (8 cm in diameter) probably caused by necrosis of the bowel wall was found on the antemesenteric border of the jejunum 20-25 cm below the Treitz ligament. Multiple mass lesions including hematomes were also found in the mesenteric root of the small intestine. Small bowel resection and end-to-end anastomosis were performed. On section, 36 polypoid masses were scattered grossly along the full length of the resected jejunum. The largest mass was 5.0x8.0x4.0 cm in size and composed of brownish homogeneous materials. Similar materials were filled in the mesenteric arteries and veins (Fig. 2).
Mlicroscopically, numerous hemosiderin pigments were scattered throughout the fields. The cells in the polypoid mass lesion were consistent with large round cells of undetermined origin. Each cell had a round nucleus containing prominent nucleoli. The cytoplasm was homogenous and clear (Fig. 3). The immunohistochemical study for S-100 protein was negative. Electron microscopically, obvious desmosomes were identified as convincing evidence of carcinoma (Fig. 4). Bronchoscopic examination, which was done on the 10th postoperative day, revealed an obstructing round mass at the entrance of the right main bronchus (Fig. 5). Histologically, this lesion was diagnosed as large cell carcinoma of the lung (Fig. 6).
On the 27th postoperative day, massive amounts of hematemesis and hematochezia developed again. The patient died on the 31st postoperative day due to hypovolemic shock. | null | Not supported with pagination yet | null |
PMC8164421_01 | Female | 63 | A 63-year-old elderly female was admitted to our hospital with a lump in her right breast, first noticed two months ago. On clinical examination, a 6x4 cm lump was seen involving the central quadrant, firm to hard in consistency with palpable ipsilateral axillary lymph node. Mammography was suggestive of breast imaging-reporting and data system (BIRADS) category V lesion of the breast. Fine needle aspiration cytology indicated it as ductal malignancy. Furthermore, biopsy confirmed it as grade III intra-ductal carcinoma with ER/PR and HER2-Neu positive malignancy. Eighteen (18)-flurodeoxyglucose positron emission tomography (18-FDG PET) demonstrated a hypermetabolic lobulated soft tissue mass involving outer quadrant of right breast measuring approximately [4.8 x 3.3 x 5 cm SUV max 21.1]. In addition, hypermetabolic right axillary nodes [SUV max 23.8], right internal mammary node [6SUV max 6], mediastinal/hilar and upper abdominal lymphadenopathy [SUV max 17.9] were also seen (Figure 1). Diffuse splenic hypermetabolism was also seen. The patient was planned for neoadjuvant chemotherapy. She received 4 cycles of chemotherapy with AC (Adriamycin and cyclophosphamide) regimen at 3 weeks interval. She tolerated the chemotherapy well. After the fourth cycle, the lump showed a reduction in size to 2 x 2 cm with no palpable axillary lymph nodes. Repeat 18-FDG PET showed near complete metabolic and significant morphologic resolution of previously seen lobulated soft tissue mass involving right breast, now measuring 1.8 cm [SUV max 2.1] and right axillary lymph nodes [SUV max 2.5] was seen. However, there was no gross interval change in size and metabolism of previously seen small supraclavicular, internal mammary, multistation mediastinal/hilar, upper abdominal lymphadenopathy and splenic hypermetabolism. This raised the possibility of an alternate diagnosis. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) was performed to rule out metastasis. Histopathological examination showed epithelioid histiocytes and langerhans type of giant cell suggestive of granulomatous inflammation (Figure 2). No atypical/malignant cells were seen. Interferon gamma release assay (IGRA) for tuberculosis was negative. On further evaluation, angiotensin converting enzyme (ACE) level were found to be elevated (52 IU/L). As she had no pulmonary symptoms, she was not treated for sarcoidosis. Thus, effective management via histopathological examination made sure she did not receive further cycles of unnecessary chemotherapy. | sarcoidosis, breast cancer, case report, intraductal carcinoma, non-caseating granuloma | Not supported with pagination yet | null |
PMC9899364_01 | Female | 80 | Case 1 was an 80-year-old female referred for evaluation of painful oral ulcers. Medical history included fever and cough for the last 2 months, and tuberculosis confirmed by culture of Mycobacterium tuberculosis, with discontinued treatment with rifampicin and isoniazid. Physical examination revealed multiple cutaneous erosive, and erythematous papules with crust formation on the face, an irregular large ulcer on the left breast, an erythematous plaque with yellowish papules on the right arm and necrotic ulcers with crusts on her 3rd left toe. Intra-oral examination revealed multiple ulcers and erythematous plaques in the hard and soft palates, as well as on the dorsum and lateral surfaces of the tongue (Fig. 1). The patient also reported dysphagia, dysphonia, and chronic nasal obstruction, and of note, the death of her cat few months earlier, presenting lesions on the skin. | null | Not supported with pagination yet | null |
PMC9899364_02 | Male | 31 | Case 2 was a 31-year-old HIV-positive male referred for evaluation of multiple cutaneous ulcers. The patient was under anti-retroviral therapy (efavirenz, stavudine and lamivudine), with CD4 count of 114 cells/mm3 and viral load of 76,023 copies/ml. He also reported use of tobacco and alcohol. Upon physical examination, multiple cutaneous ulcers with elevated margins and crust formation were observed on the face, chest, and upper limbs. Intra-oral examination showed diffuse superficial granular ulcers of moriform surface and variable size, located in the hard/soft palate, gingivae, buccal mucosa and tongue (Fig. 2). White patchy lesions were also noted in both lateral borders the tongue, as well as white removable plaques with erythematous background in the dorsum of the tongue, buccal mucosa, palate, and labial mucosa. Ulcerative lesions were also identified on the esophagus.
In both cases, incisional biopsies of cutaneous and oral lesions were performed. Histological evaluation showed ulcerated fragments containing diffuse chronic granulomatous inflammation located deeply in the connective tissue. Periodic acid Schiff and Grocott-Gomori methenamine-silver stains highlighted round yeast-like fungal structures, which showed spherical, oval, or elongated (cigar-shaped) morphology by exfoliative cytology evaluation (Fig. 3). Yeast culture showed at first, white-creamy membranous colonies which later turned to black-leathery color. Microscopic evaluation of the colonies showed septate hyphae of pyriform conidia with typical "daisy-like" arrangement at the end of the conidiophores (Fig. 3). The microscopic diagnosis was of sporotrichosis in both cases. The correlation between clinical and microscopic findings of both cases lead to the final diagnosis of disseminated sporotrichosis. The second patient was then diagnosed with acquired immunodeficiency syndrome (AIDS) due to CD4 count and viral load associated with deep fungal infection.
The first patient was submitted to amphotericin B treatment for 15 days (1 mg/kg daily), which was subsequently changed to 400 mg of itraconazole, daily, for 2 weeks. As cutaneous lesions persisted, patient was submitted to itraconazole 800mg daily for 6 months. Therapy for tuberculosis followed with ethambutol and isoniazid. Clinical improvement was observed for both cutaneous and oral lesions after 6 months, but the patient did not attend the following appointments. The second patient received 1.5 mg/kg of amphotericin B for 2 weeks, followed by 400 mg of itraconazole, daily, for the next 2 weeks. A good response was observed, with complete remission of cutaneous and oral lesions; the patient missed long-term follow up appointments. | null | Not supported with pagination yet | null |
PMC6585217_01 | Female | 41 | A 41-year-old Asian female patient reported to the Department of Oral and Maxillofacial Surgery with a 4-month history of a gradually increasing swelling on the right side of the face. The swelling was largely painless with no other associated functional symptoms. On local examination, a diffuse swelling was observed measuring about 6 cm x 5 cm on the right side infraorbital region with regional lymphadenitis of the submandibular region of that side. The skin over the swelling appeared normal with no signs of infection or inflammation [Figure 1 (a and b)]. The lump was diffuse, firm, and mildly tender. Fixation to the underlying structures was not present. Intraoral findings were unremarkable with no foci of infection. No other distant lymphadenopathy was elicited clinically. All her hematological investigation parameters were within normal limits. Chest X-ray confirmed the absence of any pathology including hilar lymphadenopathy. The clinical differential diagnosis comprised a wide spectrum of conditions such as lymphoma, fibrosarcoma, and neuroma.
MRI scan of the head and neck showed a homogeneously enhancing infiltrative lesion seen involving the premaxillary space, buccal space, retromolar trigone, and lateral pterygoid in the masticator space on the right side. There was no significant bony destruction. Multiple enhancing solid lymph nodes were seen in the right submandibular, upper deep jugular group and the left submandibular group, largest measuring 18 mm x 12 mm in the right submandibular region. MRI report gave a differential diagnosis of neurofibroma [Figure 2].
FNAC was performed initially, but the result was inconclusive. Therefore, we proceeded with examination under anesthesia and biopsy. The incisional biopsy report suggested a nonspecific type of lymphoid hyperplasia. Hence, definitive surgery was planned with complete excision of the lesion. Intraoperatively, it was observed that the mass was well defined, capsulated, and firm. The histopathology showed dense fibrous connective tissue with some areas exhibiting sheets of numerous small well-differentiated lymphocytes interspersed along with reactive lymphoblasts that were infiltrating into the muscle tissue, blood vessels, and nerves, and in few areas, it formed germinal centers. Mixed type of inflammatory cells including plasma cells and macrophages were seen. The final histopathology report confirmed the diagnosis as reactive lymphoid hyperplasia with no evidence of malignancy.
Additional immunohistochemistry studies were performed to arrive at a more definitive diagnosis. It showed positivity for CD4, CD5, CD3, and CD20 and positivity for both kappa and lambda. This strongly suggested a pathology of inflammatory origin, ruling out malignancy. The patient was kept under close observation.
One year later, the patient reported with a recurrent swelling in relation to the right submandibular region. FNAC was performed again, this time from submandibular region. The cellular smear studies showed sheets of centrocytes, centroblasts, lymphocytes with epithelioid granulomas composed of round-to-oval cells with abundant cytoplasm, and sole-shaped nucleus admixed with necrosis and fibrous tissue suggesting granulomatous lymphadenitis.
In view of the earlier histopathological studies being inconclusive, persistent swelling, and FNAC showing granulomatous changes, we opted for a multidisciplinary approach to rule out other granulomatous diseases such as atypical tuberculosis and sarcoidosis. Fresh CT contrast studies were obtained. CT report suggested a diffusely enhancing soft tissue density lesion in the right buccal region involving upper and lower gingivobuccal space and retromandibular space. The region was closely abutting the right side of the mandible and obliterating the fat plane in the masticator space [Figure 3 (a and b)]. Multiple enlarged lymph nodes were noted in the submandibular region and the upper deep cervical regions, the largest size being 2.1 cm in the submandibular region.
Lymph node biopsy was performed under general anesthesia, through a right submandibular approach. Intraoperatively, two huge solid lymph nodes, well encapsulated and firm in consistency, were removed [Figure 4]. The samples were sent for both histopathological studies and for microbiological tests. The culture test was negative for mycobacterium. The histopathology report this time suggested lymph nodes with multiple predominant follicles with prominent germinal centers with extensive fibrosis and inflammatory cells including multinucleated giant cells. Amidst these proliferating capillaries, prominent endothelial cells were evident. Based on the histopathology report, the patient was evaluated for serum immunoglobulin E (IgE) levels, peripheral eosinophils, and absolute eosinophilic count to rule out Kimura's disease. The IgE levels in this patient were considerably increased with 417 IU (reference value: <180 IU), absolute eosinophil count was marginally elevated with 445/cumm (reference value: <350/cumm), and differential count of eosinophils was 5%. The diagnosis of Kimura's disease was confirmed thereafter.
Based on the available scientific evidence, the immunologist suggested that the patient is started on systemic steroid therapy with a loading dose of 60 mg of prednisolone in divided doses for 3 months. There was good response to steroid therapy, and the lump started to regress within 3 months which was confirmed by CT scan. Steroid dose was tapered to 2.5 mg OD over a period of 6 months. Complete remission of the lesion is observed for the past 18 months, and the patient is on a maintenance dose of 2.5 mg of oral prednisolone. | cervicofacial lymphadenopathy, kimura's disease, immunohistochemistry | Not supported with pagination yet | null |
PMC6479154_01 | Male | 10 | A 10-year-old boy came with ulcer in neck and axilla region. The lesion began as papules that gradually developed into nodules, pustules and painless suppurative ulcer (Fig. 1A). Patient also had chronic cough with yellowish sputum since several months along with low grade fever and weight loss.
Physical examination revealed ulcer with suppurative surface in the bottom part, along with nodule measuring 4 cm x 0.5 cm (Fig. 1A). Around his ear, some crusts were found measuring 3 cm x 0.5 cm typical for scrofuloderma (Fig. 1B). In axillary region, there were also painless ulcers with pustulated sinus and purulent discharge, surrounded by bluish and edematous skin surface (Fig. 1C). There was also mobile and painless lymph node enlargement in the left supraclavicular region measuring 2 x 2 cm.
Chest X ray was within normal limit. Tuberculin skin test was positive with 10mm induration. However, direct smear of sputum specimen was negative for acid fast bacilli. Excisional biopsy of the ulcers was performed and the histopathology result showed epidermal necrosis in the central region surrounded by granulomatous tissue peripherally, forming abscess with histiocytic infiltrate around it, confirming the diagnosis of scrofuloderma.
He underwent CT Scan of the cervical region and multiple lymph node enlargement was found, suggestive for tuberculous lymphadenitis (Fig. 2Aand B). Thus, we did FNAB on the lump and the cytology findings showed groups of epitheloid cell with spindle nucleous with chromatin granules spread equally, surrounded with basophilic amorf mass and fibrous tissue. The background staining of the smear was mature lymphocyte, lymphoblast, neutrophil and macrophage, confirming the diagnosis of tuberculous lymphadenitis (Fig. 2C). He was then diagnosed with scrofuloderma with multiple cervical tuberculous lymphadenitis.
He was treated with standard regimen of anti-tuberculosis drugs containing Rifampicin (R), Isoniazid (H), Pyrazinamid (Z), and Ethambutol (E) for 2 months continued by Rifampicin (R), Isoniazid (H) for the next 4 months. In the fourth months, the lymph node enlargement in the cervical region were shrinked (Fig. 3A and B). The ulcers in the neck and axilla began to resolve gradually leaving scar tissue (Fig. 3C). In some spots, some crusts were still found. Overall, he showed a satisfying response to the anti-tuberculosis therapy. | cutaneous tuberculosis, lymphadenitis, scrofuloderma | Not supported with pagination yet | null |
PMC8062804_01 | Male | 2 | A 2-year-old male castrated domestic shorthair cat was presented to his veterinarian for suspect urethral obstruction. On presentation, he was documented to have a BCS of 3 on a 5-point scale, weighing 4.85 kg. A full, hard bladder was palpated, and white, gritty material was noted at the tip of his penis. Pre-anesthetic bloodwork revealed few abnormalities (see Table 1). A catheter was passed with some resistance, allowing emptying of the bladder. Copious amounts of "sand" were present in the urine. Urine pH was 8.0, cocci bacteria and large quantities of struvite crystals were detected (Table 2). Due to the presence of struvite crystals in the urine and small uroliths visualized by ultrasound, a canned feline veterinary therapeutic diet formulated for dissolution and prevention of struvite uroliths was recommended (Table 3). Previously, the cat had been fed commercial plant-based diets (Table 3). The cat was discharged with amoxicillin-clavulanic acid (62.5 mg Q12h PO, 10 days), prazosin (0.5 mg Q12h PO, 15 days, then 0.5 mg Q24h, 15 days), buprenorphine (0.08 mg Q8h PO, 16 days, tapering to 0.04 mg Q24h as required), and robenacoxib (6 mg PO SID, 6 days). Alprazolam (0.5 mg Q12h, 14 days) was also prescribed for underlying anxiety. The cat re-presented twice over the following 5 weeks with acute difficulty urinating, vocalizing, straining, and urinating outside of the litter box. No abnormalities were detected on physical examinations and urinalyses revealed improvement in urine acidity with fewer struvite crystals. Against recommendations, the client discontinued the therapeutic food as it contained animal products, and the cat was returned to his previous commercial plant-based diet.
One month later, the cat was referred to the Ontario Veterinary College Health Sciences Centre Clinical Nutrition Service for consultation regarding plant-based dietary management for FLUTD. The owner was vegan and required that they feed the cat a plant-based diet in order to comply with their ethics. On presentation, the cat had a BCS of 5/9, weighing 5.0 kg. Nutritional evaluation revealed risk factors based on the WSAVA Nutritional Evaluation Checklist, including living in a multi-cat house, ongoing urinary signs, and being fed an unconventional diet. The cat's resting energy requirement (RER) was estimated using: (BW0.75*70 kcal) = 250 kcal. Given the cat's activity, current bodyweight and BCS, his daily energy intake was estimated to be RER*1.2 = 300 kcal. A recommendation was made for a commercial feline veterinary therapeutic diet formulated to manage signs of FLUTD (Table 3), which was declined by the client as it contained animal products. After discussing the challenges related to management with a plant-based diet, commercial plant-based diets were identified as alternative strategies. While detailed nutrient profiles are not typically available for many commercial plant-based diets available in Canada, nutrient analyses had been performed as part of a research project conducted by the authors. Diets meeting the AAFCO adult maintenance recommendations with the lowest concentration of struvite precursors were identified (Table 3). Based on energy density, food doses were recommended to combine kibble and canned food in a 50:50 ratio. The recommendation was made for the cat to be fed 35 g (143 kcal) kibble and 150 g (148 kcal) canned food, allowing for 10 kcal (3% of daily energy intake) to be given as treats or snacks. The client was advised on the energy and nutrient content of suitable treats and snacks. Recommendations were made to encourage water intake, feed small, frequent meals, and to supplement the diet with eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) at a dose equivalent to 0.5% of the diet on a dry matter basis. Recommendations to increase water intake included adding water to food, adding palatants to water, providing multiple water dishes in different locations, different materials (e.g., ceramic or metal), offering wide dishes to avoid whisker stimulation, and drinking fountains.
Three months later, the cat re-presented to his veterinarian for inappetence and weight loss. His bodyweight was recorded at 4.30 kg, though BCS was still documented as 3 on a 5-point scale. According to dietary anamnesis the cat would not eat the canned diet, nor accept soaked kibble or the DHA+EPA supplement recommended by the Clinical Nutrition Service, and he had continued to be fed the commercial plant-based diet he had been fed prior to the urethral obstruction (Table 3). Urine was collected by the client using non-absorbent litter (Table 2). A veterinary therapeutic dissolution diet was again discussed with the client as being the most evidence-based solution to mitigate risk of recurrent FLUTD signs, but the client declined this recommendation. Mirtazapine (2 mg Q24-48h as required) was prescribed to stimulate food intake. Though no dietary change was implemented, recheck examination 3 weeks later revealed a slight increase in body weight from 4.30 to 4.43 kg. Four months later, the cat re-presented for decreased urine output. At that time his body weight was 4.51 kg and his BCS was documented as 5 on a 9-point scale. Free-flow urine was examined again (Table 2), and a feline veterinary therapeutic dissolution diet was recommended, but again declined. The client elected to try to increase water intake and began preparing a home-cooked plant-based diet (Table 4).
Three months later, the cat was re-presented to the Clinical Nutrition service for management of inappetence. Despite the client's concerns about the cat's intake, on presentation the cat weighed 5.8 kg with a BCS of 6 on a 9-point scale, his heaviest recorded weight. Evaluation of the home-cooked plant-based diet using diet formulation software (Balance IT ) revealed the diet to be deficient in numerous nutrients, most notably meeting 0% of the cat's arachidonic acid requirement, while it provided iodine over 8 times the maximum recommended dose (Table 3). On a daily basis, the cat was fed: 1 tbsp homemade food, 2 tbsp of vegetables (pumpkin, green lentils, peas, squash, green beans, or corn), 3/4 cup of kibble B, 1/8 tsp enzyme supplement, 250 mg methionine, and 1/8 tsp psyllium. The diet recipe was reported to have been acquired from a friend and it was unknown where the dosing had been acquired for the supplementation of enzymes, methionine, or psyllium. Treats included commercial plant-based deli slices, non-dairy cheese, potato chips, coconut yogurt, non-dairy sour cream, and dried nori seaweed. The client was made aware that the cat was slightly overweight and that his estimated daily caloric intake was more than sufficient to maintain his current bodyweight. Concern for inappetence or inadequate intake was not necessary. As the cat would not eat a canned food or soaked kibble, it was suggested to combine the kibble with preferred plant-based treats and foods the cat would eat, while also increasing water intake. The client was advised not to feed more than 10% of the daily caloric allotment from foods other than the kibble. Additionally, the methionine dose was increased from 250 to 500 mg to acidify the urine.
One month later, the cat was eating the recommended food, but struvite crystalluria persisted and the owner was concerned about inability to increase water intake on the dry extruded diet. The cat was re-presented to the Clinical Nutrition Service, weighing 5.8 kg with a BCS of 6 on a 9-point scale. A homemade plant-based diet was designed using web-based formulation software1 (Tables 3, 4) to meet the AAFCO nutrient profile for adult maintenance with low concentrations of struvite precursors, and utilized ingredients intended to promote urine acidity. Acidification of the urine was predicted by calculation of the base excess of the diet. Base excess in the food was calculated using the equation: Base excess (mmol/kg DM) = 2[Ca]+2[Mg]+[Na]+[K]-2[P]-2[Met]-[Cl]. Plant-based fatty acid supplementation was recommended, with plant-based arachidonic acid and EPA+DHA. As the cat was slightly overweight, a conservative energy intake was recommended to just meet his RER of 250 kcal to prevent further weight gain. The next urinalysis performed revealed a stable USG and pH, though struvite crystals were absent. The client was encouraged to continue regular rechecks with their family veterinarian, and feedback from the client 9 months later revealed the cat was doing well, he continued to eat a combination of the homemade food and commercial plant-based kibble, his urine was consistently free of struvite crystals, pH maintained between 6.5-7.0, and the USG below 1.040. The owner reported no further concerns with inappetence, no changes in bodyweight, and the cat had suffered no further FLUTD episodes. | crystalluria, feline nutrition, struvite, urethral obstruction, vegan | Not supported with pagination yet | null |
PMC4821331_01 | Male | 49 | A 49-year-old man was referred to our hospital with progressively worsening shortness of breath, dry cough and weight loss of approximately 10 kg. Three weeks prior to admission, the patient had presented to another hospital and was treated with antibiotics without improvement.
His past medical history was remarkable for tobacco addiction and alcohol abuse. He also had used cocaine up to 2 years before presentation. He did not report having any kind of environmental exposures or pets.
On admission, his blood pressure was 140/80 mmHg. His temperature was 38 C, and auscultation of his chest revealed diminished breath sounds and wheezing. The oxygen saturation (SpO2) was 98% on room air.
Notable laboratory findings included the following: a white blood cell count of 13,000/mL, a platelet count of 439,000/mL, and a hemoglobin of 16.7 g/dL. HIV serology, antinuclear antibody (ANA) and anti-neutrophil cytoplasmic antibody (ANCA) were negative. The prostate-specific antigen (PSA) level was lower than 4.0 ng/mL.
Pulmonary function tests revealed a severe non-obstructive defect, and a chest CT scan showed multiple lung cysts that predominated in the lower lobes (Fig. 1). A bronchoscopy was performed, and no endoluminal or mucosal lesions were observed. A bronchoalveolar lavage (BAL) culture was negative for bacterial infection, Mycobacterium tuberculosis (and nontuberculous mycobacteria) infection and fungal infection. The cytological examination did not find atypia, and CD1a immunostaining of the BAL cells was also negative.
The patient was treated with intravenous broad spectrum antibiotics and steroids for 14 days, showing moderate improvement of his respiratory symptoms. He was discharged from the hospital and readmitted three weeks later with dyspnea and productive cough with purulent sputum.
He was alert, tachycardic and tachypneic. Chest auscultation revealed diminished breath sounds and bilateral wheezing. The SpO2 was 85% on room air.
Laboratory findings included the following: a white blood cell count of 41,500/mL, a blood glucose of 331 mg/dL, and a C reactive protein (CRP) level of 13.9 mg/dL.
A new chest CT scan demonstrated an increased number of cysts (some of which were filled with mucus), bilateral ground glass opacities and consolidation.
A diagnosis of nosocomial pneumonia was made. The patient was started on antibiotic therapy with vancomycin and piperacillin-tazobactam, but his clinical condition deteriorated rapidly. He was intubated and mechanically ventilated. A second bronchoscopy was performed, and transbronchial biopsies were obtained.
The biopsy specimen revealed a small fragment of lung parenchyma infiltrated by large cells, some of which had prominent nucleoli and eosinophilic cytoplasm, showing gland formation areas and focal necrosis. The tumor cells were CK-20-positive, villin-positive, CK7-negative and TTF1-negative. The patient was diagnosed with metastatic colorectal cancer.
The patient died on the 4th day after admission. | adenocarcinoma, colorectal cancer, cystic lung disease, lung metastasis | High resolution CT showing multiple cysts, which markedly vary in size, in the lower lobes and nodules that tend to cavitation. |
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PMC10402786_01 | Male | 43 | A 43-year-old man was admitted to the Clinica de las Americas (CDLA) in Santa Cruz de la Sierra, Bolivia, presenting with moderate-intensity, continuous crushing chest pain radiating to the lower jaw and the left shoulder. The pain had started two days prior and had progressively increased in intensity.
Five days prior to his hospitalization, the patient had presented to the emergency department for fever, headache, retro-orbital pain, general body aches, and joint pain. Due to the high degree of suspicion and multiple cases of dengue in the community, a dengue test (ELISA IgM) was performed, yielding a positive result, which was subsequently confirmed through reverse transcriptase polymerase chain reaction (RT-PCR). The patient was hemodynamically stable with no signs of heart failure, exhibiting no murmurs or rubs on auscultation, and a chest-radiography performed at that time showed normal results.
The patient's electrocardiogram (EKG) revealed sinus rhythm with a heart rate of 95 beats per minute. Additionally, an ST segment elevation of 2 mm was observed in leads II, III, aVF, and V4 to V6 (Figure 1). This was interpreted as acute coronary syndrome with ST-segment elevation, so blood tests (including cardiac biomarkers) were requested and the myocardial infarction protocol (primary angioplasty) was activated. However, a coronary angiography revealed no significant lesions.
Simultaneously, a transthoracic echocardiogram was performed, revealing normal systolic function in both ventricles. The left ventricular ejection fraction (LVEF), assessed using Simpson's method, was 66%, and the diastolic function was preserved. Longitudinal deformation was -19.8% with a minor decrease in the deformation affecting the basal and medial inferoseptal segment. Finally, the parietal pericardium was found enlarged and diffusely hyperechogenic, suggesting an inflammatory process at that level (Figure 2).
Complete blood count and basic metabolic panel lab results all yielded normal results, with hemoglobin of 12.6 g/dl, hematocrit of 39.2%, leukocyte count of 8700 cells/mul with normal differential and a platelet count of 263,000/mul. Creatinine, sodium and potassium levels were 0.7 mg/dl, 142 mEq/L, and 4.6 mEq/L, respectively. Cardiac markers were slightly elevated, with a NT-proB-type Natriuretic Peptide (NT-proBNP) level of 678 pg/mL (normal value <125 pg/ml), a troponin T level of 154 ng/L (normal value <14), but with a normal creatine phosphokinase (CPK) value of 88 U/L (normal value <308 U/L).
Cardiac magnetic resonance imaging (MRI) with gadolinium revealed normal-sized cardiac chambers, preserved right ventricular function, and a LVEF of 52% (lower than the normal range) in a context of mild hypokinesia of the inferior wall of the left ventricle (basal and medial segments) (Figure 3).
The presence of myocardial edema was also observed in the same inferior wall with inferoseptal extension (Figure 4). Late enhancement sequences revealed gadolinium uptake in the basal, medial, and inferior basal inferoseptal segments of the left ventricle, and the pericardium in its basal region (Figure 5). All of these findings are consistent with acute myocarditis.
The differential diagnosis also included a number of pathologies characterized by chest pain, such as acute coronary syndromes, aortic dissection, pulmonary embolism, pneumonia, pneumonitis, tuberculosis, viral myocarditis, musculoskeletal disorders, gastric ulcer, gastroesophageal reflux disease, pneumothorax, herpes zoster, depression, and panic disorder.
Considering the exclusion of acute myocardial infarction through normal coronary angiography, the clinical findings, elevated cardiac biomarkers, positive specific serology, suggestive cardiac images, and the epidemiological context, a dengue myocarditis diagnosis was suggested.
The patient was treated with nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and colchicine, resulting in clinical improvement of pain and reduction in cardiac biomarkers levels. During the first 24 hours of admission, the patient had persistent hiccups, which were effectively managed with intravenous metoclopramide. Discharge was effective on the third day of admission with prescriptions for acetylsalicylic acid (750 mg every eight hours for one week) and colchicine (0.5 mg daily for two weeks). | acute myocarditis, dengue, expanded dengue syndrome | Not supported with pagination yet | null |
PMC6132374_01 | Female | 10 | Mia is a 10-year-old African American female living with a family member in an urban area. Mia is diagnosed with PTSD due to abuse and neglect experienced while living with a foster family. Mia was born addicted to substances and consequently taken into custody by the Department of Children and Families (DCF) and placed with a foster family who fled to another state. During this period, Mia was subject to extensive abuse and neglect by her foster parents, including severe sexual abuse. Mia was subsequently brought back to the area in which she was born, and placed with a family member with whom she currently lives. Mia presents with sexualized behaviors which she has acted out towards family members and the family dog. She also has a history of isolated incidents during which she plays with her feces.
Mia is an intelligent and bubbly girl that can present with a high rate of distractibility and impulsivity. Mia demonstrates oppositional behaviors when teachers or providers attempt to redirect her, but she is often able to reflect on/has insight around her actions. Mia has been receptive to trauma-informed interventions, which is why she was initially referred for equine therapy. Mia is motivated by working with animals and gravitates towards "hands on" activities.
Before the start of EFT-CT, Mia was highly symptomatic across a range of clinical domains. On the CBCL, her primary caregiver indicated that Mia exhibited a number of behavior problems on the (CBCL Total Problems T-score = 68, clinical range) both internalizing and externalizing in nature, including clinically significant social problems (T = 72), thought problems (T = 74), and attention problems (T = 77). Her caregiver also reported broadly impaired executive functioning on the BRIEF-P, indicated by a Global Executive Composite score in the clinically significant range (T = 71, 98th percentile), and with the most significant problems in the domain of metacognition (T = 75, 98th percentile, clinically significant range). In addition to significant difficulty with getting started on tasks, organizing her thinking, or strategizing, self-monitoring and working memory, Mia exhibited significant difficulties with behavioral inhibition (T = 78, 98th percentile). Regarding trauma-specific symptomatology, Mia endorsed clinically significant problems in two of the three symptom DSM-IV-TR symptoms clusters on the PTSD-RI (avoidance, T = 80; arousal, T = 92), as well as subclinical problems with trauma-related intrusions (T = 63), and a posttraumatic stress total score also in the clinically significant range (T = 86). She also endorsed clinically significant problems with dissociation (T = 75), and sexual concerns (T = 99), related to Mia's trauma exposure. Mia herself did not endorse any significant symptoms on a self-report of depression (CDI-2 total problems T-score = 54; 66th percentile).
Mia was able to form a strong and positive attachment with the therapy pony during EFT-CT sessions. Because of her motivation to work closely with the pony, she successfully followed instruction and safety protocols. Much of the work with Mia at Bear Spot Farm focused on riding and helping her gain an understanding and awareness of her body. For instance, her clinician carried out rhythm and balance-based exercises with Mia while she rode, to help her gain an effective riding position, and thus communicate with therapy pony better. These exercises set the stage for Mia to be in her optimal window of arousal, evidenced by her decreased impulsivity and heightened sense of control over her body. Mia demonstrated improved functioning and was able to express feeling "free" and "calm" while she rode.
Due to difficulties with transportation and scheduling, Mia was unable to continue her participation in the pilot program. While she continued to receive other services, Mia demonstrated setbacks after exiting the pilot program. Increased impulsivity and oppositional and unsafe behaviors have created challenges for Mia and her family across multiple domains. After treatment, Mia also played with and hid her feces on a few occasions. Mia did not complete enough treatment to reach a second clinical assessment period, thus, no data on her clinical functioning post-treatment is available. | animal assisted therapy, child traumatic stress, complex trauma, equine therapy, trauma, treatment | Not supported with pagination yet | null |
PMC4897012_01 | Male | 79 | A 79-year-old male presented to his primary care physician with the chief complaint of an enlarging lump on his chest. He first noticed it 2-3 days prior to presentation, and thought it had increased in size over that time. He had no pain, fevers, chills, or malaise.
The patient's past medical history was significant for tuberculosis which was treated with left pneumonectomy and thoracoplasty in 1950. He had oxygen dependent chronic obstructive pulmonary disease.
On physical examination, he had an erythematous lump on his left anterolateral chest wall. It was fluctuant and mildly tender. His temperature was 99.2 degrees Farinheit.
Needle aspiration of the lump yielded pus. An incision and drainage was performed, which revealed copious pus and a large abscess cavity, estimated to measure approximately 15 x 7 cm. On exploration and palpation of the wound, there was concern for communication with the pleural space.
A chest radiograph was obtained (Fig. 1). This demonstrated truncation and deformation of the upper left ribs with collapse of the chest wall and volume loss of the left hemithorax. The left hemithorax was nearly completely opacified and plaque like calcifications were present along the chest wall. A small amount of air was present.
Subsequently, computed tomography of the chest was performed (Fig. 2). This demonstrated absence of most of the left first through 7th ribs and distortion and collapse of the left upper thorax. The upper chest wall was apposed to the superior mediastinum. The hemithorax was peripherally calcified and filled with fluid and several air-fluid levels. Lobular areas of high attenuation tissue were contiguous with the chest wall, mediastinum and diaphragmatic surfaces. The subcutaneous abscess cavity was filled with air and fluid.
Intraoperative bronchoscopy revealed a normal right bronchus and intact left bronchial stump without evidence of bronchopleural fistula. A left thoracotomy incision was made and 2 left ribs were resected. The pleural space was filled with 400cc of pus, white necrotic material, and lobules of granular, clay-like yellow material. Following extraction of this material, an Eloesser flap was created by sewing the skin to the parietal pleura, creating a 4 x 10cm opening for pleural drainage. The patient tolerated the surgery well. 2+ Acid fast bacilli were present on AFB stain of the pleural fluid. Appropriate anti-tuberculous therapy was initiated. | ct, computed tomography, tb, tuberculosis | Not supported with pagination yet | null |
PMC5401737_01 | Male | 64 | A 64-year-old man presented to the tertiary referral hospital with a 1-month history of severe otalgia, constant otorrhea, and a 1-week history of facial weakness on the left side. He also complained of painful mastication on the same side. He had no previous history of ear infection, diabetes mellitus, or tuberculosis. The patient had a history of excessive alcohol consumption.
At arrival, his temperature was 37.2 C. A blood test revealed leukocytosis (12.3 x 109/L) and normal glucose level. On physical examination, the patient had a facial paralysis grade IV according to the House-Brackmann scale. Otoscopically, there was edema with granulation tissue in the EAC and an eardrum perforation in lower quadrants on the left side. Pus and granulations were also detected in the tympanic cavity on that side.
Radiologically, mastoiditis was diagnosed (Figure 1(a)). CT scans also showed erosion of the anterior-inferior walls of the middle ear cavity and external auditory canal (Figure 1(b)). Air bubbles in the prestyloid compartment and TMJ were also detected.
From the geniculate ganglion to the stylomastoid foramen, no obvious facial nerve bony canal destruction was detected. Multiple biopsies showed highly vascularized granulation tissue with leukocytic infiltration and foci of necrosis. They did not reveal any neoplasm or granulomatous inflammation. A culture showed a growth of alpha-hemolytic Streptococci.
Treatment with intravenous antibiotics (Cefuroxime 750 mg three times daily, Metronidazole 500 mg twice daily, and Ciprofloxacin 200 mg twice daily), aural suction, and topical Ciprofloxacin and Dexamethasone drops was started immediately. However, conservative management and intensive aural toilet were ineffective, and the patient underwent surgery. Canal wall down mastoidectomy was performed. Removal of the incus was required to reestablish the patency of the blocked aditus ad antrum and attic. A dehiscent facial nerve in the tympanic portion was observed intraoperatively. Ossiculoplasty with repositioning of the incus was performed at the same procedure. However, after a short improvement, purulent otorrhea and pain in the preauricular pain reoccurred. New massive granulations in the anterior part of the tympanic cavity were observed. Pus in the canal appeared with closure of the mouth and clenching. Repeated CT scan of the temporal bones and temporomandibular joint (TMJ) revealed a bony sequestrum and defect in the anterior middle ear cavity and external auditory canal walls (Figure 2(a)). MRI with intravenous contrast was carried out; in the left infratemporal fossa, an abscess (30 x 9 mm) enhanced on the periphery with the irregular contours was detected (Figure 2(b)). The abscess extended from the external auditory canal towards the jugular fossa, carotid, and parapharyngeal compartments. Debris in the mastoid on the left was described as well. Altered intensity of the lateral pterygoid muscle on the left as well as thrombosed internal jugular vein and partially thrombosed transversal and sigmoid sinuses were detected on the left (Figures 2(b) and 2(c)).
A final clinical diagnosis of temporal bone osteomyelitis complicated by infratemporal abscess coexisting with mastoiditis and necrotizing external otitis was made on the basis of medical signs and imaging data. The second operation was carried out in collaboration with a neurosurgeon (S. R.). Lateral petrosectomy was performed, and a drain was inserted into the abscess cavity (Figure 3(a)). Granulations were removed from the middle ear cavity. A defect in the anterior wall was identified (Figure 3(b)). The tympanic part of the temporal bone was drilled out, and a large sequestrum was removed (Figure 3(c)). Next, tympanoplasty type III using temporal muscle fascia was performed (Figure 3(d)).
The patient continued to use Ciprofloxacin 500 mg twice a day for six weeks after surgery. On follow-up, six months postoperatively, the tympanic membrane was intact, and the mastoid bowl was noncompletely epithelized (Figure 4).
Grade V House-Brackmann facial paresis persisted at the last follow-up. | null | Not supported with pagination yet | null |
PMC5401737_03 | Male | 93 | A 93-year-old man presented to the emergency department of our hospital with a 1.5-month history of severe otalgia and constant otorrhea on the right side. He had no previous history of otologic diseases, DM, or lung tuberculosis. Otoscopically, the bony part of the EAC was partly obstructed by massive fleshy granulations. Granulations were also observed in the tympanic cavity through the eardrum perforation. A blood test showed leukocytosis (18.2 x 109/L). S. aureus was isolated from the ear swab.
CT scan revealed an osteolytic lesion of the petrous apex of the temporal bone with loss of clear bony margins of the carotid foramen (Figure 7(a)). Radiologically destructive peritubal mastoiditis was diagnosed. Several bony sequestra were clearly seen on the CT scans. In this case, an infection extended directly through the defect in the anterior wall of the tympanic cavity into the surrounding spaces: mandibular fossa and temporomandibular joint (Figures 7(b) and 7(c)). Diffuse pericapsular inflammation of the latter with widened joint cavity was seen on the CT scans.
Clinically, a diagnosis of coalescent mastoiditis complicated by temporal bone osteomyelitis coexisting with necrotizing external otitis was made.
Due to the age and anesthetic risk, a conservative tactic was chosen with active removal of the granulations under local anesthesia. After the treatment, subjective improvement of otalgia and reduction of the granulations were observed. The patient was discharged from the hospital after one week. Long-term antibiotics (Cefuroxime 500 mg twice a day for four weeks) with local drops were prescribed according to the culture results. | null | Not supported with pagination yet | null |
PMC7196993_01 | Female | 61 | A 61-year-old female with past medical history of multiple myeloma diagnosed July 2017 (stem cell transplant through Mayo Clinic Dec 2017 and chemotherapy instituted April 2018), type 2 non-insulin dependent DM (diagnosed Dec 2017 with last A1C of 11.2%- March 2019), unprovoked DVT in 2018 (Eliquis), and hypertension, who presented to the ER March 2019 with 2 day history of progressive weakness and decreased appetite. On day of admission, she was unwilling to get out of bed due to weakness, and her significant other noted right facial droop and right upper lid lag. In the emergency department, the patient reported blurred vision and headache for 3 weeks. She also reported no recent fever, vomiting, head injury, syncope, upper respiratory infection, abdominal pain, or urinary symptoms. With questioning, there had been no recent travel. The patient had suffered intermittent diarrhea that started after she was prescribed metformin. The patient was seen by her primary oncologist the day before, and serum testing was found to be baseline. She was compliant with her medications including metformin, Revlimid (lenalidomide), acyclovir, and Eliquis.
There was decreased attenuation throughout the white matter of the right cerebral hemisphere. This was asymmetric compared to the left. There was mild mass effect on the right lateral ventricle. Findings were worrisome for diffuse vasogenic edema. Differential would include sequela of prior therapy, underlying mass, less likely, given the asymmetry, and demyelinating process
Focal area with decreased attenuation in the right basal ganglia. Findings may represent a small lacunar infarction.
Mild diffuse cerebral volume loss.
CT scan head per radiologist:
MRI interpretation by radiologist (Figure 1): Extensive patchy right frontoparietal and central midbrain perivascular (likely perivenular) enhancement. There is associated asymmetric white matter edema and midbrain edema. Differential considerations include vasculitis, intravascular lymphoma, amyloid angiopathy, granulomatous angiitis, and less likely demyelinating process. A small irregular area of restricted effusion in the right parietal lobe is nonspecific. Intravascular thrombus and venous infarction cannot be excluded.
The patient remained stable in the ER and was admitted to medical bed with close neurologic monitoring. Revlimid, metformin, and Eliquis were held. We continued prophylactic acyclovir.
Neurosurgery as well as Oncology was consulted with continued daily oversight by Neurology.
Day 1: patient stable with similar exam findings.
CSF analysis including flow cytometry: no malignant cells and cytology, and no monoclonal process.
CSF fluid analysis: 83 lymphs, 11 monocytes, and 6 neutrophils.
CSF cell count (2 bottles): RBCs 161/146 muL; nucleated cells 32/20 muL; neutrophils 2/6%, lymphs 80/83%, and monocytes 17/11%.
Glucose 62 mg/dL and protein 69 mg/dL. Blood glucose was 95 at the time of the LP.
CSF: complement factor elevated at 233, complement C3 elevated at 200, and complement C4 elevated at 48.
CSF immunoglobulin testing unremarkable.
CSF DNA testing: ACE, cryptococcus, E. coli, Epstein-Barr, herpes simplex, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumococcus, GBS, CMV, Lyme, West Nile, neuron-specific enolase, VDRL, human herpes, varicella-zoster, human parechovirus, H. influenza: all negative.
Day 1: lumbar puncture results.
JC virus and prion testing pending and not resulted until 1 week later but ultimately negative.
Specific autoimmune and connective tissue disorder testing negative.
Hepatitis C&B, HIV, and syphilis testing negative.
Initial CSF culture negative for growth after 6 days
CT chest abdomen and pelvis on day 1: slight interval enlargement of left adrenal mass (present on previous imaging); otherwise no evidence of acute/new disease process.
CTA head and neck on day 1: redemonstrated low attenuation diffuse right cerebral edema with possible small site of hemorrhage in the right frontal lobe. No vascular abnormality noted.
Blood cultures obtained on day 1 to cover for rare bacterial pathogens were negative after 6 days
Day 2: Neurologic symptoms worsened with facial droop and right eye ptosis, and occlusion of vision. The patient reported increased weakness with limited use of the right arm for ADLs. The patient denied worsening headache, fever, or vomiting. Serum testing on this day revealed negative leukocytosis, however, ESR 37 and CRP 5.11.
Informal consultation completed with radiologist regarding a revisit on the differential diagnosis.
CSF cultures were still negative and given her negative CSF PCR testing for pathogens, and dexamethasone was initiated for cerebral edema and presumed cerebral vasculitis.
On the evening of day 2, the patient reported improvement of clinical symptoms with less ptosis and more strength.
Day 3: the patient with continual clinical improvement and requested discharge home in lieu of brain biopsy; however, this request was denied.
CT imaging unchanged and the patient afebrile.
The patient was scheduled for brain biopsy on Day 4 but was cancelled and rescheduled for Day 7 due to pending prion testing and lack of neurosurgical equipment backup while awaiting prion results. A further investigation regarding etiology of cerebritis was not further evaluated, given clinical improvement and stable vitals.
Day 6 in the AM: the patient's condition deteriorates with vomiting and escalating hypertension and tachycardia. Facial drooping on the right returned. The patient was afebrile in the AM on morning rounds with WBC 3.8, normal electrolytes, and unchanged renal function with glucose 230 and calcium 8.5. The patient was immediately transferred to ICU, and repeat imaging was ordered: CT head revealed no significant interval change in the cerebral white matter hypodensity with a small dense focus within the right frontal lobe similar to prior CT exam.
MRI head on day 6: Little change in abnormal brain MRI with diffuse parenchymal and perivascular enhancement in the right frontal lobe, right occipital lobe, floor of the 4th ventricle, and interpeduncular cistern. Minimal decrease in vasogenic edema. Small amounts of petechial blood products. Continue mild effacement of the right lateral ventricle and minimal right to left shift of midline. Differential: multifocal leukoencephalopathy, lymphoma, encephalitis, vasculitis, or myelomaotsis
The patient was transferred to a Level 1 center early afternoon on day 6, but developed a low grade fever before departure. Before transfer, she was fatigued but responsive. On arrival to the Level 1 center (2 hr away), she was unresponsive with 103F fever. Blood cultures obtained upon arrival and the patient started on prophylactic cefipime, vancomycin, azithromycin, acyclovir, and voriconazole.
Respiratory PCR panel including influenza negative
Toxoplasma antibodies negative
Coccidioides testing negative
HIV, TB, and mycoplasma testing negative
Procalcitonin: 0.04
CT head: continued vasogenic edema right frontalparietal distribution.
CTA head and neck perfusion: unremarkable
Day 6 at Level 1 center:
Day 7: another lumbar puncture completed; however, brain biopsy was held in lieu of ID workup.
CSF results from day 7: 172 nucleated cell, 45% neutrophils, 17% lymphocytes, and 38% macrophages.
Glucose 49 and protein 124; lactate 7.7 and LD 54. Blastomyces, toxoplasma, and varicella negative. Histoplasma and CMV negative.
CSF culture negative for growth at 5 days at the Level 1 center.
Day 7: blood culture positive for Gram-positive rods. Added amphotericin to treatment.
Day 8: ampicillin added to antimicrobial treatment.
Day 11: blood cultures positive for Listeria.
Day 13: gentamicin added to treatment.
Day 15: MRI imaging showed advancement of disease and comfort care instituted.
The patient expired on day 17.
Brain autopsy: revealed abscesses of the white matter in the frontal, temporal, and occipital lobes as well as the midbrain, pons, and cerebellum with multiple macroscopic leukocytes with perivascular inflammation consisting of lymphocytes and plasma cells consistent with listeriosis.
Diagnosis: Listeria cerebritis with bacteremia.
Neurosurgeon agreeable to brain biopsy if CSF analysis inconclusive since the concern was that her imaging finding suggestive of vasculitis or malignancy. | null | Not supported with pagination yet | null |
PMC8569588_01 | Female | 7 | A 7 year old girl presented with a 2 week history of a persistent dry cough, nasal congestion and mild rhinorrhea that progressed to acute onset left-sided chest pain and difficulty in breathing with a low-grade fever. She had no present or past history of wheeze, no easy fatigability or dyspnea on exertion, no body or feet swelling. No history of close contact with a patient known to have tuberculosis (TB) or severe acute respiratory syndrome coronavirus 2 disease (COVID-19) no loss of weight or poor growth, no loss of appetite nor night sweats reported. There was no known history of chest trauma.
At the onset of her symptoms she was initially managed at home as nasopharyngitis with a cough syrup with no resolution of symptoms. She was reviewed in the outpatient clinic with a diagnosis of pneumonia a few days later and standard antibiotics were prescribed. 3 days later she was reviewed by the paediatrician due to the persistent cough and difficulty in breathing. Inhaled salbutamol and oral montelukast were added as treatment for possible asthma. A further 3 days later she developed chest pain that necessitated an admission.
The birth and developmental history were unremarkable. She had no previous admission but had allergy symptoms since infancy which included eczema, history of skin eruptions with ingestion of animal proteins and allergic rhinitis with upper airway obstruction symptoms.
Her clinical examination on admission; temperature of 37.5 C, blood pressure (BP) 98/53(mean BP 63), heart rate (HR) 105, oxygen saturation (SPO2) 93% on room air and increased respiratory rate of 33 breaths per minute.
The respiratory examination revealed tracheal shift to the left side, dullness on percussion and reduced air entry on the left lung zone all indicating left lung collapse (Fig. 1). Systemic examination was positive for orbital shiners, enlarged inferior turbinates and lingual tonsils hypertrophy, dental carries and lastly mild eczema patches on her trunk.
Initial blood gas analysis done showed compensatory respiratory alkalosis and hypoxia: (pH) 7.426, partial pressure of carbon dioxide (PCO2)25.4 mmHg, partial pressure of oxygen (PO2)55 mmHg, base excess (BE)-8mmol/L, serum bicarbonate (HCO3)16.7mmol/L, total carbon dioxide (TCO2)17 mmHg, oxygen saturation (SPO2)90% and lactate 0.65mmol/L. Normal values for Abbott blood gas analysis machine i-STAT CG8+: pH (7.35-7.45), PaO2 (80-105 mmHg), PaCO2 (35-45 mmHg), BE (-2 to +3 mmol/L), HCO3 (22-26 mmol/L), TCO2 (23-27 mmHg), SPO2 (95-98%), lactate 0.36-1.25mmol/L.
The patient was admitted to the high dependency unit (HDU) due to features of compensated respiratory failure for monitoring, oxygen supplementation, intravenous fluids and intravenous antibiotics.
A working diagnosis of features of lung collapse/consolidation, pneumonia and possible foreign body aspiration.
Initial investigations were as follows: Haemogram and serum biochemistry were normal, the inflammatory/infective markers C-reactive protein (CRP) and Pro-calcitonin (PCT) were low and blood culture was negative. Multiplex respiratory panel polymerase chain reaction test (PCR) was negative for viruses and atypical bacteria tested, tuberculosis microbiology and PCR was also negative. COVID-19 test was also negative. Vitamin D levels were low at 22.9 (30-100) U/L.
Based on her clinical and laboratory findings, an additional diagnosis of; upper airway obstruction, due to adenotonsillar hypertrophy, dental carries, eczema and Vitamin D deficiency was made. She was started on intravenous ceftriaxone and flucloxacillin, skin emollients and Vitamin D supplementation. By the second day she had increased work of breathing and was started on continuous positive airway pressure (CPAP) non-invasive ventilation by mask alternating with a non-rebreather high flow oxygen mask (NRM).
A multidisciplinary consult was sought that included the ear, nose and throat specialist (ENT), pulmonologist and the cardiothoracic surgeon. A plan was made for a computerized tomography (CT) scan of the chest, upper airway endoscopy and bronchoscopy with a possible open surgical approach if needed (Fig. 2).
Rigid bronchoscopy was done on day 3 of admission and removal of a small fat like consistency foreign body from the left main bronchus. It was noted that there was minimal mucus in the trachea and no features of major lower airway inflammation of the visualized segment. Grade 3 fibrotic tonsils and enlarged adenoids were confirmed.
Further history revealed that she had choked on chewing gum 2 months prior to presentation but had not experienced any significant respiratory symptoms warranting a review.
She was maintained on oxygen supplementation by NRM on that day, which was being weaned off gradually as tolerated and remained clinically and vitally stable.
By the second day post-bronchoscopy, we managed to wean off oxygen to 1Litre/min via nasal prongs with no respiratory distress. However, there was still minimal air entry on the left upper and mid lung zones. A repeat CXR done 24 hours after the procedure showed a persistent lung collapse with no interval change. She was initiated on aggressive chest physiotherapy and incentive spirometry to recruit the lung for up to 3 days and continued on antimicrobials despite no sign of obvious infection, with no clinical improvement.
A case conference held with the multi-disciplinary team suggested a second CT scan or a repeat rigid and flexible bronchoscopy to investigate cause of the airway obstruction or endobronchial lesion with a possibility of a thoracotomy and open surgical approach.
Flexible bronchoscopy done on day 8, found an endobronchial lesion completely occluding the left main bronchus slightly below the carina that could not be suctioned. The right bronchial tree was normal. Rigid bronchoscopy was done and we found a tenacious mass, soft to firm in consistency extending to the segmental branches with attendant bronchial wall inflammation throughout. Mucoid discharge was noted from the left basal inferior segment. Multiple segments of thick mucoid/lipoid like material and bronchial casts suggestive of PB were extracted by use of forceps through the rigid bronchoscope and eventual bronchial toilet to conclude the procedure.
Immediate post bronchoscopy period there was minimal oxygen requirements, no respiratory distress, marked improvement in air entry on the left lung zone and we managed to wean off oxygen within 24 hours (Fig. 3).
The team began a regime of combined inhaled corticosteroid with a long-acting beta-agonist (ICS/LABA) and a 3-day course of intravenous methylprednisolone, continuation of chest physiotherapy and incentive spirometry as a deep breathing exercise to improve her lung capacity after lung collapse, antimicrobials and other supportive management. She remained hemodynamically stable with no respiratory distress, vitally stable off oxygen, alert and ambulant. Cardiac sonography was done to also rule out complications from the upper airway obstruction and was normal.
Microscopy showed a suppurative and mixed inflammatory cellular debris with mainly neutrophils and eosinophils. Necrotic debris and flakes of squamous epithelium were also noted. No foreign body material could be discerned (Fig. 4).
Further tests for Immunoglobulin E (IgE) 0.53Ku/l (<90) and Aspergillus Fumigatus IgE were negative.
She was discharged on day 12 on the ICS/LABA and a plan to complete 3 more courses of monthly pulsed methylprednisolone with possibility of adeno-tonsillectomy if upper airway symptoms of obstruction persists. Post discharge she's doing well, no further symptom and normal chest exam and x-ray after the 3rd course of methylprednisolone, her dental carries were filled and no further upper or lower airway symptoms persist. | africa, children, foreign body airway, left lung collapse, plastic bronchitis | CT scan chest before bronchoscopy. (A) Coronal section shows a soft tissue density lesion obstructing the left main bronchus (arrow). |
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PMC8569588_01 | Female | 7 | A 7 year old girl presented with a 2 week history of a persistent dry cough, nasal congestion and mild rhinorrhea that progressed to acute onset left-sided chest pain and difficulty in breathing with a low-grade fever. She had no present or past history of wheeze, no easy fatigability or dyspnea on exertion, no body or feet swelling. No history of close contact with a patient known to have tuberculosis (TB) or severe acute respiratory syndrome coronavirus 2 disease (COVID-19) no loss of weight or poor growth, no loss of appetite nor night sweats reported. There was no known history of chest trauma.
At the onset of her symptoms she was initially managed at home as nasopharyngitis with a cough syrup with no resolution of symptoms. She was reviewed in the outpatient clinic with a diagnosis of pneumonia a few days later and standard antibiotics were prescribed. 3 days later she was reviewed by the paediatrician due to the persistent cough and difficulty in breathing. Inhaled salbutamol and oral montelukast were added as treatment for possible asthma. A further 3 days later she developed chest pain that necessitated an admission.
The birth and developmental history were unremarkable. She had no previous admission but had allergy symptoms since infancy which included eczema, history of skin eruptions with ingestion of animal proteins and allergic rhinitis with upper airway obstruction symptoms.
Her clinical examination on admission; temperature of 37.5 C, blood pressure (BP) 98/53(mean BP 63), heart rate (HR) 105, oxygen saturation (SPO2) 93% on room air and increased respiratory rate of 33 breaths per minute.
The respiratory examination revealed tracheal shift to the left side, dullness on percussion and reduced air entry on the left lung zone all indicating left lung collapse (Fig. 1). Systemic examination was positive for orbital shiners, enlarged inferior turbinates and lingual tonsils hypertrophy, dental carries and lastly mild eczema patches on her trunk.
Initial blood gas analysis done showed compensatory respiratory alkalosis and hypoxia: (pH) 7.426, partial pressure of carbon dioxide (PCO2)25.4 mmHg, partial pressure of oxygen (PO2)55 mmHg, base excess (BE)-8mmol/L, serum bicarbonate (HCO3)16.7mmol/L, total carbon dioxide (TCO2)17 mmHg, oxygen saturation (SPO2)90% and lactate 0.65mmol/L. Normal values for Abbott blood gas analysis machine i-STAT CG8+: pH (7.35-7.45), PaO2 (80-105 mmHg), PaCO2 (35-45 mmHg), BE (-2 to +3 mmol/L), HCO3 (22-26 mmol/L), TCO2 (23-27 mmHg), SPO2 (95-98%), lactate 0.36-1.25mmol/L.
The patient was admitted to the high dependency unit (HDU) due to features of compensated respiratory failure for monitoring, oxygen supplementation, intravenous fluids and intravenous antibiotics.
A working diagnosis of features of lung collapse/consolidation, pneumonia and possible foreign body aspiration.
Initial investigations were as follows: Haemogram and serum biochemistry were normal, the inflammatory/infective markers C-reactive protein (CRP) and Pro-calcitonin (PCT) were low and blood culture was negative. Multiplex respiratory panel polymerase chain reaction test (PCR) was negative for viruses and atypical bacteria tested, tuberculosis microbiology and PCR was also negative. COVID-19 test was also negative. Vitamin D levels were low at 22.9 (30-100) U/L.
Based on her clinical and laboratory findings, an additional diagnosis of; upper airway obstruction, due to adenotonsillar hypertrophy, dental carries, eczema and Vitamin D deficiency was made. She was started on intravenous ceftriaxone and flucloxacillin, skin emollients and Vitamin D supplementation. By the second day she had increased work of breathing and was started on continuous positive airway pressure (CPAP) non-invasive ventilation by mask alternating with a non-rebreather high flow oxygen mask (NRM).
A multidisciplinary consult was sought that included the ear, nose and throat specialist (ENT), pulmonologist and the cardiothoracic surgeon. A plan was made for a computerized tomography (CT) scan of the chest, upper airway endoscopy and bronchoscopy with a possible open surgical approach if needed (Fig. 2).
Rigid bronchoscopy was done on day 3 of admission and removal of a small fat like consistency foreign body from the left main bronchus. It was noted that there was minimal mucus in the trachea and no features of major lower airway inflammation of the visualized segment. Grade 3 fibrotic tonsils and enlarged adenoids were confirmed.
Further history revealed that she had choked on chewing gum 2 months prior to presentation but had not experienced any significant respiratory symptoms warranting a review.
She was maintained on oxygen supplementation by NRM on that day, which was being weaned off gradually as tolerated and remained clinically and vitally stable.
By the second day post-bronchoscopy, we managed to wean off oxygen to 1Litre/min via nasal prongs with no respiratory distress. However, there was still minimal air entry on the left upper and mid lung zones. A repeat CXR done 24 hours after the procedure showed a persistent lung collapse with no interval change. She was initiated on aggressive chest physiotherapy and incentive spirometry to recruit the lung for up to 3 days and continued on antimicrobials despite no sign of obvious infection, with no clinical improvement.
A case conference held with the multi-disciplinary team suggested a second CT scan or a repeat rigid and flexible bronchoscopy to investigate cause of the airway obstruction or endobronchial lesion with a possibility of a thoracotomy and open surgical approach.
Flexible bronchoscopy done on day 8, found an endobronchial lesion completely occluding the left main bronchus slightly below the carina that could not be suctioned. The right bronchial tree was normal. Rigid bronchoscopy was done and we found a tenacious mass, soft to firm in consistency extending to the segmental branches with attendant bronchial wall inflammation throughout. Mucoid discharge was noted from the left basal inferior segment. Multiple segments of thick mucoid/lipoid like material and bronchial casts suggestive of PB were extracted by use of forceps through the rigid bronchoscope and eventual bronchial toilet to conclude the procedure.
Immediate post bronchoscopy period there was minimal oxygen requirements, no respiratory distress, marked improvement in air entry on the left lung zone and we managed to wean off oxygen within 24 hours (Fig. 3).
The team began a regime of combined inhaled corticosteroid with a long-acting beta-agonist (ICS/LABA) and a 3-day course of intravenous methylprednisolone, continuation of chest physiotherapy and incentive spirometry as a deep breathing exercise to improve her lung capacity after lung collapse, antimicrobials and other supportive management. She remained hemodynamically stable with no respiratory distress, vitally stable off oxygen, alert and ambulant. Cardiac sonography was done to also rule out complications from the upper airway obstruction and was normal.
Microscopy showed a suppurative and mixed inflammatory cellular debris with mainly neutrophils and eosinophils. Necrotic debris and flakes of squamous epithelium were also noted. No foreign body material could be discerned (Fig. 4).
Further tests for Immunoglobulin E (IgE) 0.53Ku/l (<90) and Aspergillus Fumigatus IgE were negative.
She was discharged on day 12 on the ICS/LABA and a plan to complete 3 more courses of monthly pulsed methylprednisolone with possibility of adeno-tonsillectomy if upper airway symptoms of obstruction persists. Post discharge she's doing well, no further symptom and normal chest exam and x-ray after the 3rd course of methylprednisolone, her dental carries were filled and no further upper or lower airway symptoms persist. | africa, children, foreign body airway, left lung collapse, plastic bronchitis | CT scan chest before bronchoscopy. (B) Resultant left lung collapse on the axial view (arrow). |
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PMC2713984_01 | Male | 48 | Case 1. A 48-year-old man with liver cirrhosis which led to massive variceal bleeding was referred to us for a transjugular intrahepatic portosystemic shunt (TIPS) procedure. After accessing the portal venous system via the right internal jugular route using a Colapinto transjugular cholangiography/liver biopsy set (Cook, Bloomington, Ind., U.S.A.), we dilated the parenchymal tract between the middle hepatic and left portal vein using a 10 mm-diameter Ultrathin Diamond balloon catheter (Medi-Tech/Boston Scientific, Watertown, Mass., U.S.A.). We tried to place a 10 mm-diameter, 8 cm-long Niti-S stent (Taewoong, Seoul, Korea) in the tract, but during deployment it migrated caudad to the main portal vein (Fig. 4A). A guidewire was inserted into the stent's central lumen, and an Amplatz gooseneck snare, its loop 25 mm in diameter, was introduced over it and positioned around the stent (Fig. 4B). After capturing and pulling the far proximal end of the stent by tightening the loop (Fig. 4C), we were able to relocate the stent to its appropriate position (Figs. 4C, 4D).
Case 3. A 42-year-old man with chronic renal failure underwent internal jugular venous catheterization at the bedside. During the procedure, the tip of the 8-F internal diameter venous introducer sheath fractured and migrated to the right atrium. Because the fragment moved vigorously in accordance with the patient's heartbeat, it was necessary to prevent its migration to the right ventricle or pulmonary circulation. Under fluoroscopic guidance, we inserted a 10-mm gooseneck snare through the right common femoral vein, successfully grasping the fragment and carefully pulling it back into the inferior vena cava (Fig. 5A). Because the fragment was very stiff and its outer diameter was 10-F, it had to be removed without folding. To this end, we used the modified coaxial technique illustrated in the ex-vivo study (Figs. 3B, 3C), inserting another 12-F vascular sheath (13 cm in length). The puncture site was more cranial to the previous one, used for insertion of the loop snare; the central lumen of the fragment was carefully located using an angiographic catheter and guidewire, and the dilator for the vascular sheath was then introduced over the guidewire (Fig. 5B). The entire retrieval system mirrored the one used in the ex-vivo experiment. After the dilator and the end of the sheath fragment were tightly engaged, the whole system was pulled back until the end of the fragment appeared at the femoral access site. It was grasped with forceps and successfully extracted after release of the loop snare and careful compression of the puncture site (Fig. 5C).
Case 6. A 51-year-old man with renal tuberculosis underwent periodic tube change under fluoroscopic guidance. The external part of the nephrostomy catheter was resected close to the point at which it entered the body, and during the procedure, the remaining catheter fragment was inadvertently dislodged, entering the nephrostomy tract. Several attempts to capture it caused its further migration into the pelvocalyceal system. We used a homemade loop snare and Amplatz gooseneck snare, also employing the 'in-situ loop snare' technique, as described by Savader et al., but because the fragment was tightly wedged against the wall, were unable to withdraw any part of it (Fig. 6A). During the various attempts, we managed to pass the guidewire through the central lumen of the catheter fragment, inserting the Amplatz loop snare over the guidewire and easily capturing the proximal tip of the catheter fragment coaxially (Fig. 6B). A dilator was introduced over the guidewire to eliminate the shoulder between it and the cut catheter end and to allow smooth extraction with minimal injury to the access route. The entire system was successfully extracted by simultaneously withdrawing the snare and dilator through the tract (Fig. 6C). The patient was discharged uneventfully after placement of another nephrostomy catheter. | null | Not supported with pagination yet | null |
PMC4760029_01 | Male | 25 | A 25-year-old, 55 kg male presented with severe pain on the right side of the abdomen that radiated to the testicle and the inner side of the thigh, was aggravated on walking and incapacitated him to perform routine work. Other complaints were daytime sedation and loss of job since 5 months. The past history revealed inguinal hernia surgery 6 months back. The patient developed severe pain after 1-month of surgery which progressively increased to hyperalgesia and allodynia. Patient was on regular medical management including per oral diclofenac, paracetamol-tramadol combination, and gabapentin with no relief in pain and had received several interventional pain injections earlier. Systemic and neurological examination was unremarkable. Blood and other investigations were acceptable. After explaining the procedure to the patient, a written informed consent was taken. In the pain management theater, intravenous access was secured, and noninvasive blood pressure, oxygen saturation, and electrocardiograph monitoring were monitored.
Under strict asepsis and a linear high-frequency ultrasound probe (Sonosite, Inc., Bothell, WA 98021 USA) was placed medial and inferior to anterior superior iliac spine. Ilioinguinal-iliohypogastric (II-IH) nerves were identified between the internal oblique and transverses abdominis muscle and a 5 cm, 22 G RF cannula (Cosman Medical Inc., Burlington, MA, USA) was inserted using the in-plane technique. The correct placement of needle tip was verified with sensory stimulation at 50-Hertz frequency and 0.5 volts. Extended duration PRF was applied at 42 C with four cycles of 120 s each (8 min). After negative aspiration for blood, a mixture of 5 ml of 0.2% ropivacaine and 20 mg of triamcinolone was injected. The visual analog scale (VAS) reduced from 100 to 0 in the II-IH territory.
Under strict asepsis, high-frequency ultrasound probe was placed in the right inguinal area. The femoral artery was followed cranially until the spermatic cord was located (above the inguinal ligament) just lateral to the symphysis pubis. On gentle traction of the testis, the spermatic cord was confirmed. The testicular and vas deferens vessels were located with color Doppler. Using an in-plane technique, a 5 cm, 22 G RF cannula was advanced toward the genital branch of the genitofemoral nerve (GGFN) using the in-plane technique. Correct needle positioning was verified with sensory stimulation and motor stimulation. A diagnostic block in GGFN with 5 ml of 0.2% ropivacaine and 20 mg of triamcinolone resulted in preblock VAS of 100 to zero in the right testicular area. However, after 2 weeks, the VAS increased to 50 on movement and after 1-month PRF of GGFN was performed (8 min) using the same methodology described above. The procedure reduced VAS from preblock VAS of 50 on movement to postblock VAS of zero. Thereafter, the patient received Amitriptyline 10 mg once daily at night, Gabapentin 100 mg twice daily and occasional analgesics for 5 months. At present, the patient has resumed his earlier job after a gap of more than 1-year and is now currently not on any analgesics from the past 4 months. The World Health Organization Quality of Life BREF score increased from an initial score of 32 ( first visit in pain management center) to 106 at follow-up of 9 months. | analog pain scale, chronic pain, neuralgia, pulsed radiofrequency | Not supported with pagination yet | null |
PMC6234971_01 | Male | 62 | Mr G, a 62-year-old married man, retired electrician by occupation was brought by his family members with complaints of hearing of voices over the past 10 years. There was no relevant medical history or family history of mental illness. Detailed exploration of history revealed an illness of insidious onset with a continuous and progressive course which was precipitated by interpersonal problems with office colleagues. Following which initially, the patient started to harbour strong fixed false beliefs that his colleagues wanted to defame him with subsequent anger-outbursts, agitation and suspiciousness towards them. Later on, after few months, he even started to hear voices of his office colleagues in clear consciousness discussing him and commenting on his actions using derogatory language. Due to these events, there was significant socio-occupational dysfunction. He was treated with risperidone (2-4 mg/day) with good compliance for a period of 6 months with which there was about 60% improvement but later because of non-compliance and restarting of risperidone he did not show any response. Detailed general physical and systemic examination did not reveal any abnormality and mental status examination was suggestive of auditory hallucinations:third person discussing type, delusions of persecution and reference, low mood and suicidal ideations secondary to psychotic symptoms with absence of insight and intact cognitive functions (Mini mental state examination:28/30). A diagnosis of paranoid schizophrenia as per ICD-10 was considered. After all essential routine haematological (complete blood count) and biochemical investigations (serum electrolytes, liver function tests, lipid profile, renal function tests, serum vitamin B12 and folate), all of which came out to be normal, he was started with Olanzapine 5 mg which was gradually increased to 15 mg over a period of 3 weeks (5 mg increment in dose per week). There was reduction in psychotic symptoms by 40%-50% but on subsequent follow-ups, after 6 weeks of starting Olanzapine, the patient complained of excessive fatigability. On repeat investigations, there was evidence of total leucocyte count of 2600/cumm (baseline:9400/cumm) and total platelet count of 45 000/cumm (baseline:130 000/cumm) without any evidence/history of fever and symptoms suggestive of any local or systemic infection and intake of any other medications. Haematology consultation and detailed autoimmune workup to rule out other possible aetiologies (hepatosplenomegaly, autoimmune antinuclear antibodies and antineutrophil cytoplasmic antibodies) were found to be negative. Following this, a possibility of Olanzapine induced leucopaenia and thrombocytopaenia was considered and the drug was stopped. The patient was admitted for inpatient serial monitoring of haematological parameters and after stopping of Olanzapine, serial monitoring revealed an increase in total leucocyte count (8900/cumm) and total platelet count back to normal range (156 000/cumm) within a week. Later on, he was started on aripiprazole 2.5 mg with a very slow hiking of dosage (2.5 mg/fortnightly) along with monitoring of haematological parameters and psychopathology. At 10 mg of aripiprazole after a period of 30 days, the patient showed significant improvement in mood and psychotic symptoms by around 75% and his haematological parameters continued to remain stable over the next 4-month follow-up period. The prognosis of the patient was good and there was no relapse of any haematological abnormalities. | elderly, hematological adverse effect, olanzapine, schizophrenia, second generation antipsychotics | Not supported with pagination yet | null |
PMC4901172_01 | Male | 57 | The case was a 57-year-old man who presented with abnormal shadows in the left upper lung field on a chest radiograph that was taken during a routine health examination (Fig. 1-A). He had a history of dyslipidemia, which was not treated with medications. Computed tomography (CT) of the chest showed a lung nodule measuring 28 x 20 mm in the left upper lobe. A transbronchial lung biopsy was performed, and the nodule specimen consisted of a granuloma with necrosis. On Ziehl-Neelsen stain, the sputum, bronchial lavage, and nodule specimen were negative. After 6 weeks, the bronchial lavage culture yielded Mycobacterium tuberculosis. Therefore, we made the diagnosis of mycobacterium tuberculoma, and treated the patient with INH (0.3 g/day), rifampicin (RFP) (0.45 g/day), ethambutol (EB) (0.75 g/day), and pyrazinamide (PZA) (1.2 g/day). Three weeks later, he developed fever, headache, and appetite loss. On physical examination, body temperature was 39.1 C, blood pressure was 96/64 mmHg, pulse rate was 112 beats/min, and percutaneous oxygen saturation (SpO2) on room air was 96%. Chest examination was normal, and no lymph nodes were palpable. At this time, a chest radiograph showed diffuse micronodular shadows in both lung fields (Fig. 1-B) and on high-resolution CT (HRCT) of the chest there were diffuse numerous parenchymal micronodules in both lungs such as in hypersensitivity pneumonia (Fig. 2). He was admitted for further evaluation. The white blood cell (WBC) count was elevated to 8700/mul with 67.9% neutrophils, 12.6% lymphocytes, 12.1% monocytes, 6.5% eosinophils, and 0.9% basophils. C-reactive protein and lactate dehydrogenase (LDH) were also elevated to 10.4 mg/dl and 243 IU/l. Other laboratory data including those for liver function, renal function, electrolytes, KL-6 (179 U/ml), and surfactant protein-D (104 ng/ml) were within normal range. Cultures of sputum, urine, and blood showed no growth. We suspected drug-induced pneumonia and stopped the antituberculous drugs, after which his symptoms and diffuse micronodular shadows on chest radiograph and HRCT (Fig. 3, Fig. 4B) rapidly improved without any medication, including corticosteroid. A drug lymphocyte stimulation test (DLST) on a serum sample was performed. As a result, only INH was positive with an increase in the [3H]-thymidine uptake by 219% (normal < 180%), while RFP (112%), EB (90%), and PZA (98%) were negative. Based on this result, we concluded that the pneumonia was induced by INH. Ten days after the cessation of the antituberculous drugs, the patient was discharged. Two weeks after discontinuing the antituberculous drugs, PZA (1.2 g/day) was reintroduced. Although the abnormal shadows and symptoms did not return, liver dysfunction developed, and PZA was discontinued again. Since liver function recovered to normal by only stopping PZA, RFP (0.45 g/day) was reintroduced one week after discontinuing PZA, and EB (0.75 g/day) was reintroduced two weeks after discontinuing PZA. Next, we attempted desensitization to INH over a period of two weeks. The regimen for desensitization was as follows: days 1-3 25 mg/day, days 4-6 50 mg/day, days 7-9 100 mg/day, days 10-12 200 mg/day, and days 13 and 14 300 mg/day. Desensitization to INH was successful, and RFP, EB, and INH were given for 9 months without any adverse events, including recurrence of the abnormal shadows on the chest radiographs and HRCT (Fig. 3, Fig. 4C). | desensitization, drug-induced pneumonia, isoniazid | Not supported with pagination yet | null |
Subsets and Splits