A 79-year-old woman, known case of hypertension, present to the emergency department of our hospital with acute onset of severe posterior neck pain, occipital headache and fever. The patient also had neck stiffness, vertigo, and vomiting. She was admitted to the medical ward and neurological consultation made suspected meningitis. A computed tomography scan of the head was performed, in which serious pathology was excluded. Neurological evaluation was unremarkable, and rheumatologist opinion was sought. The patient admitted long history of neck pain, which was localized, mild, intermittent, and related mainly to activity. However, two weeks before admission, the patient developed severe posterior neck pain which was acute in onset, continuous, radiating into the occipital region, worst at night and associated with vertigo. She experienced gradual worsening of pain and marked restriction of neck motion. The patient reported no weight loss, myalgia, arthralgia, morning stiffness, jaw claudication or visual symptoms. The patient had no prior history of traumatic injury and no apparent history of peripheral joint pain or swelling, apart from mild knee pain with walking and climbing stairs. The patient’s family history was not contributory. Her neck pain improved partially with nonsteroidal anti-inflammatory drug which was used for few days only. On examination the patient was conscious, alert, fully oriented. She looks pale, ill. Vital signs were stable apart from temperature which was 37.8 °C. The superficial lymph nodes were not palpable. Furthermore, edema formation or skin eruption was not noted in her extremities and temporal artery was normal on palpation. Cardiac, respiratory, and abdominal examinations were unremarkable. In terms of neurological evaluation, overall cranial nerve, motor, and sensory nervous systems were intact with no detectable focal neurological deficit and negative Kernig’s sign. On local examination, there was severe cervical rigidity, diffuse tenderness over the spine and paraspinal muscles, most marked in the nape of the neck with severe muscle spasm. Passive cervical spine movements were significantly reduced. Range of neck motion was limited to 10 degrees on rotation and lateral flexion whereas extension and flexion were 20 degrees each. At the end of the range of neck motion, pain was markedly provoked. The peripheral joints were not tender or deformed, apart from knees which showed medial joint line tenderness, crepitus, and mild painful limitation of the range of motion. Regarding the laboratory data, the value of the C-responsive protein was 5.28 mg/dL (normal range, 0.0–0.5 mg/dL); leukocyte was 13600/mm3, 86% neutrophils, erythrocyte sedimentation rate was 21 mm/hour, all of the other findings including liver, kidney, and thyroid function test, serum electrolyte, blood sugar, uric acid and urinalysis were unremarkable. Blood cultures were negative. Cervical spine radiography obtained 2 weeks prior to the admission showed only cervical spondylosis with loss of cervical lordosis (
). Recent radiograph of the knees revealed advance osteoarthritis, with no evidence of chondrocalcinosis. Based on the clinical features, pyogenic spondylodiscitis was highly suspected and cervical magnetic resonance imaging was ordered which revealed soft tissue thickening posterior to the dens, with low-intermediate signal intensity on T1 and low signal intensity onT2-weighted, with advance multilevel degenerative changes and spinal cord compression (
). A plain computed tomography (CT) scan and three-dimensional (3D)-reconstruction imaging of the cervical spine detected calcification in the soft tissue surrounding the dens and on its top on coronal reconstruction (
), linear calcification posterior to the dense of axis on sagittal reconstruction (
) and faint dotted calcifications of the trans-verse ligament of the atlas on axial imaging (
). CT imaging also revealed narrowing of the atlantoaxial joint with osteophytosis. There was no evidence of osseous destruction, lytic lesions, or fractures. A diagnosis of crown dens syndrome was made. Initially, the patient was treated symptomatically with analgesic drugs and intravenous fluids. The patient was started on colchicin 0.5 mg and prednisolone 15 mg daily, in addition to omeprazole and cinnarizine. The patient was discharged from the hospital on the next day, and her symptoms drastically improved within 7 days after initiating treatment. Three weeks later, the patient was nearly asymptomatic with marked improvement in cervical range of motion and normalization of the inflammatory markers.


A 58-year-old woman of Polish origin with rheumatoid arthritis presented with fever (temperatures to 38.5°C measured at home) and ulcers on the dorsum of the left foot and in the intergluteal cleft. She had seropositive rheumatoid arthritis for 15 years, which had been difficult to treat and for which she had received treatment with various biological agents: adalimumab, certolizumab pegol and tocilizumab. At the time of presentation, the RA treatment was methylprednisolone 2mg/day, methotrexate 15mg/week and rituximab 2g/6 months. She also had a past medical history of deep venous thrombosis in both legs, hypothyroidism and osteoporosis. Clinical examination on presentation was unremarkable with the exception of the infected ulcers on the dorsum of the left foot and in the intergluteal cleft. Laboratory investigations were remarkable for elevated erythrocyte sedimentation rate (ESR: 34mm) and C-reactive protein (CRP: 83mg/l), while blood cultures were negative. For the treatment of the infected ulcers, ciprofloxacin and clindamycin were administered intravenously (iv) for 10 days and surgical debridement was performed frequently. Eleven days after admission, the patient was discharged on ciprofloxacin and clindamycin per os and hyperbaric oxygen therapy was scheduled in order to facilitate healing of the ulcers.
However, 24 days after discharge the fever relapsed while the ulcers were not improving (), so the patient was admitted again. Apart from fever up to 38.3°C, clinical examination this time revealed subcutaneous nodules on both forearms, while inflammation markers had increased (ESR: 44mm, CRP: 113mg/l). Tissue from the ulcer of the foot was received for culture, which was positive for E. coli. Blood cultures were once again negative. Magnetic resonance imaging (MRI) of left foot was performed in order to exclude the possibility of osteomyelitis and revealed inflammation of soft tissues. Concerning the etiology of ulcers, vasculitis was considered the most likely diagnosis. To delineate the underlying vascular pathology intra-arterial digital subtraction angiography (i.a. DSA) of the lower limbs was performed. DSA demonstrated luminal narrowing of peroneal (fibular) arteries bilaterally, which was significant in left peroneal artery (). These findings supported the diagnosis of vasculitis. Additional immunological workup demonstrated positive rheumatoid factor (RF) and antinuclear antibodies (ANA) and negative anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies, antibodies to extractable nuclear antigens (anti-ENA), perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibodies (p-ANCA, c-ANCA) and cryoglobulins. Therefore, low-dose cyclophosphamide was administered iv (125mg and 250mg, a week apart), resulting in recession of fever and nodules and a decrease of ESR and CRP. In addition, meropenem and clindamycin were administered iv, following the antibiogram of soft tissue culture from the ulcer, and frequent surgical debridement was performed. Furthermore, the patient underwent hyperbaric oxygen therapy daily. Treatment resulted in improvement of the ulcers, thus the patient was discharged 28 days after second admission and a re-evaluation visit was scheduled.
Seven days after second discharge the patient was readmitted, because of fever relapse, agranulocytosis (absolute neutrophil count: 60 cells per microlitre) and oral candidiasis. Inflammation markers had increased even more (ESR: 117mm/h, CRP: 418mg/l), while blood cultures were once again negative. Chest and abdominal CT scan was performed for the exclusion of malignancy and lymphoproliferative disorders and demonstrated only mild hepatomegaly. Hemoglobin and platelet count gradually decreased () and the patient developed pancytopenia on the 4th day of admission. Additional laboratory data showed hyperferritinemia (>1000 mg/dL), hypofibrinogenemia and hypertriglyceridemia. Bone marrow aspiration was performed and demonstrated hemophagocytosis, agranulocytosis and megakaryocytic hypoplasia (). Repeated blood cultures and an extensive workout for infection including serology for Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), toxoplasma and brucella were negative.
The presentation of fever, pancytopenia and hemophagocytosis in bone marrow, following a disease flare in the form of vasculitis, in combination with hepatomegaly, hyperferritinemia, hypofibrinogenemia and hypertriglyceridemia, in the setting of a negative infectious and malignant disease workup, was compatible with the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH). Indeed, the patient fulfilled multiple Histiocyte Society HLH-2004 diagnostic criteria (), including fever, cytopenias affecting all 3 lineages, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis in bone marrow and hyperferritinemia.
For the treatment of secondary HLH, corticosteroids and intravenous immunoglobulin (IVIG) were initiated. Methylprednisolone was administered at 125mg/day intravenously for 3 days, followed by 40mg/day orally. IVIG was administered at 500mg/kg daily for 10 days. The patient was also started on filgrastim subcutaneously, a granulocyte colony-stimulating factor (G-CSF) analog. In addition, empiric broad-spectrum antibiotic therapy for neutropenic fever was initiated, including ceftazidime, clindamycin, vancomycin and caspofungin. Trimethoprim/sulfamethoxazole was also administered for pneumocystis prophylaxis, as well as acyclovir for prevention of reactivation of herpes viruses. Supportive treatment included red blood cell and platelet transfusions and parenteral nutrition.
The treatment led to fever resolution and gradual improvement of anemia, neutropenia, thrombocytopenia and rest laboratory data (). One month after third discharge, the ulcers on the dorsum of left foot and in the intergluteal cleft had healed completely () and complete blood count had returned to normal. The patient is currently on treatment with rituximab 2g/6 months for RA.


A 55-year-old female with no medical history presented with a dry cough for one month associated with decreased exercise tolerance and dyspnea on exertion in addition to bilateral pleuritic chest pain. At baseline, she had no difficulty walking long distances and was able to carry out activities of daily living with no difficulty. However, within the past month, she was only able to walk half a block before becoming short of breath. She denied any recent respiratory illnesses, joint swelling, or muscle weakness. Initial vital signs were temperature of 98°F, blood pressure of 116/76 mmHg, respiratory rate of 18 breaths per minute, and oxygen saturation of 95% on room air. Pulmonary examination revealed bibasilar “Velcro-like” dry inspiratory crackles. Cardiovascular, abdominal, and neurological examinations were unremarkable. Laboratory tests revealed microcytic anemia and no leukocytosis. Routine biochemistry and liver function tests were normal. Her erythrocyte sedimentation rate was 26 (0–15 mm/hr), C-reactive protein 35.9 (0–3 mg/dL), and creatine kinase level were elevated at 464 (21–215 units/L). Urinalysis and hepatitis serology were normal. Chest radiograph showed bibasilar airspace infiltrates more pronounced on the left (). Legionella antigen, Mycoplasma antigen, blood culture, and QuantiFERON Gold were all negative. She was treated for community acquired pneumonia with ceftriaxone and azithromycin but during her hospital course, she continued to desaturate to 80% upon exertion. Computed tomography of the chest showed extensive bilateral lower lobe opacities along with scattered ground glass opacities and peri-bronchial consolidations (). Her gender, age, and radiological findings suspicious for ILD prompted a rheumatology workup, which was positive for rheumatoid factor, antinuclear antibody, cyclic citrullinated peptide, and anti-Jo-1 antibody. A subsequent right quadriceps muscle biopsy revealed active, mild myopathy with focal subtle endomysial fibrosis suggestive of immune-mediated etiology.
She was diagnosed with antisynthetase syndrome presenting primarily with ILD. The patient was started on intravenous pulse dose steroids (1gm methylpredniso-lone) along with mycophenolate mofetil (MMF) resulting in significant improvement in her clinical symptoms. She was discharged home on tapering steroids, MMF, and oxygen supplementation with close follow up. Outpatient treatment with rituximab allowed her to be weaned off oxygen supplementation and eventually regain her baseline level of activity. A follow up computed tomography of the chest showed interval decrease in her bibasilar infiltrates (). Her initial and 5-month post-treatment pulmonary function tests showed an improvement in DLCO and FVC ().
The initial and post-rituximab pulmonary function tests showing marked improvement in patient’s diffusing capacity of the lung for carbon monoxide and forced vital capacity


A 64-year-old female presented to the hospital with the chief complaint of right upper quadrant pain, multiple episodes of non-bilious emesis, and anorexia since undergoing a computer tomography (CT)-guided microwave ablation of an HCC tumor in liver segment IV the day before. The patient’s past medical history was significant for untreated hepatitis C, compensated liver cirrhosis, and HCC stage IA diagnosed in 2017 with a single lesion measuring 1.5 x 2.0 cm in diameter. At the time of presentation, the patient was hypotensive to 81/52 mmHg and tachycardia to 118 beats per minute. Physical examination was significant for scleral icterus, abdominal distension, right upper quadrant tenderness and hypoactive bowel sounds. Laboratory studies demonstrated an aspartate aminotransferase of 2,467 U/L, an alanine aminotransferase of 688 U/L, an alkaline phosphatase of 355 U/L, a total bilirubin of 4.5 mg/dL, and an international normalized ratio of 1.1. CT angiogram of the abdomen revealed thrombosis of left branch of the hepatic artery with hepatic infarct (Figure ). Upon hospitalization, the patient experienced hypoxic respiratory failure, hepatic encephalopathy, transfusion dependent anemia, and hepatorenal syndrome. Her Model for End-Stage Liver Disease-Na scores during admission escalated from 11 to 49 precluding emergent liver transplant and regrettably, the patient expired from multi-organ failure.


We report the case of a 22-year-old pregnant women, G2P1, diagnosed with placenta accreta spectrum (PAS) and referred to our institution at 31 weeks of gestation for further care and management. Earlier, at 25 weeks of gestation, the patient reported vaginal spotting. An ultrasound performed by her primary obstetrician was suggestive of a placenta percreta. At 30 weeks, she experienced a preterm premature rupture of membranes and moderate vaginal bleeding requiring her admission in a primary care hospital. During her stay, she received tocolytics, antibiotics and steroids. Strict bed rest was prescribed but no thrombosis prophylaxis was administered given her history of vaginal bleeding that lasted one week. Upon confirming the diagnosis of placenta previa with accreta spectrum on a pelvic MRI, the patient was referred to our tertiary care center to schedule her delivery.
Eight months earlier, she underwent a cesarean section due to a protracted labor. Postoperatively, she received no prophylactic anticoagulation. Besides, she was taking oral contraceptives for three months because of a persistent vaginal bleeding; she stopped them three months before pregnancy. The patient reported no relevant past medical or surgical events. Her father died at the age of 42 of an ischemic stroke and two uncles had histories of non-specific thromboembolic events.
On admission, the patient was afebrile, hemodynamically stable and did not complain of pelvic pain. She noted only light to moderate persistent vaginal bleeding. Urgent ultrasound showed a viable fetus with appropriate biometrical parameters and no amniotic fluid. Fetal cardiotocography revealed regular uterine contractions. She underwent urgent delivery by cesarean section and hysterectomy under general anesthesia according to our specially developed technique [, ]. The placenta was previa, anteriorly located and slightly lateralized to the left and reached the uterine serosa without perforating it. The placenta was bulging under a thin uterine serosa with a lot of neo-vascularization at this level.
The total estimated blood loss during surgery was 1800 ml. This large amount of intraoperative bleeding was essentially from the vagina, which was unfortunately uncontrollable before removing the uterus completely. The anesthesiologist in charge had to transfuse the patient with allogenic red blood cells (RBC; 7 units), fresh-frozen plasma (FFP; 6 units) and platelets (1 unit) to maintain her hemodynamic stability. Since more than four RBC units were transfused in less than one hour, the transfusion was considered massive and 1:1 ratio of FFP to RBC scheme was used. At the end of surgery and transfusion, an evaluation of complete blood count (CBC) revealed a hematocrit level of 32% and hemoglobin level of 10.8 g/dl. The patient was also normothermic and hemodynamically stable. She was waked up from anesthesia and was transferred to ICU for postoperative surveillance. At ICU admission, she was hemodynamically stable with normal neurologic examination.
Two hours later, the patient became cyanotic and went into cardio pulmonary arrest. Cardiac monitoring showed pulseless ventricular tachycardia. Arterial blood gases showed hypocapnia (PaCO2 of 30 mmHg) and hypoxia (PaO2 of 61 mmHg). Characteristic S1Q3 wave detected on electrocardiography was associated with hypoxia and hypocania, which were highly suggestive of pulmonary embolism (PE). She was intubated and received 40 min of cardiopulmonary resuscitation. A transthoracic echocardiogram done in ICU showed a thrombus in the right ventricle. Urgent pulmonary angiogram after hemodynamic stabilization confirmed the diagnosis of bilateral massive PE (Fig. ).
So the patient underwent an urgent thoracotomy and an extracorporeal circulation was used. During surgery, a simultaneous transesophageal cardiac ultrasound was done showing a dilated right ventricle containing clots. A pulmonary artery thrombectomy was performed and multiple clots were retrieved from the pulmonary artery (Fig. ).
Once the situation was stabilized, an inferior vena cava filter was placed via an abdominal incision and external iliac vein catheterization. After weaning from extracorporeal circulation, an intraoperative transesophageal cardiac ultrasound revealed the presence of a new free-floating thrombus in the right atrium and right ventricle (). A second extracorporeal circulation using new cannulation of the large vessels was initiated and a second embolectomy was performed. The patient was transferred to the cardiac surgery care unit (CSU) for surveillance. While at CSU, she was placed on therapeutic intravenous heparin for anticoagulation and had compressive pneumatic stockings in place at all times.
Two days later, the patient experienced a major hemoperitoneum with distended abdomen and tachycardia due to massive anticoagulation that necessitated a second laparotomy to achieve hemostasis. Only blood clots were found in the peritoneal cavity without active source of bleeding. All vascular pedicles were controlled and the vaginal cuff was re-sutured. Intraoperative evaluation of CBC revealed a hematocrit level of 26% and hemoglobin level of 8.7 g/dl. Intraoperative allogeneic RBC (4 units) and FFP (5 units) were transfused. The rest of her post-operative course was uneventful.
The patient was discharged on postoperative day 13. She received acenocoumarol per os for a lifetime anticoagulation. A follow-up was organized with a hematologist to perform a full thromboembolic disease work-up. A panel of tests for hypercoagulability was performed and showed: protein S deficiency, presence of circulating lupus anticoagulant, heterozygous methylenetetrahydrofolate reductase (MTHFR) mutation and genotypes of plasminogen activator inhibitor (PAI), human platelet antigen (HPA), angiotensin converting enzyme (ACE), and apolipiprotein E (Apo E) with a moderate risk for thrombosis.
The pathologic report confirmed the diagnosis of abnormally invasive placenta type percreta (grade 3a, according to FIGO classification): hysterectomy specimen showing villous tissue reaching the uterine serosa and in multiple places breaching the serosa and invading the extrauterine adipose tissue with a fibrous reaction at this level.


A 79-year-old man was admitted to our operative unit for treatment of primary lung cancer located in the right lower lobe. He was classified as stage IIA, according to the eighth edition of the TNM staging system for lung cancer, and scheduled for video-assisted thoracoscopic right lower lobectomy. Preoperative enhanced chest computed tomography (CT) scans showed a mass in the lower lobe of the right lung, measuring 48 × 32 mm and anatomical variations of pulmonary venous drainage including separate drainage of the superior segment right lower lobe vein (V6) from the basilar segments right lower lobe vein into the left atrium; middle lobe veins (V4 and V5) were found to empty into the V6 and accessory V6 passing behind the right lower lobe bronchus (Fig and ). During video-assisted thoracoscopic surgery (VATS) lobectomy, after a careful hilar dissection and division of the anterior part of the major fissure, the inferior pulmonary vein was divided with a vascular stapler ensuring preservation of middle lobe venous drainage (Fig ). Moreover, the correct identification of an accessory V6 during the posterior mediastinal lymph node dissection, allowed intraoperative bleeding to be avoided (Fig ). The patient had an uneventful postoperative course and the pathological examination of the resected specimen resulted in a diagnosis of T2bN0M0 adenocarcinoma.


We report a 40-year-old male admitted with episodic high-grade intermittent fever, nonproductive cough, and shortness of breath for a duration of three days. Two years ago, he got admitted to hospital with a similar febrile respiratory illness which was managed as severe pneumonia with a poor response to antibiotics. On examination, the patient was ill-looking, febrile, and dyspneic with a respiratory rate of 28 cycles per minute with bilateral lower zone crepitations in the lungs. He had tachycardia (110 beats per minute) with normal blood pressure. Neurological and abdominal examinations were unremarkable. His oxygen saturation was 90% on air, and arterial blood gas showed a type 1 respiratory failure.
Initial investigations revealed a white blood cell count of 18,100 per microliter with 90% neutrophils. The platelet count was 22,4000 per microliter. C-reactive protein was 145 milligrams per liter. Chest radiograph revealed bilateral, diffused, middle, and lower zone alveolar shadows (). Blood culture and sputum culture for bacteria were negative on 3 repeated occasions. Throat swabs for influenza antigen, myocoplasma serology, and legionella urinary antigen were negative. The patient was initiated on intravenous amoxicillin and clavulanic acid with oral clarithromycin. He did not show a favorable clinical response to treatment, and his clinical symptoms and blood investigations continued to deteriorate despite treatment. On day 5 of admission, he was transferred to an intensive care unit and started on noninvasive ventilation to maintain oxygenation. His antibiotics were changed to intravenous meropenam and vancomycin. Repeated complete blood count had revealed a white blood cell count of 34,400 per microliter; 94% of them were neutrophils, 2% were lymphocytes, and the platelet count was 462,000 per microliter. Other tests showed a C-reactive protein of 433 (<6.0) mg/L, serum total bilirubin of 17 (1.71–20.5) micromoles per liter, serum creatinine was 74 (60–110) micromoles per liter, and blood urea was 19 (7–20) milligrams per deciliter. Serum alanine transaminase of 85 (7–40) u/L, serum aspartate transaminase of 74 (7–40) u/L, and prothrombin time of 14 seconds with an international normalization ratio of 1.3 were shown. Urine analysis was normal.
Serum ferritin was 17,400 (<300) ng/ml. Blood film has shown severe neutrophil leukocytosis with left shift and toxic granules. Ultrasound scan of the chest has revealed consolidations in both middle and lower lobes of the lungs, and there were small bilateral pleural effusions (). Ultrasound-guided aspiration of right-side pleural collection revealed 1600 polymorphs per microliter, 50 lymphocytes per microliter, and 250 red cells per microliter. The pleural fluid protein concentration was 31 grams per deciliter, and pleural fluid sugar was 80 (<81) milligrams per deciliter. The pleural fluid lactate dehydrogenase level was 486 (0–248) iu/L, and pH was 7.3. It was an exudate according to light criteria. Pleural fluid bacterial, mycobacterial, and fungal cultures were negative. Repeated blood and sputum cultures were negative. At the same time, he developed continuous central chest pain on day 6 of illness. ECGs revealed dynamic ST segment elevations in leads V2 to V6 and P wave inversion in leads V3 and V4. Cardiac Troponin I titer was 0.58 (0.00–0.40) nanograms per milliliter after 6 hours since the onset of chest pain and 2D echocardiogram was normal. He was managed as a probable myocarditis complicating severe pneumonia.
Over the course of next three weeks, he was given intravenous broad-spectrum antibiotics for 7 days. Due to poor response, antibiotic regimen was changed to intravenous Piperacillin-Tazobactam on the 15th day of illness. It was continued for five more days without much success. The repeat ferritin concentration was found to be > 100,000 ng/ml, which was above the laboratory detection level. To look for non-infective pathology, a comprehensive panel of autoimmune markers was carried out. Serum level of ANA, cANCA, and pANCA, rheumatoid factor, and anti-DsDNA remained normal. Serological tests for HIV and syphilis (VDRL and TPHA) were also negative.
He was started on indomethacin 50 mg three times a day assuming the possibility of Still's disease on the 20th day of illness. Although steroids are the preferred choice in AOSD, possibility of severe pneumonia was not completely ruled out at that time, and starting of steroids was considered dangerous. The patient had a rapid response to initiation of indomethacin and became afebrile within next 24 hours and had significantly improved vital parameters. After 48 hours, the patient was taken off from BiPAP ventilation. He was transferred out of ICU, and he could breathe on normal air on the 23rd day of illness. Piperacillin-tazobactam was continued along with indomethacin for further 12 days. The patient remained afebrile and clinically improved and regained appetite and weight. The white blood cell count came down to 12,100 cells per microliter. C-reactive protein came down to 65 iu/L. Chest radiographs () revealed few bilateral radio-opaque areas in both lower zones of lung fields, indicating resolving pneumonia. He could move and attend his day-to-day routine activities. A complete diagnosis of pulmonary onset AOSD was made, and treatment was continued. Steroids were not considered, as the patient has already responded well.
On the 35th day of illness, the patient developed re-emergence of moderate-grade intermittent fever while on indomethacin. Hospital-acquired infections were excluded by repeating cultures and serological studies. Fever appeared 2 to 3 times each day. He continued to have a good appetite. But, he developed joint pains on both knees and ankles, and he developed a pink-colored maculopapular rash on both upper and lower limbs which lasted for 2 days. He also had generalized lymphadenopathy for the first time during the hospital stay. He also had generalized lymphadenopathy for the first time during the hospital stay which were multiple, firm, mobile, and nontender in bilateral cervical, axillary, and inguinal lymph node groups. His respiratory examination and other system examinations were unremarkable. Left cervical lymph node biopsy was histologically compatible with Kikuchi lymphadenitis that has demonstrated abundant karyorrhectic debris and a proliferation of histiocytes and plasmacytoid cells ().
He was given intravenous methyl prednisolone 1 g/daily for three days and later converted to oral prednisolone. All antibiotics were discontinued. Soon after starting steroid treatment, the patient demonstrated signs of complete improvement. He was afebrile, and his joint pains disappeared. Lymph nodes were impalpable after 10 days since the initiation of steroids. The patient was discharged on the 42nd day of illness. On follow-up after first and six months, he continued to have a good health. Oral prednisolone was continued and gradually tailed off over the next 6 months.


A 10-year-old male was found in an unconscious state after being knocked down by a car while crossing the road. He had regained full consciousness by the time he was brought to the hospital. He complained of pain over his head and neck, and a paediatric cervical hard collar was applied. Primary and secondary surveys were done; a scalp laceration over the right parietal area was duly sutured. No other injuries were noted.
The CT brain was normal. However, his cervical CT showed discontinuity of anterior arch of atlas (Figure ).
The initial impression was a rare sub type of Jefferson Type 1 fracture, whereby only the anterior arch of atlas is fractured []. However, upon reviewing the CT scan findings, the fracture line was noted to be smooth with presence of sclerosis, as opposed to a fracture line which would be slightly jagged with sclerosis, only a late feature which is associated with the healing process. Furthermore, the patient subsequently was pain free and had full range of motion of his neck without any pain or neurological symptoms. The patient’s diagnosis was then revised as non-fusion of anterior arch of atlas with failure of anterior midline synchondrosis formation. Following clinical confirmation of spinal stability, the cervical collar was removed and the patient was discharged home well after being observed for possible signs and symptoms of neurological deterioration.


A 60-year-old Asian female presented to our emergency department with malaise and nausea. Her medical history was significant for polymyositis and type 2 diabetes from long-term steroid use, maintained on metformin. She did not have any family history of diabetes. Her symptoms included decreased appetite, generalized fatigue and nausea for a week that got worse over the last 2 days. The patient was on tacrolimus 6 mg BID, azathioprine 200 mg daily, and low dose prednisone 7.5mg, which was tapered down from 20mg daily as her muscle enzymes normalized on her last clinic follow up. Recently, she was started on fluconazole 200mg daily for 14 days for oral and vulvovaginal candidiasis from long-term steroid use. Occasional blood glucose levels, done earlier during follow-up clinic visits, were below 150. Physical exam was remarkable for oral thrush.
Her initial fingerstick was greater than 600. On lab investigations, she was found to have an anion-gap metabolic acidosis attributed to ketoacidosis with bicarbonate levels of 15, gap of 29, potassium 3.9 and glucose 837. Serum beta hydroxybutyrate was elevated. Arterial blood gas showed a pH of 7.29 and PCO2 20. Urinalysis showed ketonuria and glucosuria. Glycated hemoglobin was 7.2%. Tacrolimus trough level was 25. Infectious etiology for hyperglycemia was ruled out.
The patient was started on insulin drip and intravenous fluids, and her electrolytes were corrected. Her acid-base status improved within the next 48 hours. She was switched to subcutaneous insulin and a regular diet on the floor. Considering the diabetogenic potential of TAC, it was decreased to 2mg BID while continuing fluconazole; background prednisone therapy was discontinued and azathioprine was continued at the same dose. Daily insulin requirements in the hospital were 20 units of long-acting and 3 units of short-acting. The patient was given education about injecting insulin at home and discharged on a diabetic diet and subcutaneous insulin. She was closely followed up upon discharge for monitoring blood glucose levels (). As the patient completed her fluconazole therapy, her insulin requirements began to decrease drastically.


A 62-year-old female presented with two-year exertional dyspnea. Her dyspnea progressively worsened and severe pitting edema of the lower extremities appeared, so she visited her previous doctor and took an electrocardiography which revealed right heart overload. Blood examination showed that the value of brain natriuretic peptide (BNP) was 537 pg/ml. Echocardiography revealed that the ejection fraction was 78.7%. Tricuspid regurgitation pressure gradient (TRPG) was elevated to 92 mmHg, and the right atrium, right ventricle, and inferior vena cava were enlarged. The cardiac catheter test revealed that the mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure, and pulmonary vascular resistance (PVR) levels were 54 mmHg, 8 mmHg, and 13.7 Wood, respectively. The pulmonary function test revealed the percent vital capacity (%VC), FEV1.0%, and percent diffusing capacity of the lung for carbon monoxide (%DLCO) to be 117%, 82%, and 55%, respectively, thus suggesting the involvement of the lungs with impaired diffusion but not with restrictive and obstructive pulmonary disorder. Her chest X-ray and computer tomography did not reveal any pulmonary complications (). She was diagnosed with group I PAH according to the Nice classification of PH. Serological analysis revealed antinuclear antibody (ANA) to be negative; however, the centriole pattern of staining was observed with high titers (1 : 640) using indirect immunofluorescence (). Then, she was introduced to our hospital. The patient also manifested DUs, nailfold bleeding, telangiectasia (), and Raynaud's phenomenon but no skin sclerosis when she visited us. She has never noticed her digital sclerosis. Based on the 2013 classification criteria for SSc by the American College of Rheumatology/European League against Rheumatism, the patient was subsequently diagnosed with SSc [] (). She was initially treated with oral vasodilators and diuretics. Beraprost (120 μg/day) and riociguat (1.5 mg/day) as vasodilators were prescribed and azosemide (60 mg/day), spironolactone (25 mg/day), and tolvaptan (3.75 mg/day) as diuretics were also prescribed in order. As edema of the lower limbs worsened immediately after macitentan was started, its use was discontinued. Dyspnea was not completely improved with beraprost and riociguat. Although we considered continuous intravenous infusion of epoprostenol as an additional therapy, the patient refused because of issues concerning aesthetics and quality of life. Therefore, we discussed with cardiologists and suggested the use of immunosuppressive therapy, which might be effective owing to the positivity of the anticentriole antibody, a unique immunological abnormality strongly associated with SSc-PAH. Moderate doses of prednisolone (PSL; 30 mg/day) and intravenous cyclophosphamide (IVCY; 500 mg every four weeks) were initiated. After two months, these immunosuppressive therapies and vasodilators improved mPAP from 47 to 33 mmHg, 6-minute walk distance (6MWD) from 418 to 480 m, and PVR from 8.7 to 6.0 Wood. Interestingly, the anticentriole antibody also disappeared and was not detected 16 months with a slight decrease of immunoglobulin G (IgG) after the treatment. After 10 times IVCY, azathioprine (50 mg/day) was started, and PSL was gradually decreased and maintained at 5 mg/day. To achieve further improvement, a new vasodilator selexipag was added and increased up to 2 mg/day in addition to riociguat (7.5 mg/day) and beraprost (360 mg/day). PAH has been well controlled using these treatments ().


A 44-year-old gentleman was referred to the vascular surgery team by his GP with a several month history of a lump on the volar aspect of his right hand. He did not recall any significant or repetitive trauma. His past medical history includes only well-controlled asthma and primary Raynaud Syndrome. Of note, he is a musician and has played multiple instruments, including saxophone, clarinet, piano and guitar, for most of his life. He is also a regular golfer. He has no family history of aneurysms and is a lifelong non-smoker.
An initial ultrasound scan showed a pulsatile, anechoic sac measuring 18.9 × 9.3 mm in size, consistent with an aneurysm. A subsequent magnetic resonance angiogram (MRA) confirmed a 16 × 7 mm saccular aneurysm of the common digital artery between the middle and ring fingers (). The dynamic contrast study showed good collateral supply to the right middle and ring fingers. The patient was referred to the plastic surgery hand team due to concerns with the potential complexity of surgical management.
After discussion with the team, the patient opted to proceed with surgical excision and understood that a vein graft may be required if blood supply to the fingers was affected by removal of the aneurysm.
Preoperative modified Allen test was normal and the patient underwent excision of the lesion as a day case procedure under a general anaesthetic with brachial plexus block supplementation and arm tourniquet. The lesion was confirmed intraoperatively as a true aneurysm of the common digital artery supplying the radial side of the right ring finger and ulnar side of the right middle finger (). The aneurysm was clamped both proximally and distally and good distal perfusion was confirmed (). The aneurysm was excised and sent for histology, both ends were tied off and the skin closed. Perfusion of the fingers was confirmed after application of dressings. Histology confirmed the diagnosis of true aneurysm. At one-month follow-up the patient had no ongoing sequelae.


A 47 year-old Black female with a past medical history of congestive heart failure (ejection fraction (EF) which improved from 30% to 55%), known coronary artery disease with ST elevation myocardial infarction status post percutaneous coronary intervention to the mid left anterior descending artery a year prior to presentation, as well as hypertension, hyperlipidemia, diabetes mellitus type 2, came with chest pain at rest. EKG revealed normal sinus rhythm, old anteroseptal infarct, left atrial enlargement and was unchanged from prior EKGs. Two sets of troponins were negative. Echocardiogram showed EF of 60%, grade 1 diastolic dysfunction and mild hypokinesis of the anteroseptal wall. Patient was referred for coronary catheterization due to unstable angina. At the start of the procedure, the patient was hemodynamically stable and received local lidocaine injection to the right radial area, as well as a radial cocktail consisting of 3000 units of heparin, 2.5mg of verapamil, 100 mcg of nitroglycerin. She also received 1 mg of IV midazolam and 25 mcg of IV fentanyl for sedation. At that time the patient’s vital signs were recorded as blood pressure of 151/104 mm Hg and heart rate of 120 BMP. 35 minutes into the case, after completion of the diagnostic part of the left heart catheterization, she complained of need to urinate but being unable to do so. Shortly after, she began to experience palpitations, diaphoresis and shortness of breath, as well as nausea, pelvic and lower back pain. Her blood pressure dropped to 103/74 mm Hg and heart rate decreased to 73 BPM. Hemodynamic monitor revealed variable PR prolongation followed by an episode of complete heart block lasting 28 seconds. The heart block reverted spontaneously to normal sinus rhythm and the patient did not experience syncope. The procedure was halted; patient was sat up and given an IV normal saline bolus. A foley catheter was inserted, which immediately drained 600 cc on clear yellow urine and was clamped to avoid further hypotension and hematuria. It eventually drained 1L urine total. As soon as the Foley catheter was inserted, patient reported resolution of symptoms, with blood pressure recovering to 146/103 mm Hg, heart rate 122 BPM. The rest of the diagnostic case, including right heart catheterization and left ventriculogram, was completed uneventfully. Patient was not found to have any new obstructive coronary disease and evaluation of the left ventricle ejection fraction was compatible to the echocardiogram results.


Patient 1 with anti-AMPAR encephalitis: This was a 66-year-old woman with type 2 diabetes mellitus. She was diagnosed as having left breast invasive ductal carcinoma and was scheduled to have mastectomy surgery. The surgery was successful; pathologist reported the cancer as invasive ductal carcinoma, grade 1, pT2, ER (+), PR(+), Her2(−). However, ataxic gait and acute psychosis with auditory hallucination, agitation, uncontrolled rage, progressive aphasia, anterograde amnesia, confusion, and disorientation developed 3 days after cancer surgery. Infectious and metabolic etiologies were excluded from complete surveillances. MRI of the brain revealed only few spots of white matter hyperintensities. EEG did not find epileptiform discharge. The cell-based assay found anti-AMPAR antibodies in her CSF and serum. She was diagnosed as having anti-AMPAR encephalitis and started immunotherapy at the 8th week after the symptom onset. FDG-PET/CT at the 9th week indicated extensive hypometabolic areas including the prefrontal, orbitofrontal, temporal parahippocampal, and posterior parietal areas (Figure , scan 1). The patient received methylprednisolone pulse therapy by 1 mg/day, followed by oral prednisolone 0.5–1 mg/kg. She also completed 12 sessions of plasmapheresis. Amantadine 200 mg/day as a NMDAR antagonist was used to control limb unsteadiness. Quetiapine 75 mg/day controlled her psychosis. Her consciousness and ataxia gradually improved. Six months later, the patient was independent (mRS score 1) with only mild ataxic gait and mild difficulties in the comprehension of complex sentences remained. The follow-up FDG-PET demonstrated that the hypometabolism was resolved (Figure , scan 2). Compared with the cognitive performance at the time of the first PET scan, the scores in the second PET scan were significantly improved; MMSE improved from 12 to 24 points and MoCA from 4 to 18 points. The years of school education of this patient was 3 years.


Patient 2 with anti-NMDAR encephalitis: This was a 29-year-old female patient without underlying disease. She experienced subacute onset apathy, aphasia that progressed to mutism, amnesia, psychosis, dyskinesia, consciousness change, and status epilepticus. Antibodies against NMDAR were detected in the patient's serum, plasma, and CSF. Under the diagnosis of anti-NMDAR encephalitis without tumor association, she received immunotherapy from the third week after onset with steroid pulse therapy and plasmapheresis. Initial brain MRI was unspecific. After recovering from status epilepticus and regaining consciousness, the patient underwent FDG-PET/CT scan 9 weeks after onset. The scan revealed occipital hypometabolism including hypometabolism in the primary and associated visual cortices mixed with hypermetabolism at the right lateral temporal and right inferior parietal lobes (Figure , scan 1, and Table ). At that time, cognitive impairment was quantified as 19 points for MMSE and 12 points for MoCA under the background of 18 years of school education. Her symptoms of anti-NMDAR encephalitis kept improving under immunotherapy, including plasma exchange, oral prednisolone, azathioprine, and rituximab. Two months after the first FDG-PET/CT scan, her mRS score was 2, and her cognitive performance was 26 points for MMSE and 27 points for MoCA. The second PET scan exhibited some improvement for occipital hypometabolism but revealed new hypometabolism in the bilateral medial frontal and right anterior cingulate gyrus (Figure , scan 2).


Our case is a 45-year-old white male who was hospitalized to the clinic of infectious diseases, with fever (39°C), myalgia, vomiting, nausea, headache, and abdominal pain. The physical findings included hepatomegaly (19 cm), splenomegaly (16 cm), rash, and conjunctival injection. Eight days before the start of complaints, the patient had been cutting trees in the forest. He did not have a history of traveling to another HFRS endemic area. An acute renal failure was observed in the laboratory tests with an increase of serum creatinine and blood urea nitrogen. Urinalysis shows albuminuria (9.9 gr) and hematuria (35–40 cell/field). Initial total blood count revealed thrombocytopenia (91,000/mm3). Elevations of amylase, lipase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and low serum albumin level were observed as shown in . PCR was 11.4 mg/L. Also, an oliguria (300 ml/day) was present. On the third day of hospitalization, the patient had seizures. He was transferred to the Intensive Care Unit because of his worsening condition. The patient refused to have a lumbar puncture. The unenhanced head CT performed in urgency conditions after seizures showed subcortical bilateral hypodensities within frontal, parietal, and occipital regions (). A head MRI with intravenous contrast showed hyperintensities in affected regions in T2 and FLAIR sequences without diffusion restriction of signal and without microhemorrhages in T2∗ sequences (Figures and ). The radiological consultations considered these pathological images as edematous regions which correspond with posterior reversible encephalopathy syndrome. The electroencephalogram realized found problems related to electrical activity of the brain: “Intermittent bilateral 7-8 Hz slow wave on the left temporal and frontal lobe in a background of low amplitude registration.” HFRS was detected from a blood sample drawn two days after hospitalization, with a positive ELISA test for hantavirus IgM and IgG antibodies. First blood sample showed hantavirus IgM antibody titer 8.2 (0.9–1.1) and IgG antibody titer 6.7 (0.9–1.1). Second blood sample evaluation, after two weeks, showed hantavirus IgM antibody titer 7.1 and IgG antibody titer 6.9. Serological test of Leptospira, HBV (anti-HBc antibody test and HbsAg antigen test), and HCV (anti-HCV antibody test) resulted negative. All the laboratory test results during hospitalization are shown in . Treatment consisted of supportive therapy with ceftriaxone, corticosteroids, antiepileptic, saline infusions, electrolytes, antipyretics, and oxygen therapy. The patient was discharged after 16 days. He underwent another head MRI after 2 months, which resulted normal, without presence of any cerebral hyperintensities (Figures and ).


We present the case of a 75-year-old healthy male patient, who arrived at our Emergency Department for excruciating pain and swelling of the left leg that, when measured, resulted 1,5 times bigger than the right one.
The pain started the day before and worsened during the day, as the diameter of the leg was also increasing. He did not report any previous trauma. The only relevant anamnestic data was a short flight 4 weeks before.
The patient's past medical history was characterized by type II diabetes, hypertension, COPD, and also a nephrotic syndrome, recently diagnosed and still under investigation. His cardiovascular risk factors were cigarette smoking and arterial hypertension.
At the clinical examination, the left leg presented typical signs of phlegmasia cerulea dolens (): distal pulses were not palpable, and the calf was swollen, reddened, and painful, typical for a compartment syndrome.
An urgent angio-CT scan was performed and showed an extensive thrombosis of both renal veins, a hypoplasia of the inferior vena cava () extending from the renal veins to the diaphragm, and a complete thrombosis of the deep venous system of the left leg ().
The venous drainage was partially granted by collaterals, the major being a lumbar vein, which drained into the superior mesenteric vein.
The CT scan also showed a minimal bilateral basilar pulmonary embolism, a mass in the left mammary gland, and also an exceptionally big left inguinal hernia.
We decided to perform an iliofemoral venous thrombectomy associated with an intraoperative phlebography and venous PTA. The phlebography showed thrombotic material in the external iliac vein. The common iliac vein was occluded, determining a retrograde flux in the femoral vein. A thrombectomy with Fogarty catheter was performed, followed by a percutaneous angioplasty with the restoration of an anterograde flux. Due to the presence of good collateral circles, it was not necessary to liberate the renal veins. Because of the presence of a compartment syndrome, a fasciotomy of anterior and lateral compartments was also performed.
Postoperatively, the patient was transferred to the Intensive Care Unit and the clinical evolution was favorable.
At this point, the cause of this massive venous thrombosis had to be found, also considering the presence of a probable breast cancer ().
The thrombophilia screening did not show any pathologic finding. The mammary lesion was on the inferior external quadrant of the left breast with retraction of the superimposed skin. After discussion with the OB/GYN specialist, a tru-cut biopsy was performed. The histopathological examination showed an invasive ductal carcinoma B.R.E. 2 with expression of estrogenic and progestin receptors at 90%, Ki-67 10%, C-erb-2 score 2+. Radical mastectomy was highly recommended, but the patient went back to his original country and we do not know if the operation was actually performed.
The hospital stay was regular, without any complication. A life-long oral anticoagulation with rivaroxaban 15 mg 1/day was started.


A 68-year-old woman presented with a three-week history of upper abdominal discomfort, two episodes of coffee-ground emesis, and passage of dark, tarry stools. She did not take alcohol, non-steroidal anti-inflammatory drugs, or herbal concoctions. She had no history of heartburn, regurgitation, or any problems with swallowing. She had no previous diagnosis of liver disease and no symptoms suggestive of liver disease. Examination revealed an elderly woman, who was in no respiratory distress. She was generally well looking and not pale, also did not have jaundice. Vitals signs were normal. On abdominal examination, there was mild tenderness in the epigastrium; otherwise, it was unremarkable. Rectal examination revealed the presence of black tarry stool. Examination of the cardiovascular, respiratory, and nervous systems was unremarkable. She was mildly anemic with a hemoglobin of 9.2 g/dL, and other laboratory tests were within normal limits. The patient had an upper gastrointestinal endoscopy showing areas of petechial hemorrhage in the stomach. A foreign body (later identified as a 2.5 cm long fishbone) was found in the first part of the duodenum with one end embedded in the wall, and the other end abutting the opposite wall of the duodenum. The free end had produced a 2 cm long ulcer on the opposite wall. This ulcer most likely bled due to peristaltic contractions as the sharp end of the foreign body caused more damage (Figures , ).
Retrieval forceps were used to successfully remove the embedded foreign body. On further questioning, the patient did not remember when she last ate a fish containing meal.


A 27-year-old woman presented to us with a history of chronic plaque psoriasis, which initially started over the scalp with PASI of two but over the next 6 years had gradually involved the elbows and knees and the PASI became 12. She had pitting of her nails, and there was no joint involvement and features of psoriatic arthritis. Her medical history revealed that she was a case of major beta thalassemia/Hb E and she was receiving packed cell infusions every 22 days. She had iron overload related to her disease and her ferritin level was 1256 ng/mL and she was under treatment with 1 g deferoxamine. Previous systemic treatments for her included adalimumab, infliximab, and methotrexate 20 mg weekly for 2 years, which were used individually for disease control. After 2 years of treatment, the disease became nonresponsive to these drugs with gradual progression of the disease severity (Figure A). Her PASI was >10 with Dermatology Life Quality Index (DLQI) > 10 and body surface area (BSA) > 10%. Due to the comorbidity and the unresponsiveness to all other therapies and due to the disease progression, the case was discussed in the rheumatology board. She was started on a combination therapy of adalimumab and infliximab. On starting combination therapy with adalimumab 80 mg SC once, then, after 1 week, 40 mg SC q2wk and infliximab 5 mg/kg IV at 0, 2, and 6 weeks, then q8weeks thereafter, lesions significantly improved initially with reduction in PASI and DLQI but after 6 months the lesions started aggravating and new lesions also started appearing, unexpectedly (Figure B). No side effects appeared. PASI score of 1.6 and DLQI of 1 were increased to 2.4 and 3, respectively, at 24 weeks of treatment. Currently, the patient is under treatment with intralesional suspension of 1% of triamcinolone acetonide subcutaneously, with PASI of 1.2, after the second injection. DLQI and BSA are under two as well.


This is a 31-year-old male who began experiencing focal seizure of deja vu lasting 10-20 seconds about every 2-3 weeks since the age of 14. His first secondary generalized seizure was around the age of 21. He developed focal seizures of receptive and expressive aphasia as many as 5-10 times per day. His seizures remained intractable despite trials of many AEDs (Levetiracetam, Topiramate, Clobazam, Vigabatrin, Lacosamide, Perampanel, Lorazepam, Valium, Alprazolam, and Midazolam). Brain MRI was negative at the age of 24.
The methods to determine the site of ictal onset zone was intracranial EEG monitoring using both strip and depth electrode done in the California Pacific Medical Center (not our facility). A seizure focus was determined to be from multiple sites, including the left temporal language area. Therefore, the patient underwent multiple subpial transection surgery on two separate occasions, as well as the implantation of the RNS at the age of 27. One cortical strip and one depth lead were implanted over the left temporal in California Pacific Medical Center. The care of the patient was then transferred to our facility after the initial titrations.
We adopt the definition of “electrographic seizure” as a sustained rhythmic discharge, including repetitive spiking or spike-and-wave pattern faster than or equal to 2 Hz, with definite evolution in either frequency, location, or morphology. In addition, it should be clearly distinguishable from background, with at least 10 seconds in duration., In this case, the Detection events were mostly composed of nonseizure patterns consisting of epileptiform activities or nondescript patterns. The Long Episode events were also mostly composed of nonseizure patterns, such as brief interictal epileptiform bursts, but also included electrographic seizures (<20% in this case). The events of the Saturation and Magnet sometimes consisted of electrographic seizures.
In the first 2 years after RNS implantation, the neurology team actively programmed the detection and stimulus parameters. The RNS's leads placement and configuration were regarded as optimal at the end of 2 years of programming stage for two reasons. First, on average, the focal seizures of speech disturbances were reduced from 5 times to once a day. However, the frequency of generalized tonic-clonic seizure (GTCS) remained around 3-5 times per year. Second, after reviewing the recorded ECoG data, there were samples of ECoG that demonstrated the abrupt termination of electrographic seizures after initiation of the stimulus, which supports the effectiveness of the stimulus parameters.
Two years after RNS implantation, the neurology team started to focus on the AED optimization because of the remaining GTCS the patient continued to experience. The RNS detection and stimulus settings were held constant to provide reliable ECoG markers in gauging the therapeutic effectiveness of AED changes. The neurology team chose to add Lamotrigine on his current antiepileptic medication regimen (Keppra 4500 mg/daily, Onfi 50 mg/daily, and Vimpat 600 mg/daily), as the patient was not previously prescribed Lamotrigine. The neurology team quickly decided that the Lamotrigine was effective because of the following: (a) The number of Long Episode count decreased (Figure ); (b) From reviewing the ECoG data, including Long Episode, Saturation, and Magnet, the severity and amount of subclinical seizures decreased; (Figures , , , ); and (c) The patient stopped having disabling seizures which were defined as GTCS and noticeable confusion after the Lamotrigine was added.
Although the frequency of disabling seizures subsided after the initiation of Lamotrigine, the neurology team continued increasing this AED in the following 1.5 year based on the ECoG data. With the stepwise increase in Lamotrigine, the severity and number of the subclinical seizures decreased further on ECoG (Figures , , , , ). The serum Lamotrigine level increased to 12.6 μg/mL step by step. The authors believe that controlling these subclinical seizures would both prevent clinical seizures and make the patient ready for the future reduction and/or elimination of other less-effective AEDs.
During this 1.5-year period of drug optimization, the neurology team increased the Lamotrigine stepwise up to 800 mg daily. The patient developed adverse peak-dose diplopia with a higher dose of Lamotrigine (greater than 800 mg) daily. The patient did not have any GTCS since the initiation of Lamotrigine. The Long Episode count showed a decreasing trend during this 1.5-year period despite some fluctuation (Figure ). The need for the patient to utilize Magnet Swipe also decreased. Because of the overwriting of Magnet Swipe data, the count of Magnet Swipe was not available. At the end of this stage, the patient reported that he rarely used Magnet Swipe anymore. The self-reported focal seizures of speech disturbances reduced from once a day to once a week after the initiation of Lamotrigine. Furthermore, the severity and duration of focal seizure decreased, and the patient did not always feel the need to use Magnet Swipe.
In this stage, the neurology team started reducing other AEDs in order to improve the patient's quality of life. The parameter of Long Episode count together with reviewing the ECoG data guided the reduction in AEDs. The goals were to both keep the patient disabling seizure-free and to minimize the adverse effects of polypharmacy by tapering less-effective AEDs. The patient reported both a reduction in sedation and medications, specifically less-effective AEDs. The ECoG parameters and clinical seizures did not increase with the reduction in these less-effective AEDs.
In summary, after 2 years of active RNS programming, the neurology team held the RNS settings constant and focused on optimization of AEDs. The patient was free of disabling seizures for more than one year with the help of the ECoG (Electrocorticographic) data of RNS (Figures , , , , ).


A 40-year-old male, native of Arizona with a past medical history of type 2 diabetes mellitus, hypertension, and obesity developed decreased visual acuity of the left eye. This was sudden in onset and not preceded by trauma or insect bites. He went to see an ophthalmologist, and from there, was referred to a retina specialist for retinal eye exam. There were no associated systemic symptoms at the time. During the retinal exam, he was noted to have a pocket of fluid under the retina, and a diagnosis of central serous retinopathy was entertained. Since this is a self-limiting condition, the patient was counseled and asked to return after one month for a follow-up eye exam.
Over the course of next few weeks, patient's visual symptoms worsened. He developed systemic symptoms of fevers, night sweats, fatigue, and generalized weakness. There was, however, no cough, chest pain, or shortness of breath. Initial blood work revealed positive IgM and IgG serology for coccidioidomycosis. He was started on oral fluconazole and referred to an infectious disease physician. Due to worsening visual symptoms, the patient went back to see his ophthalmologist. On exam, he was noted to have yellowish infiltrates beneath the retina on the left eye extending from the optic nerve to the retinal blood vessels. A diagnosis of chorioretinitis was made (Figures and ). Due to the recent diagnosis of valley fever, it was suspected that his eye involvement may be due to coccidioidomycosis. He was instructed to continue the oral antifungal medication and return for follow-up in a month.
At the initial diagnosis, his complement fixation titer was 1 : 8. He remained compliant with fluconazole. At follow-up visit with his ophthalmologist six weeks after starting antifungal therapy, the retinal inflammation had started to regress (). At his 5 month follow-up visit, there was complete resolution of retinal inflammation with development of scarring (). However, the patient had lost vision from the left eye. Despite resolution of the retinal inflammation, due to proximity to the optic nerve, there was irreversible damage to visual acuity. Over the next few weeks, the patient developed multiple scattered skin lesions, and his fluconazole dose was increased to 800 mg daily.
Unfortunately, repeat complement fixation titer worsened from 1 : 8 to 1 : 16 and then to 1 : 32 on subsequent labs at which point, he was switched to voriconazole 200 mg orally twice a day. He also underwent a spinal tap that was unremarkable. Coccidioides' antibody in the cerebrospinal fluid was negative. A CT scan of the chest showed bilateral pulmonary nodules. Interestingly, he did not have respiratory symptoms. After changing antifungal regimen, the patient had a slow but gradual clinical response with improving titers, resolution of fevers, night sweats, and skin lesions.


A 71-year-old Japanese man presented to our hospital with a chief complaint of urinary retention. He had chronic obstructive pulmonary disease, hypertension, and a history of left femoral head replacement due to osteoarthritis of the hip. Additionally, he had a history of alcohol consumption and cigarette smoking. Prostate volume of 42 cm3 was defined using transabdominal ultrasonography. Urinary catheterization was performed, and alpha-blocker treatment was initiated. A follow-up examination conducted 1 month later showed serum prostate-specific antigen (PSA) levels of 74 ng/mL, although the last PSA test performed a year ago had revealed normal PSA levels. Blood and urine test results were nearly within normal limits, except that mild anemia and mild hypoalbuminemia were noted. Prostate tissue samples were obtained via transrectal needle biopsy. Digital rectal examination revealed a firm prostate; however, a prostate tissue sample stained with hematoxylin and eosin showed inflammation but no malignant cells. One month after the first biopsy, urinary retention recurred, but 2 weeks of clean intermittent self-catheterization improved the obstructive symptoms. One month later, the patient had elevated PSA levels of 180 ng/mL, and a second prostate biopsy was performed . Adenocarcinoma (Gleason score 5 + 4) was detected in 1/12 needle cores . Computed tomography revealed pelvic lymph node swelling, and multiple bone metastases (lumbar spine, pubic bone, and left acetabulum) were detected using bone scintigraphy; therefore, the patient was diagnosed with stage 4 prostate cancer. Moreover, we detected abundant plasma cell infiltration with periglandular storiform fibrosis in prostate tissue samples Figures and . Although plasma cell clonality was not detected, IgG4 immunochemical staining demonstrated IgG4-positive plasma cells Figures and . The ratio of IgG4-positive/IgG-positive plasma cells was >50% . Given the result of the second biopsy, the initial prostate biopsies were reviewed again, and large numbers of IgG4-positive plasma cells were observed. At this point, the serum IgG4 levels were 1310 mg/dL (normal: <117 mg/dL), and a diagnosis of simultaneous IgG4-related prostatitis and prostate cancer was made. The patient immediately received combined androgen blockade treatment, and his serum PSA levels decreased to 1.7 ng/mL for 4 months. However, he developed castration resistance after 8 months of hormone therapy. Although abiraterone, docetaxel, and cabazitaxel were administered, cancer progressed, and multiple liver metastases appeared. He died 24 months after the diagnosis of prostate cancer. No treatment was given for IgG4-related prostatitis as the patient could urinate without a catheter at the time of diagnosis confirmation. The serum IgG4 levels slightly decreased to 883 mg/dL in the 7th month of hormonal therapy and returned to normal when prednisolone at a dose of 10 mg/day was coadministered with abiraterone in the following month. Notably, he never complained of urinary retention until death.


An 88-year-old female was admitted to our medical intensive care unit with a two-day history of worsening dyspnea and hypotension. An initial assessment at the time of admission ruled out pulmonary embolism. On further inquiry, the patient had a history of consistent, unremitting, high-grade fever (100°F) for the past week. It was also noted that her dyspnea developed after the onset of high-grade fever. Additionally, she had also developed a mildly productive cough during the past week. Her past medical history was significant for long-standing uncontrolled diabetes and end-stage renal disease. Family members of the patient declined any history of bird exposure at home or as part of her occupation. Social history revealed that she was a non-smoker and non-alcoholic. Furthermore, she did not have any history of illicit drug abuse.
A few hours after her admission, her condition began to deteriorate. Her oxygen saturation dropped from 89% to 70%. She became severely dyspneic with a raised blood PaCO2 level. Based on the rapid clinical decline, the decision was taken to electively intubate her and further proceed with treatment on the grounds of sepsis. On physical examination, she was febrile (100°F), with blood pressure 80/50 mmHg and pulse 88 beats/min. Respiratory system examination was significant for bilateral basal crepitations with an expiratory wheeze. Chest x-ray revealed patchy areas of alveolar opacification in bilateral lung fields. Opacification predominantly involved the right upper and middle lung fields and left upper and lower lung fields. The diseased regions in the right lung zones collapsed to form a non-homogeneous wedge-shaped area of opacification with internal air bronchograms (Figure ). Furthermore, physiological calcification of aortic knuckle was also evident. Based on the chest x-ray findings, a preliminary diagnosis of pneumonia was made.
An echocardiogram revealed no obvious clots in the left ventricle. However, it was significant for mobile vegetations on the non-coronary cusp of the aortic valve (Figure ). A grade I diastolic dysfunction with a global ejection fraction of 58% was also noted.
On the second day of admission, she suffered from a higher fever spike (102°F). This bout of fever was accompanied by leukocytosis (total leukocyte count 26.8 x 109/L with a neutrophil count of 92%). The patient was started on broad-spectrum antibiotics vancomycin and cefepime. Subsequently, the result of cough sputum culture was negative. However, blood culture was positive with Klebsiella pneumoniae species which was only susceptible to colistin. The antibiotic was changed to colistin and was continued for 10 days. Thereafter, her clinical condition improved. Follow-up echocardiography was scheduled upon discharge to monitor the resolution of the vegetations.


Patient 1. A 21-year-old female with weakness of the neck and limb muscles and dyspnea was admitted to our hospital (). Her symptoms rapidly progressed to myasthenic crisis and she was treated with plasma exchange. In addition, she had adverse reactions to drugs including hepatotoxicity induced by calcineurin inhibitors and leukocytopenia induced by IVIg. Thus, her treatment choice was limited to prednisolone and plasma exchange. After an internal shunt was created in her right forearm, she underwent two sessions of plasma exchange every 3 weeks to avoid myasthenic crisis. Eculizumab treatment was started with add on 30 mg/day of prednisolone. During the following 6 months, her symptoms gradually improved. Her QMG score was 26, which was greatly improved from her worst score of 36. She has residual weakness, however, she does not use a wheelchair. She can walk with no assistance and gains employment at a movie company.


Patient 2. A 21-year-old female with a 4-year history of MG was referred to our hospital. A hyperplastic thymus was removed at the age of 17 years. She required oral prednisolone, tacrolimus and IVIg for the maintenance treatment. At the ages of 22 and 23 years, she experienced myasthenic crises and received immunoadsorption using a tryptophan column. Soon after being weaned from the mechanical ventilation, she started eculizumab treatment. During the follow-up of 12 months, she did not fall into a myasthenic crisis. Her QMG score was 16, which was greatly improved from her worst score of 28. As she has a nasal voice, other immunosuppressive treatment may be required; however, she works part-time at a convenience store and enjoys traveling with her friends.


We report the case of a 9-year-old boy who was referred to the pneumonology, allergology, and clinical immunology unit of the Poznan Pediatric University Hospital because of pneumonia, bilateral otitis media, and vesicular dermatitis.
Since the age of 2 years, he suffered from recurrent respiratory tract infections and required multiple hospitalizations because of recurrent bronchitis and pneumonia, maxillary sinusitis, otitis media, purulent dermatitis with Pseudomonas aeruginosa and Staphylococcus aureus infection, and severe varicella complicated by pneumonia, sinusitis, and gastrointestinal infection. He completed a full course of vaccinations, including BCG (Bacille Calmette–Guerin) and MMR (measles–mumps–rubella) vaccines without adverse effects following immunization (AEFI). The family history was complicated by multiple sclerosis in the patient's father.
He presented with neurodevelopmental delay and dysmorphic features with oblique palpebral fissures and eyebrows, retrognathia, low set small auricles with thick helices, and clinodactyly of the V fingers. The erythematous papulovesicular rash was present on the skin of the face, in the perioral region, and in the retroauricular area. In the nasopharynx and in the oral cavity, inflammatory lesions were observed. The most striking symptom was lymphadenopathy with numerous bilaterally enlarged cervical and submandibular lymph nodes. During hospitalization, he required antibiotic therapy, bilateral paracenthesis with tympanostomy, and drainage of maxillary sinuses. Laboratory evaluation revealed an antibody production defect and a memory B cell deficiency. Therefore, replacement therapy with intravenous immunoglobulin (IVIg) was initiated, and further genetic testing was recommended. The patient received three IVIg transfusions in monthly intervals, but afterward the parents decided to discontinue the therapy, and the boy was lost to follow-up.
At the age of 11 years, the boy was referred again to our clinic because of recurrent fevers, accompanied by vomiting, abdominal pain, cervical lymphadenopathy, and splenomegaly. The episodes of fever started 5 months before the hospitalization; they were not associated with any signs and symptoms of infection, they would reach 39.5 degrees, and did not respond to treatment with antibiotics. At that time, no other family members were ill, the boy had no contact with any toxic substances or infections, and he did not travel to the Mediterranean or exotic regions.
The laboratory tests showed pancytopenia, lymphopenia and neutropenia, high inflammatory markers, hypoalbuminemia, IgG and IgM hypoimmunoglobulinemia, hyperferritinemia, hypertriglyceridemia, hypertransaminasemia, and positive EBV-DNA (93,400 copies/ml) in the peripheral blood. Further laboratory findings comprised a markedly elevated (7,255 U/ml) serum concentration of the soluble interleukin 2 receptor (sIL-2R, sCD25) and a decreased intracellular expression of perforin (CD107a) on NK cells and increased on CD8+ T cells. Concomitantly, neither in the bone marrow nor in the lymph node were signs of hemophagocytosis found. Hence, seven of the eight diagnostic criteria (four clinical and three immunological criteria) of hemophagocytic lymphohistiocytosis (HLH) were fulfilled () (data displayed in ).
With the concern of severe respiratory infection () and sepsis in an immunocompromised patient, initial empiric pharmacotherapy was based on broad spectrum antibiotics meropenem and vancomycin, Pneumocystis jiroveci prophylaxis with cotrimoxazole, and antiviral and antimycotic medications acyclovir and fluconazole. The chemo-immunotherapy for HLH was initiated with methylprednisolone pulse therapy, etoposide, and cyclosporine. The boy also required supplemental transfusions of albumins, immunoglobulins, prothrombin complex, and red blood cell preparations. The initial response to the therapy was satisfactory with an improvement in the patient's general state, a resolution of fevers, and a decrease in the serum inflammatory markers. Subsequently, however, the boy's state deteriorated, febrile episodes returned, and exacerbation of the supraclavicular and abdominal lymphadenopathy was observed (). Based on complex diagnostic procedures including histopathology, immunology, and magnetic resonance imaging (MRI), the diagnosis of IV stage nodular sclerosis (NS) Hodgkin's lymphoma was established. The boy underwent successful chemotherapy based on the Euronet Pediatric Hodgkin's Lymphoma protocol (EuroNet-PHL-C1) including OEPA (vincristine, etoposide, prednisone, and doxorubicin) followed by 18-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) reevaluation. Further considerations and decisions regarding therapeutic options, including bone marrow transplantation, are ongoing.


A 50-year-old Chinese male presented with bilateral blurred vision for 3 months. Nine months earlier, he experienced pulmonary embolism and lower limb venous thrombosis, and was diagnosed with antiphospholipid antibody syndrome (APS). He had lost 10 kilograms in the past 9 months. No other gastric or constitutive symptoms were reported.
On examination, his best corrected visual acuity (BCVA) was 20/200 OU. Anterior chamber was basically normal except for moderate cataract in both eyes. Fundus examination showed bilateral diffuse oval yellow patches in the posterior pole (Fig. a and b, top left), corresponding to a classical giraffe sign, namely hypo-fluorescence in autofluorescence (AF, Fig. a and b, top middle) and hyper-fluorescence in the early and late phases of fundus fluorescein angiography (FFA, Fig. a and b, top right) and indocyanine green angiography (ICGA) (Fig. a and b, bottom middle), with late phase pinpoint leakage. Spectral domain optical coherence tomography (SD-OCT, Fig. a and b, bottom right) B-scan well-depicted a mosaic pattern of RPE alterations between irregular thickening and atrophy. Blocked fluorescence on ICGA due to choroidal lesions was also noticed (Fig. a and b, white arrows). Based on these typical findings, the patient was diagnosed with BDUMP, and malignancy screening was strongly recommended.
Blood tumor markers reported as: CA19–9795.0 U/ml, CA125 3770.0 U/ml, Cyfra 211 57.6 ng/ml, CA242 > 150.000 U/ml, NSE 46.1 ng/ml. 18F- fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) (Fig. c) showed an FDG-avid lesion in the gastric antrum (Fig. c, big arrow), and multiple hypermetabolic lymph nodes (Fig. c, small arrows) were also noted in perigastric, retroperitoneal, mediastinal and left supraclavicular region, suggestive of gastric malignancy with distant lymph node metastasis. Based on these findings, gastroscopy was ordered. Pathological diagnosis (Fig. d) reported as poorly differentiated adenocarcinoma. The patient was finally diagnosed with BDUMP and secondary APS due to gastric adenocarcinoma. Systemic chemotherapy was suggested, but after evaluation, the patient’s systemic condition was too poor to tolerate any chemotherapy. After consideration, the patient chose palliative care out of the late stage and unresectable nature of the malignancy and economic reasons.


A 49-year-old Sri Lankan man with a history of long standing type 2 diabetes mellitus and hypertension, presented with fever, loss of appetite and generalised body aches for 1 week duration. He had a past history of right medial malleolar screw fixation 10 years ago following a traumatic uncomplicated closed fracture. He was diagnosed with type 2 diabetes mellitus 20 years ago; however, he was lost to follow-up with poor glycaemic control demonstrated by a HbA1c on admission of 8.5%. He was a non-smoker and consumed alcohol occasionally. He did not have any history of chronic lung disease or steroid use. There was no recent history of trauma or break in skin integrity and there were no cutaneous lesions or ulcers evident on examination. However, he was a tractor driver and had a history of exposure to mud in paddy fields. Due to the presence of fever with considerable myalgia and exposure to mud in paddy fields, he was initially suspected to have leptospirosis and was started on intravenous ceftriaxone at the local hospital. Four days later, he developed right ankle swelling and discolouration and was transferred to the tertiary care centre for further management.
On admission, he was febrile (103 °F) and tachycardic with a pulse rate of 104 / min. His other haemodynamic parameters were normal with a blood pressure of 140/80 mmHg and was mildly dehydrated with a urine output of 0.5 ml/kg/hour. He was not haemodynamically compromised due to sepsis and his urine output improved with fluid resuscitation. He had a white blood cell count of 15 × 103/uL with a neutrophil leucocytosis; C-reactive protein was 190 mg/dl and erythrocyte sedimentation rate was 86 mm/hour. His platelet count was 148 × 103/uL. His liver enzymes were mildly elevated and rest of the basic biochemistry was unremarkable (alanine transaminase: 252 U/L, aspartate transaminase: 222 U/L, serum creatine: 0.46 mg/dl). The X-ray of the right ankle revealed a healed fracture with two screws which were in position. There was no evidence of osteomyelitis (Fig. ).
He underwent a wound debridement of the right ankle and the necrotic skin and subcutaneous tissue were excised. The pus collection in the subcutaneous tissue plane was removed. Aspiration of the ankle joint revealed purulent fluid. Therefore, an arthrotomy and washout was done. One loosely fitted screw was removed and the wound was left open. Removal of the second screw was considered but this procedure was abandoned due to technical difficulties and concern about iatrogenically causing a fracture in the process.
The pus culture and the peripheral blood culture was positive for Burkholderia pseudomallei sensitive to meropenem and co-trimoxazole. Direct smear showed gram-negative bacilli with bipolar appearance. Non-lactose fermenting colonies with a metallic sheen were isolated on blood and MacConkey agar, and Burkholderia pseudomallei species were isolated using the latex agglutination test (Fig. ). The BD PHOENIX (Becton Dickinson Diagnostic Systems, Sparks, Md.) automated microbiology system for direct identification also confirmed the presence of Burkholderia pseudomallei.
His melioidosis antibody titre using the indirect haemagglutination assay was > 10,240. He was empirically managed with intravenous ceftriaxone 1 g 12 hourly and metronidazole 500 mg 8 hourly for 7 days. This was because Leptospirosis or anaerobic infection of the lower limb was thought possible given his environmental exposure history. Following the bacterial culture reports and the antibiotic sensitivity patterns, a diagnosis of melioidosis was made and the antibiotics were changed to intravenous Meropenem 1 g 8 hourly and Metronidazole 500 mg 8 hourly. Metronidazole was continued due to the presence of necrotic tissue and suspicion of superadded anaerobic infection. However, after 1 week he clinically deteriorated with worsening wound infection, fever and septic shock. He was resuscitated with fluids and commenced on noradrenaline. He required inotropic support for 4 days. He underwent another wound debridement and the dose of intravenous Meropenem was escalated to 2 g 8 hourly while continuing intravenous Metronidazole 500 mg 8 hourly and oral Co-trimoxazole 1920 mg 12 hourly was also added. He improved after a few days following the second wound debridement and supportive management. Fortunately, he did not develop any other organ dysfunction. All three antibiotics were continued for a period of 8 weeks.
He was screened for other foci for infection with chest radiograph, transthoracic and trans-oesophageal echocardiogram, abdominal ultrasonography and urine culture and all were negative. A computed tomography of the chest and abdomen was not performed as he did not have any clinical features to suggest a chest or abdominal foci of infection and the basic imaging were negative.
His temperature normalised 4 days after the second wound debridement and escalation of antibiotic therapy. However, he further required repeated wound debridement and removal of necrotic and infected tissue. His inflammatory markers became normal after 5 weeks of antibiotics (C-reactive protein of 2.6 mg/dl). Wound healing with secondary intention was achieved after 6 weeks (Fig. ). He was given a total course of intravenous antibiotics for 8 weeks and was discharged on oral co-trimoxazole 1920 mg 12 hourly. Repeat X-rays at 2 months showed features of chronic osteomyelitis (Fig. ). Due to the high risk of recurrence, the eradication phase was continued for a period of 6 months.
At 6 months follow up, he had satisfactory functional outcome with acceptable range of motion. There was no clinical evidence of relapse. However, the plain radiographic changes were persistent without any worsening.


A 10-year-old girl presented to the ophthalmology department with a fast-growing salmon-colored mass protruding from the medial aspect of the right lower eyelid for approximately 1 month (). The orbital lesion was also demonstrated on magnetic resonance imaging (MRI) () and excisional biopsy of the mass was performed. Histopathological examination revealed B-cell MZL ().
Upon diagnosis, the patient was referred to the pediatric oncology department. On physical examination, lymphadenopathy and hepatosplenomegaly were not detected. The metastatic workup including hemogram, biochemistry tests, immunoglobulins, brain MRI, cerebrospinal fluid cytology, and bone marrow study were within normal limits. Autoantibody tests were negative. Helicobacter pylori, Chlamydia psittaci, and Chlamydia trachomatis antibodies were negative. Conjunctival smear was unremarkable. The patient did not have any history of conjunctivitis or exposure to birds. Apart from the lesion in the right eye, no other pathological involvement was detected in PET-CT. The patient was graded as T1bN0M0 according to AJCC and as Stage 1 according to Ann Arbor staging.
As repeated ophthalmological examinations revealed bilateral suspicious follicular reaction, Chlamydia was assumed and antimicrobial treatment (doxycycline, 200 mg/day) was initiated. After 2 weeks of treatment, progression of the tumor was observed, and external radiotherapy was planned immediately. The prescribed dose was 36 Gy in 17 fractions to the isocenter (1.8 Gy/fraction dose) using 6 MeV electrons. Cerrobend block was created to protect the lens. Radiotherapy resulted in rapid remission. The child is currently in remission for 26 months. The patient’s mother consented to all treatments and publication of this article.


A 51-year-old asymptomatic man, with no history of hematuria, underwent to a routine US. The exam demonstrated a bladder with regular walls, except for an area of focal thickening and a nodular lesion in the bladder floor, close to the right ureteral meatus (). Serum and urinary laboratory tests were normal.
Cystoscopy found three elevated lesions in the right lateral vesical wall, each one with about 0.5cm, all of which with intact mucosa. Additionally, there was an ipsilateral ulcerated peri-meatal lesion (). All lesions were cold-cup biopsied and the pathological analysis revealed deposition of an eosinophilic proteinaceous substance throughout the mucosa and around the vessels. This was also associated with a mixed inflammatory process at the lamina propria, without evidence of cellular atypia ( and ). The search for infectious agents and amyloid protein (red-congo) were negative. The findings led to the diagnosis of Tamm-Horsfall protein deposition (THP). The patient remained asymptomatic and had no complications following the procedure.


A 67-year-old Chinese diabetic and hypertensive female patient presented with sudden onset vertigo with nausea and vomiting 4 days ago. Then she presented with sudden onset of right hemiparesis 2 days ago and developed rapidly quadriplegia (upper and lower limbs with grade 0 power), dysarthria, bilateral facial weakness. Her eyes moved normally and no diplopia. She had no history of smoking or drinking. On physical examination, the temperature was 36.8 °C, the pulse 76 beats per minute, and the blood pressure 165/95 mmHg. Detailed neurological examinations revealed quadriplegia, dysarthria, bilateral facial weakness, bilateral positive Babinski’s sign. The pupils were equal and reactive. Corneal reflexes were present and there was no gaze palsy and nystagmus, scoring 24 on the National Institute of Health Stroke Scale (NIHSS). On admission, laboratory findings indicated she had abnormal fasting blood sugar, HbA1c, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), uric acid. Detailed results were shown in Table . Twenty four hours Holter electrocardiography showed sinus rhythm without ST-T segment change and occasional premature atrial contractions (22 times within 24 h). Echocardiography showed mild mitral valve regurgitation and the left ventricular ejection fraction was 68%. Color Doppler flow imaging examination showed a mild resistance index of the intracranial segment of the vertebral artery (VA) and BA.
Cranial magnetic resonance imaging (MRI) brain diffusion-weighted imaging at 3.0 T revealed a giant heart-shaped hyperintensity area (“heart appearance-like sign”) on both sides in the ventral ponto-medullary junction [Fig. ]. Abnormal signal was observed in the same region by T1, T2, fluid-attenuated inversion recovery and apparent diffusion coefficient (ADC). On the basis of these findings, the patient was diagnosed to be having an acute bilateral ponto-medullary junction infarction. Next, we executed the detection of whole brain digital subtraction angiography (DSA) for the patient and DSA showed the basilar artery and vertebral artery remained intact [Fig. ]. Therefore, we speculated that the bilateral ponto-medullary junction infarction might be caused by the deep perforating branch of the basilar artery. The patient was treated with Aspirin (100 mg/d) and rehabilitation was initiated. Six months later, the patient still had quadriplegia (upper and lower limbs with grade 2 power), dysarthria, bilateral facial weakness and nasal feeding.


The individual who tested positive was an Italian man in his late 20s, in healthy condition. He was in Wuhan from 20 January to 3 February to visit his Chinese friends. He had no exposure to marketplaces, live animals, known sick people or access to healthcare facilities. In order to avoid SARS-CoV-2 infection, he stayed at home except for a 1-day walk in the town district. His close contacts were the three members of the Chinese family hosting him, who are still in healthy condition.
On 6 February, the case was admitted to the Isolation Unit of the National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ for isolation and clinical assessment, with a transient mild conjunctivitis and a body temperature of 37.3 °C. Laboratory findings were all within normal values and common respiratory pathogens (influenzavirus A and B, parainfluenza virus, respiratory syncytial virus, rhinovirus, adenovirus, enterovirus, metapneumovirus, bocavirus, coronavirus strains HKU1, NL63, 229E and OC43, Bordetella pertussis, Mycoplasma pneumoniae and Legionella pneumophila) on pharyngeal swab were excluded. At admission, a second positive real-time RT-PCR on a nasopharyngeal swab confirmed the COVID-19 diagnosis. As the patient was paucisymptomatic, we retrospectively tested serum samples collected at admission using in house-prepared immunofluorescence (IF) slides and neutralisation test as confirmatory test. The IF results showed positivity for both IgG and IgM (≥ 1:640 and 1:80, respectively) at the same time point of the first viral RNA positive result. A preliminary evaluation of the IF test was performed using residual negative samples and few serum samples positive for other human coronaviruses. Two chest computed tomography (CT) scans of the patient (on 7 and 17 February) were normal.
On 7 February, off-label oral treatment with lopinavir/ritonavir (400/100 mg every 12 h) was started after obtaining written informed consent []. SARS-CoV-2 RNA in stools, nasopharyngeal and oropharyngeal swabs resulted positive at different time points, whereas urine, spermatic fluid, saliva, blood and conjunctival swabs were persistently negative ().
On 12 and 13 February, two nasopharyngeal swabs resulted negative for SARS-CoV-2 RNA. Nevertheless, on 14 February, a transient whitish exudate on the right palatal tonsil was observed and the oropharyngeal swabs were negative for bacterial growth and again positive for SARS-CoV-2 RNA. No other laboratory finding was remarkable. The exudate disappeared within 48 h.
On 22 February, the patient continued to be asymptomatic and afebrile; the isolation regimen was stopped and the patient discharged.
No other COVID–19 case was observed in the 55 Italian citizens at quarantine. They were discharged at the end of 14-day quarantine after obtaining two SARS-CoV-2 negative samples 24 hours apart near or on the completion of the period.


An 11-week-old female ex-premature infant (corrected gestational age 6 weeks) presented to a peripheral hospital with respiratory distress and a three-day history of cyanotic episodes, following three weeks of upper respiratory tract infection symptoms. The infant was born at 35 weeks' gestation, weighing 2489 g, and did not require resuscitation or respiratory support at birth. The newborn had a 5-day admission to the special care unit for feeding establishment and observation prior to being discharged home well on day 7 of life. The child's mother had received six cycles of R-CHOP for NHL between 17 and 33 weeks of gestation.
The infant was tachypneic and hypoxic, was commenced on high flow nasal cannula support, intravenous (IV) ampicillin and gentamicin, and managed at the peripheral hospital's critical care unit. Over the next two days, respiratory support was escalated to noninvasive ventilation, and antibiotics were changed to IV cefotaxime (D1–D8) and IV azithromycin (D3–D5).
Nasopharyngeal aspirate (NPA) was negative for eight respiratory viruses. Respiratory virus detection for influenza A, influenza B, parainfluenza 1, 2, and 3, respiratory syncytial virus (RSV), and adenovirus was performed using an in-house respiratory virus multiplex real-time RT-PCR assay [], while human metapneumovirus (HMPV) was tested with the in-house real-time RT-PCR assay utilising oligonucleotides []. Testing for Pneumocystis jirovecii was also requested on the NPA specimen and performed using an in-house real-time RT-PCR assay []. A synthetic reference standard was also utilised to enable quantification. Human immunodeficiency virus (HIV) serology was negative. A chest X-ray revealed diffuse bilateral ground glass changes ().
As the hypoxic respiratory failure worsened, atypical infections and possible childhood interstitial lung disease (ChILD) were considered and pulse IV methylprednisolone was commenced. The NPA was subsequently positive for Pneumocystis jirovecii DNA at 2.0 × 106 copies/mL. Oral co-trimoxazole 20 mg/kg/day (D4) was commenced and transitioned to IV co-trimoxazole (D8) due to clinical deterioration.
On day 9, the infant developed a left pneumothorax and pneumomediastinum, requiring intercostal drainage. The child was intubated, ventilated, and retrieved to our Pediatric Intensive Care Unit (PICU) due to worsening respiratory failure. In addition to IV co-trimoxazole, IV lincomycin and primaquine were commenced as second-line PCP therapy due to the clinical deterioration [], and antimicrobial cover was broadened to IV piperacillin-tazobactam.
Steroids were weaned over the next 10 days (D4–D14). All other microbiological and virological testing were negative. The immune screen revealed mild pan lymphocytopenia, severe hypogammaglobulinemia, and neutropenia, suggestive of a combined immunodeficiency (). The infant was commenced on fungal (fluconazole) and viral (valaciclovir) prophylaxis as well as immunoglobulin replacement therapy (IRT) and intravenous immunoglobulin (IVIg) at 0.4 g/kg. Granulocyte-colony stimulating factor (G-CSF) was also administered.
The patient's respiratory failure continued to worsen, and the infant subsequently developed acute respiratory distress syndrome (ARDS). An attempt at high-frequency oscillatory ventilation was ineffective. The infant was then placed on VV-ECMO on day 15 of the presentation. Bronchoscopy performed on day 16 was still positive for Pneumocystis jirovecii DNA at 1.6 × 105 copies/mL.
From day 40 (24 days after commencement of VV-ECMO) until day 42, the infant received three doses of poractant alfa (Curosurf) via the endotracheal tube. The patient was also commenced on IV hydrocortisone (1 mg/kg 6 hourly) on day 41, which was slowly weaned off over a two-week period. The child was successfully decannulated to conventional ventilation (D46) and extubated on day 53. Subsequent immunological assessment revealed adequate lymphoproliferation responses to phytohemagglutinin (PHA) and adequate levels of recent thymic emigrants. The lymphocyte counts slowly normalised, confirming a secondary combined immune deficiency.
The infant improved clinically, was stepped down to oral antimicrobials, and was discharged home on day 103 with supplemental oxygen. The patient remained on supplementary oxygen at home, IRT, and antimicrobial prophylaxis including oral valaciclovir, fluconazole, and co-trimoxazole until the age of 6 months. The timeline of events is summarised in . The infant's mother remained well throughout and did not have any investigations for Pneumocystis jirovecii. Informed consent was obtained from the infant's parent for this case report.


An 89-year-old male was referred to our department for an evaluation of prolonged cough from a physician after screening tests. The patient's past medical history revealed presence of hypertension, subdural hematoma, and lumber canal stenosis. The patient had no history of intraoral trauma.
When we examined the patient's oral cavity and pharynx, the patient furiously coughed and expectorated a small mass. The mass was approximately 10 mm in diameter and was covered with normal mucosa (). We only observed mild bleeding on the base of the tongue by fiberoptic examination, but there were no other abnormal findings in the patient's oral cavity, pharynx, and larynx. We confirmed the well-defined, rounded, high-density mass with a tiny pedicle on the base of the tongue in prior cervical spine computed tomography (CT) images taken by the orthopedic department 6 months before the patient's first visit to our department (). His chronic cough persisted even after removal of the mass. According to the upper gastrointestinal endoscopy results, we concluded that the patient's cough was due to gastroesophageal reflux disease.
Histological examination revealed that the mass consisted of circumscribed bone, and it was surrounded by benign-appearing stratified squamous epithelium (). The bone tissue had lamellar structures. There was no evidence of malignancy in the specimen, and the histological diagnosis of an osseous choristoma was made. There were no signs of recurrence at the time of follow-up examination 15 months later. Written informed consent was obtained from this patient.


Our patient was a 48-year-old African American female with a history of sarcoidosis, depression, and vitamin D deficiency. Her sarcoidosis was initially diagnosed by bronchoscopy and endobronchial ultrasound-guided biopsy after the patient was found to have incidental pulmonary nodules about six years prior to this presentation. She had been treated with systemic steroids and methotrexate, and had been stable off medications for one year prior to presentation. During a routine healthcare visit, she reported new onset of nausea and heartburn for one month. She was started on pantoprazole 40 mg daily, which only slightly improved her symptoms. In view of her systemic disease and advanced age, she was referred for an esophagogastroduodenoscopy, which showed Los Angeles classification grade A esophagitis of the gastroesophageal junction (Figure ) and erosive gastritis of the antrum and body (Figures , ).
Biopsies of gastric antrum and body showed severe active chronic gastritis with non-necrotizing granulomatous inflammation (Figure ), with negative staining for fungi, Helicobacter pylori (Figure ), and mycobacteria (Figure ). These findings were consistent with a diagnosis of gastric sarcoidosis.
The patient resumed treatment with steroids and improved symptomatically, and she is now being followed outpatient.