A 70-year-old male patient was admitted to Internal Medicine Department at the Hippokrateion University Hospital, due to fever up to 39°C for 3 days, accompanied by confusion and disorientation within the last 24 hours. His past medical history included benign prostatic hyperplasia, beta thalassaemia trait and cholecystectomy. A missionary trip to Madagascar was described 8 months prior to the present hospitalization.
The patient had several admissions in different hospitals over the last 8 weeks due to high fever ranging between 38–39°C, associated with recurrent temporal headaches and episodes of transient ischemic attacks presented as hemiparesis, dysarthria, mouth dropping and transient numbness of the right upper limb which were resolving within hours. On the basis of negative blood cultures on several occasions, unresponsiveness to antibiotics, extremely elevated inflammatory markers (Erythrocyte Sedimentation Rate [ESR]=65mm/h, C-reactive protein [CRP]=102mg/L) and a highly suspicious magnetic resonance angiography indicating potential inflammatory stenosis of right vertebral artery and left common carotid artery, the patient was diagnosed with temporal arteritis and treated with IV steroids. Of note, temporal artery biopsy was negative, repetitive computed tomography (CT) scans of the brain did not reveal any abnormality. Following the first course of IV steroids, the patient considerably improved on both clinical and biochemical grounds (ESR=25mm/h, CRP=3,7mg/L). Blood investigations performed over this period are summarized in .
Particularly in view of immunology, ANA was weakly positive with titre 1/80 ds-DNA, p- and c- ANCA, rheumatoid factor and anti-CCP antibodies were negative. Serum immunoglobulin and complement tests were normal.
At that point, two weeks after discharge, the patient was admitted to our ward on treatment with prednisolone 60mg daily, methotrexate 20mg/week, clopidogrel 75mg daily and folic acid 5mg/week. On admission he had stable vital signs (B.P=130/90mmHg, HR=92 bmp, SpO2=96%, Temperature=37,5°C), he was fully disoriented and the clinical examination revealed nothing significant. A CT scan of the brain without IV contrast substances showed only a mild asymmetry of the subarachnoid spaces on the frontal lobe. Despite of the high index of clinical suspicion for CNS infection, we were unable to perform a lumbar puncture because of ongoing treatment with clopidogrel. Clopidogrel and methotrexate were discontinued and corticosteroids were reduced to 30mg daily. The initial laboratory tests showed WBC at 13.500 (88% neutrophils), CRP at 80mg/dl (normal values <6 mg/dl), and ESR at 45mm/hr. Differential diagnosis included CNS infection, and/or treatment-resistant autoimmune disease.
After being consulted by the Infections Department, the patient was started on iv intravenous antibiotics and antiviral regimens: Ceftriaxone 2gr bid, Acyclovir 750mg qid, amikacin 1gr, Linezolide 600mg bid, Voriconazole 400mg bid.
A brain MRI with gadolinium was performed and the radiologist’s official report was as follows: 3 lesions (max diameter 1,3cm) close to the corpus callosum, 2 of them on the right of the midline and 1 on the left, with perifocal cerebral oedema, constriction in the diffusion-weighted sequence and mild ring-shaped enhancement in the right posterior lesion. Two smaller lesions with mild perifocal oedema and peripheral enhancement adjacent to the frontal horn were also reported (). These findings were strongly indicative of possible abscesses or aspergillus infection. Electroencephalography study was totally normal.
Lumbar puncture was performed and cerebrospinal fluid’s (CSF) chemical profile demonstrated glucose levels at 70mg/dl (normal values 50–80mg/dl or 60–80% of blood glucose), LDH at 34 U/L (normal values 7–30 U/L), and protein at 86mg/dl (normal values 15–45mg/dl). Cellular CSF analysis revealed pleocytosis with WBC count at 60/mm3 (normal values up to 5cells/mm3), lymphocytes predominance and Gram-positive coccus. A multiplex Real-Time polymerase chain reaction of CSF confirmed infection due to Listeria monocytogenes, sensitive to resolution of gastrointestinal symptoms.
With regards to the overall condition the patient remained afebrile and all of his symptoms subsided after completing 6 weeks of intravenous treatment with ampicillin. A new brain MRI revealed significant improvement ().
He was discharged on the 50th day with the following instructions: levetiracetam 1,5gr/d, prednisolone 15mg q.d.
At the follow-up appointment one month later, his laboratory tests were totally normal, he was in excellent clinical condition and he had started tapering corticosteroids. Eight months after discharge, he is fit, prednisolone treatment has weaned off to 2,5mg on alternate days without any reappearance of fever and headaches, and inflammatory markers are entirely normal ().


On March 11, 2020, a 68-year-old woman attended the Tianjin Taida Hospital surgical Clinic mainly because of intermittent cough for > 1 month. She had a 2-year history of hypertension controlled by medication, and no history of smoking or alcohol consumption. She had an intermittent cough with white sticky sputum, without any other symptoms or signs. On the same day, the patient was referred to the Fifth Central Hospital of Tianjin. Here vital signs were: body temperature 36.2 °C, pulse 86 beats/min, respiration rate 18 breaths/min, blood pressure 142/85 mmHg, and she was fully conscious. There was no visible enlargement of her superficial lymph nodes. She had no cyanosis, percussion pain in the sternum, or abnormal respiratory movements. She had coarse breath sounds in both lungs, no pleural friction sounds, and audible inspiratory crackles in the left lung. Heart sounds were strong and regular, with no pathological murmurs in any valve auscultation area. Carcinoembryonic antigen (CEA) was 8 ng/ml (normal range 0–5 ng/ml) and non-small cell lung cancer associated antigenCYF21–1 was 13.31 ng/ml (normal range 0.1–3.3 ng/ml). Other biochemical indicators were within the normal range.
The patient underwent a series of imaging examinations (Fig. ). Chest radiography on March 11, 2020 showed several nodules in the upper and lower segments of the left lung (Fig. a). Chest computed tomography (CT) on March 12, 2020 showed multiple solid nodules in the upper and lower left lung (Fig. b). The nodules had irregular outlines, with a maximum diameter of 65 mm, and some had a central cavity. A diagnosis of lymphoma was considered. Enhanced chest CT on March 16, 2020 (Fig. c–e) showed multiple “cauliflower like”, soft tissue masses in the left lung, partially fused, with a maximum diameter of 71.3 mm and a CT value of ~ 36 HU. Enhanced CT showed enhancement with a maximum value of 60 Hu. The boundary between the mass and pleura was not clear, and the mass could not be separated from the pleura. There was irregular thickening of the pleura and no enlargement of lymph nodes. A malignant tumor could not be excluded.
To clarify the pathological diagnosis, the patient underwent ultrasound-guided percutaneous needle biopsy of the left lung under local anesthesia on March 16, 2020. After consultation with our own and other hospitals(diagnostics were performed by Tianjin Fifth Central Hospital, Tianjin Cancer Hospital and Peking Union Medical College Hospital), the biopsy specimen was finally diagnosed as BA according to histomorphology and immunophenotype.
Wedge resection with safe margins may be the best treatment option for BA patients. However, if the lung is full of diffuse nodules, the whole lung may need to be removed, which seriously affects quality of life. Our patient was treated conservatively and followed up regularly. She was discharged on March 28, 2020.Her symptoms were managed through regular normal activities of daily living, strengthening respiratory protection, avoiding respiratory infection, and drug treatment to relieve dyspnea and cough.
To clarify the diagnosis, a double needle lung biopsy specimen was removed, 15 mm long, 1 mm in diameter. It was solid and gray white. Microscopically, there were irregular adenoid structures in a background of fibrosis and inflammation (Fig. a). The lesion had a two-layer cellular structure consisting of a basal and luminal layer, and had a lack of papillary structures. The micropapillae occasionally formed by non-ciliated cells germinated and burrowed into the alveolar cavity(Fig. b). The luminal layer was composed of type II alveolar cells and club cells. However, ciliated columnar cells and mucous cells in some flat areas could still be identified (Fig. c).The appearance was similar to adenocarcinoma in some areas, with alveolar destruction and stromal widening. Through careful observation, we found that the main reason for the stromal widening was edema and inflammatory infiltration. Unlike adenocarcinoma, there was a lack of thick collagen fibers (Fig. d). Tumor cells lacked atypia, mitosis and necrosis. A layer of material resembling the basement membrane surrounded the basal layer. The most important feature was a continuous layer of basal cells around the luminal layer.
Immunohistochemical staining for p63, p40 and cytokeratin (CK)5/6 clearly showed the continuity of the basal cells (Fig. a, b). The luminal cells and some basal cells stained positive for thyroid transcription factor (TTF)-1. The luminal cells expressed immunological markers of the terminal bronchioles (CKpan, CK7, Napsin A and CEA). A small number of mucous cells stained positive for periodic acid Schiff. The tumor showed a < 10% Ki-67 proliferation index (Fig. ). Finally, the case was pathologically diagnosed as BA of distal type.


A 62-year-old male with a medical history of hypertension, poorly controlled diabetes, and stroke with residual mild cognitive impairment and expressive aphasia presented to the hospital complaining of abdominal pain, vomiting, and ambulatory dysfunction for the last two days. He had a preexisting mid-metatarsal amputation of the left foot and was on aspirin 81 mg daily. He stated that he felt generally weaker than normal and was unable to ambulate in the ED. A noncontrast CT of the head was negative on presentation, and he was subsequently admitted for the management of dehydration secondary to suspected viral gastroenteritis. His nausea and vomiting improved shortly after admission. However, on the first day of hospitalization, the patient was being assessed by the medicine team as well as physical therapy and was found to be leaning backward and to the right when standing or attempting to ambulate. His family confirmed at this time that he had been doing this at home for a few days and had experienced several falls recently.
Given these findings, the neurology service was consulted and he was assessed on his second day of hospitalization. He was noted to have left-sided dysmetria. A CT angiogram of the head and neck showed a congenitally hypoplastic left vertebral artery and otherwise patent vertebrobasilar system with multifocal intracranial stenosis in the anterior circulation bilaterally. MRI of the brain was performed and confirmed a large area of acute/subacute infarct in the right cerebellar hemisphere without mass effect (Figure -). MRI at that time also showed restricted diffusion in a miniscule region of the AP on the right (Figure ). Echocardiogram performed showed an LVEF (left ventricular ejection fraction) of 60%, no regional wall motion abnormalities, normal wall thickness, and grade 1 diastolic dysfunction with trace aortic regurgitation. On day 5 of hospitalization, the patient became acutely more nauseous again and was noted to have projectile bilious vomiting. The nausea and vomiting lasted from minutes to hours and occurred with or without movement, typically following a meal. Notably, his neurologic examination was unchanged from the previous one, and the abdominal examination was unremarkable. The patient was sent for an abdominal X-ray obstruction series, which was negative. Subsequently, he was sent by the primary team for a repeat MRI of the brain to assess for worsening or a new infarct. The MRI was read as “stable” by the radiology service (Figure -). He was initially treated with ondansetron 8 mg every six hours as needed, which was ineffective. The neurology service was reconsulted for input regarding the intractable nausea and vomiting. He also had concomitant hiccups. The MRI was reviewed by the neurology service, and it was apparent that the stroke in the AP had extended (Figure ) and explained his APS. The stroke etiology was felt to be likely secondary to vessel-to-vessel embolization due to chronic atherosclerotic disease and less likely. The patient was monitored on telemetry for several days without any events or abnormalities noted.
He was started on a scheduled antiemetic regimen of metoclopramide 10 mg four times daily and ondansetron 8 mg every eight hours. Within one day, the nausea and vomiting was under control, and the patient was able to eat again without difficulty and was successfully discharged to rehabilitation.


A 66-year-old female patient suffered from cough, sore throat, and fever after contact with a confirmed case of COVID-19. On February 3 (illness day 10), oropharyngeal swab obtained from the patient tested positive for SARS-CoV-2 on quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays at the centers for disease control (CDC). She was admitted to the isolation ward for standard isolation treatment. On admission, the physical examination revealed a body temperature of 37.4 °C, 33 breaths per minute, blood pressure of 126/78 mmHg, and an oxygen saturation of 90% (indoor air). The patient’s oxygenation index was 243 mmHg (< 300 mmHg), the finger pulse oxygen saturation is less than 93%, and the respiratory rate was greater than 30 breaths per minute. According to the COVID-19 diagnosis and treatment guidelines, the patient is severe [].


The second patient is a 53 years old female with close fracture dislocation of left elbow after fall on an outstretched hand in a volleyball game (A and B). Her left elbow was operated in December 2018 (C). From the second patient, active ROM of elbow flexion was 140° (D), extension was 5° (E), supination was 80°, pronation was 70°, while passive ROM of elbow flexion was 140°, extension was 0°, supination was 85° pronation was 75°.


The third patient is a 38 years old female with neglected close fracture dislocation of the left elbow (terrible triad injury) (A). Patient had her elbow massaged, before operated in January 2019 (B).
From the third patient, active ROM of elbow flexion was 80° (C), extension was 10° (D), supination was 80° (E), pronation was 20° (F), while passive ROM of elbow flexion was 90°, extension was 5°, supination was 85°, pronation was 45°.


Our patient is a 38-year-old man with no significant medical history who initially presented to the outpatient clinic with a 1-month history of axial neck pain and right lateral thoracic pain. The pain was localized to the right 11th intercostal space and was exacerbated by inspiration. He reported no trauma or prior inciting event. On physical examination, he had tenderness to palpation about his posterior neck. Motor and sensory exams were within normal limits with no obvious neurologic deficit. Initial plain AP and lateral radiographs of the cervical spine were normal (Figure ). The patient was initially treated conservatively with NSAIDs and physical therapy. However, 6 weeks later, the patient returned without symptomatic improvement and new onset right upper extremity radiculopathy.
MRI of the cervical spine was obtained and demonstrated a nongeographic, destructive lesion in the posterior elements of the cervical spine arising from the spinous process of C7 and evidence of spinal cord compression (Figure ). CT scan of the cervical spine demonstrated erosive changes to the C7 spinous process (Figure ). A malignancy workup was performed, and an oncology consult was obtained. Chest/abdomen/pelvis CT scan revealed metastatic disease of the right 11th rib; however, no primary mass was identified. Bone scan showed increased uptake in the right 11th rib, but no other evidence of metastatic bone disease. No primary malignancy was identified on the initial screening. Given the nature of the patient's symptoms and MRI findings, the patient was indicated for surgical intervention for primary resection of the tumor.
A C6–T1 laminectomy was performed to gain access to the mass. The tumor was identified and wide en bloc resection of the mass was performed. The specimen consisted of the lesion surrounded by healthy appearing tissue (Figure ). Frozen section of excised tissue was positive for numerous malignant cells with negative margins. Posterior spinal instrumentation from C5 to T2 was then performed (Figure ). Histology slides demonstrated bony trabeculae with both, tumor cells and lymphocytes, on low power field (Figure , A). Dark small lymphocytes and large square seminoma cells were present on high power field (Figure , B). Placental alkaline phosphatase stain (Figure , A) and proto-oncogene c-Kit (CD117) stain (Figure , B) were positive for seminoma cells. Final pathology was positive for seminoma, confirming this diagnosis. A testicular ultrasonography was performed to investigate for the presence of a primary testicular tumor, but was negative for malignancy. The patient was discharged from the hospital on postoperative day 5 with orthopaedic and oncologic follow-up. He has since recovered well and has undergone three cycles of chemotherapy with cisplatin, vinblastine and bleomycin. Postoperative radiographs show hardware in excellent position. At 24-month follow-up, he was asymptomatic with no evidence of recurrence of the spinal mass or progression of the rib lesion. He continues to be monitored with periodic spine and testes MRIs and chest CT scans.


The patient was an otherwise healthy 17-year-old male who presented with left eyelid swelling, retrobulbar pressure sensation, and occasional diplopia worsening over the preceding few weeks. MRI revealed an infiltrative, enhancing, multi-compartmental lesion in the left inferolateral extraconal orbit associated with left-sided proptosis, optic nerve displacement, suspected osseous erosion of the orbital floor, and nodular lesions along the left frontal scalp and buccal region. Initial transconjunctival orbital biopsy was suggestive of a non-specific, benign, fibro-inflammatory lesion, but oral prednisone therapy resulted only in minimal symptom improvement without significant radiographic changes. An additional minimally invasive periorbital biopsy was more consistent with an atypical lymphoid infiltrate with prominent B cell and polytypic plasma cell populations—considered potentially concerning for marginal zone lymphoma. Of note, PET-CT imaging was negative for evidence of lymphoma elsewhere. During the next several months, the patient’s ophthalmic symptoms progressed, and he developed new neurological symptoms (facial numbness and tingling). Interval enlargement of the orbital lesion was noted on repeat MRI (Fig. a-e).
Initial surgical debulking of the left intraorbital retrobulbar mass was performed by a multidisciplinary surgical team including skull base and pediatric neurosurgeons and plastic surgery faculty; via a left orbitozygomatic craniotomy, the bulk of the lesion bordering the extraocular muscles and the portion extending into the infratemporal fossa was resected and sent for histopathological analysis. A fibroinflammatory process characterized by a dense lymphohistiocytic infiltrate (Fig. a) containing abundant plasma cells (Fig. c) was observed. Immunohistochemical staining for IgG and IgG4 highlighted a large subpopulation of IgG4-positive plasma cells (greater than 50 per high-power field) (Fig. f), and the overall IgG4/IgG expression ratio was greater than 0.4 (Fig. e-f). Vague areas of storiform fibrosis (Fig. b) and focal obliterative phlebitis (not shown) were also identified. Immunostaining for ALK-1, which is useful when trying to establish a diagnosis of inflammatory myofibroblastic tumor, was negative (Fig. d). Taken together, these features favored the diagnosis of IgG4-RD.
Postoperative imaging revealed radical resection at the level of the optic nerve with residual enhancing mass in the infraorbital region, the left cheek, and the maxillary sinus (Fig. a). The patient continued to experience left eyelid swelling, diplopia, and cheek numbness. He received two doses of second-line rituximab (since he previously failed first-line corticosteroids), but despite this, an MRI obtained approximately 2 months after initial surgical debulking revealed extracranial disease progression in the maxillary sinus and fat planes of the left cheek (Fig. b).
Therefore, nearly three months after the initial debulking, a second debulking surgery of the progressive extracranial disease was attempted by plastic surgery; dissection and en bloc resection of the mass from the caudal margin of the tarsal plate down into the cheek, around the deep muscles of the face, and through to the deep extension to the infraorbital fissure was performed, and specimens were again sent to pathology. Surprisingly, histopathological findings of this second surgical specimen revealed new, informative diagnostic features. While a diffuse inflammatory infiltrate characterized by small lymphocytes, histiocytes, and IgG4-positive plasma cells (up to 50–60 per high-power field) was still present (Fig. g-i, l) and was associated with a somewhat elevated plasma cell IgG4/IgG expression ratio (0.3), there was a lack of apparent storiform architecture in the fibrous stroma, and obliterative phlebitis was absent (Fig. h-i). Furthermore, large S-100-positive histiocytes with foamy cytoplasm and hypochromatic nuclei with prominent nucleoli were newly observed, and there was evidence of emperipolesis (Fig. j-k). Although the inflammatory component seen here was reminiscent of IgG4-RD given its similarity to the previous specimen, new findings more strongly supported a different final diagnosis: RDD.
Following extracranial debulking, there was persistent multi-directional diplopia; however, MRIs obtained at approximately 1 month (Fig. c) and 4 month (Fig. ) follow-up showed interval decrease in lesion size consistent with surgical resection, and stabilization of disease thereafter, including resolution of proptosis. Post-surgical cicatricial ectropion of the left lower eyelid along with myogenic ptosis of the left upper eyelid were subsequently repaired by oculoplastic surgery. No further treatment was required.


A 43 years old Chinese woman presented to our emergency department with progressively general weakness for 1 day. She had experienced 1 episode of sudden onset of flaccid paralysis of lower extremities for a couple of minutes, but it spontaneously resolved by itself 5 days before admission. Neither she nor her family members had previously experienced any such attack. She denied any history of vomiting, diarrhea, and abdominal pain. Moreover, there was no history of recent strenuous exercise or the use of diuretics.
On physical examination, her blood pressure was normal (122/71 mm Hg), body temperature was 37°C, respiration rate was 18 breaths per minute and heart rate was 78 beats per minute. She looked very thin with 54 kg body weight and 170 cm body height, indicating low body mass index (18.6 kg/m2) (normal range: 18.5–22.9). No flaccid paralysis of the limbs or areflexia of the joints at the time of admission was observed. Other physical examination findings were unremarkable.
The results of biochemical studies on admission were shown in Table . The predominant findings were marked hypokalemia (2.2 mmol/L) with metabolic alkalosis (HCO3–: 36.8 mmol/L) and renal potassium wasting (transtubular potassium excretion gradient: 9). Moreover, the relatively low urine sodium and chloride levels were also noted. Serum magnesium level, thyroid function test, and cortisol level were within normal limit. Treatment for hypokalemia was initiated by oral and intravenous supplementation of potassium (2.2 mmol/L). Serum potassium level remained low (3.1 mmol/L) after oral potassium supplementation and intravenous infusion of potassium chloride (total potassium supplement, 160 mEq/L within 18 hours).
Initially, AN with remote vomiting was highly suspected as the etiology of hypokalemia because laboratory data were compatible with remote vomiting or diarrhea and in accordance with the hypokalemia differential diagnosis flow chart (Fig. ). She strongly denied the habits of self-induced vomiting or having diarrhea, but she admitted to drinking a lot of water recently to prevent a urinary tract infection.
Thus, the other etiologies apart from AN were investigated. High aldosterone level (290.3 pg/mL) and low renin level (2.74 pg/mL) with extremely high aldosterone-to-renin ratio (105.8) biochemically indicated the diagnosis of PA. Contrast enhanced computed tomography scan of abdomen revealed a well-circumscribed homogenous mass, 2.2 cm in diameter, in the inner arm of the right adrenal gland, confirming the diagnosis of PA (Fig. ). Laparoscopic right partial adrenalectomy of right adrenal mass was performed owing to persistent hypokalemia. Macroscopic examination of the extracted adrenal mass found an encapsulated 2.4 × 1.3 cm golden yellow nodule. Microscopic examination concluded to the adenomatous nature of this adrenocortical nodule without malignancy signs. After surgical treatment, biological abnormalities (hypokalemia and metabolic alkalosis) and hormonal status (plasma aldosterone and renin activity) returned to normal level. After discharge, no further hypokalemia was found during a regular one and half year follow-up at the outpatient department without any treatment.


A 55-year-old Chinese male patient with intermittent fatigue was examined in this study. The patient's symptoms started 17 years ago with fatigue without an obvious cause, followed by occasional limb weakness and stiffness; this was accompanied with palpitations. Hypokalemia was diagnosed by testing blood electrolyte levels. The patient took potassium supplements (potassium citrate) irregularly; however, this did not normalize the patient's potassium levels. Two weeks before the patient was admitted to the hospital, the above-mentioned symptoms were aggravated after drinking juice. Blood pressure and body mass index (BMI) of the patient were 104/76 mm Hg and 20.76 kg/m2, respectively. Cardiopulmonary, abdominal, and neurological examinations showed no abnormalities. The patient's mother had been previously diagnosed with hypokalemia and died 10 years ago. His parents were nonconsanguineous, and none of his siblings had hypokalemia.
The results of the main laboratory tests of the patient have been summarized in Table . The laboratory tests showed hypokalemia, hypomagnesemia, and mild hypochloremia. Urine analysis revealed inappropriate kaliuresis, abundant natriuresis, abundant chlorosis, and hypocalciuria. The supine-upright test showed hyperreninemia and hyperaldosteronism. Electrocardiogram, abdominal ultrasound, and adrenal computed tomography revealed no abnormalities.
In the current study, according to OGTT, islet function test, and diabetes antibody test results, the patient was diagnosed with T2DM. The criteria for T2DM diagnosis are high blood glucose (fasting plasma glucose ≥7.0 mmol/L, or 2 h-postprandial plasma glucose ≥11.1 mmol/L during OGTT, or glycosylated hemoglobin ≥6.5%, or random plasma glucose ≥11.1 mmol/L) with normal or elevated insulin levels; the diabetes-related antibodies are usually negative.[
After obtaining written informed consent from the patient and his family, and the approval of the ethical review committee of The First Hospital of Jilin University (2016–397), the SLC12A3 gene of the patient (Fig. , II4) was analyzed. The results showed 2 heterozygous mutations in the exon area of SLC12A3 (Fig. ): a missense mutation c.1077C>G in exon 8; the variant possessed lysine instead of asparagine at position 359 (p.N359K, NM_000339); this mutation has been reported as a pathogenic mutation for GS and a novel insert mutation c.784_785insTCATTGGCGTGGTCTCGG in exon 6, leading to p.I262delinsIIGVVSV. In addition, the SLC12A3 genes of 9 other family members of the patient were analyzed, the missense mutation p.N359K was found in the older brother (Fig. , II1), youngest sister (Fig. , II8), and son of the patient (Fig. , III2).
The OGTT results and blood potassium levels of the pedigree (Fig. ) are summarized in Table . The patient's older brother (Fig. , II1) and youngest sister (Fig. , III8), who carried the pathogenic mutation, were diagnosed with T2DM and impaired glucose tolerance, respectively.
Based on the typical symptoms, laboratory test results, and gene analysis, the patient was diagnosed with GS. The patient was prescribed oral supplements of potassium magnesium aspartate (316 mg/280 mg, 3 times per day), potassium chloride (500 mg, 3 times per day), and spironolactone (20 mg, 3 times per day). He was recommended to maintain a high potassium diet. The blood glucose levels were maintained using the drug acarbose (50 mg, 3 times per day). Blood potassium and blood magnesium levels fluctuated between 3.02 and 3.54 mmol/L, and 0.63 to 0.71 mmol/L, respectively. There were no adverse effects due to the drugs. Although acarbose was stopped after half year of the treatment, fasting plasma glucose levels and postprandial plasma glucose levels were still maintained at 5 to 6 mmol/L and 6 to 9 mmol/L, respectively. The patient was followed up for 2 years.


We report an 83-year-old Caucasian male with OI type IV. The patient fell into a track bed with his electronic wheelchair. After recovery and transportation to the emergency department, a femoral shaft fracture was diagnosed. Although the hospital was a level-1 trauma center, they contacted our university medical center due to the rareness of the case.
The patient was transferred to us via helicopter. After arrival at our emergency department, we performed 3D computed tomography to better understand the morphology of the fracture (). Due to the underlying disease and the bone structure in the 3D CT, we decided that a sufficient elastic osteosynthesis would be necessary to prevent further fractures or implant failure.
Matters were made worse by the patient's obesity (BMI: 74.4). Besides OI, he also suffered from the following comorbidities: constructive pulmonary disease (COPD), obstructive sleep apnea syndrome (OSAS), and arterial hypertonia. Surgery was performed 5 days after the accident and 2 days after the interhospital transfer of the patient. The patient was placed in a supine position, and the fracture site was prepared using a lateral approach.
The alignment of the femur was reconstructed by careful manual extension on the leg (). Then, the three parts of the fracture were reduced with sharp reduction forceps (). When sufficient reduction was achieved, a 3.5 mm elastic stable intramedullary nail (ESIN) was carefully inserted from a retrograde position (). As the ESIN was placed, the reduction forceps were removed, and the osteosynthesis proved to be stable. The wound was closed, and the leg was elastically wrapped. Additionally, the thigh was immobilized with a cast for one week.
A postoperative weight-bearing restriction was imposed for six weeks. The patient received physiotherapeutic training after the cast was removed. Moreover, pain medication and thrombosis prophylaxis were prescribed. Eight days after surgery, the patient was released from hospital. The radiograph showed sufficient bony healing six weeks after the osteosynthesis (). Three months after the accident, the patient was able to walk without further support aside from his gait orthoses.
One month later, the patient fell again when he tried to mobilize himself. He came to our emergency department with the help of his wife, and a peri-implant fracture was diagnosed without failure of the ESIN (). Closer analysis of the fracture showed almost no dislocation, and the elastic nail was stable. Thus, we recommended a conservative treatment with weight-bearing limitation for 6 weeks and immobilization with a stiff orthosis.
The patient was treated in our outpatient clinic, and the radiograph showed sufficient bony healing six weeks after the refracture (). A weight-bearing restriction of 15 kg for one more week was imposed. Gradually, the weight bearing was increased 15 kg each week. After 6 weeks, the patient reached full weight bearing. Thus, 12 weeks after the second accident, he was able to walk again with his gait orthosis, but without crutches. Seven months after the second accident, the patient died due to pneumonia. By that time, he was 84 years old.


A 44-year-old man felt generalized fatigue and took the day off from work. His son called him on the same day, but he did not respond. When the son visited his house, he found the patient unconscious and called an ambulance. He had no remarkable medical history. He was a never-smoker and drank 20 g of ethanol per day. He worked as a truck driver and lived with his only son after his divorce. His work zone was not located in any of the districts that were reported to have COVID-19 infections.
When the emergency medical technicians checked him, he had a tonic convulsive posture with severe hypoxia, and he was transported to our hospital under bag-valve-mask ventilation with high-concentration oxygen. On arrival, his Glasgow Coma Scale was E1V2M3. A physical examination revealed the following findings: blood pressure of 174/130 mmHg; heart rate of 140 beats per minute; a respiratory rate of 30 breaths per minute; SpO2 of 75% under room 15 L per minute of oxygen; and body temperature of 36.9 °C. A venous route was immediately secured, followed by endotracheal intubation.
An arterial gas analysis revealed the following findings: pH: 7.092; PCO2: 54.2 mmHg; PO2: 54.5 mmHg; base excess -15.0 mmol/L; and lactate: 6 mmol/L. Electrocardiography revealed sinus tachycardia. A chest X-ray revealed a bilateral ground-glass appearance (Figure ).
Cardiac echo showed hyper-dynamic left-ventricular wall motion. Whole-body CT revealed a bilateral ground-glass appearance in the ventral lung fields and bilateral consolidation in the dorsal lung fields (Figure ).
The pancreas was normal. The main results of a blood analysis were as follows: WBC count: 23,400/μL (neutrophil 87%, lymphocyte 6%, monocyte 6%); hemoglobin: 16.5 g/dL; platelet count: 22.0×104/μL; total protein: 7.0 g/dL; albumin: 4.3 g/dL; glucose: 177 mg/dL; HbA1C: 5.5%; total bilirubin: 1.5 mg/dL; aspartate aminotransferase: 322 IU/L; alanine aminotransferase: 79 IU/L; lactate dehydrogenase: 1,108 IU/L; blood urea nitrogen: 7.4 mg/dL; creatinine: 0.51 mg/dL; amylase: 413 (pancreas 76%) IU/L; creatine phosphokinase (CK): 44,139 IU/L; sodium: 110 mEq/L; potassium: 4.2 mEq/L; chloride: 79 mEq/L; brain natriuretic peptide: 760.1 pg/mL; C-reactive protein: 22.2 mg/dL: prothrombin time international normalized ratio: 1.02; activated partial thromboplastin time: 34.6 (26.6) seconds; fibrinogen: 242 mg/dL; D-dimer: 1.5 μg/mL; human immunodeficiency virus (HIV) antibody: negative; pneumococcal urinary antigen test: negative; legionella urinary antigen test: negative; rapid influenza diagnostic test: negative; microscopic finding of sputum: negative: and urine drug screening test: negative. Later, β-d glucan, rheumatoid factor, and anti-neutrophil cytoplasmic antibody were all found to be negative. He received a tentative diagnosis of pneumonia of unknown causes accompanying severe ARDS, rhabdomyolysis, and pancreatitis.
As he showed deterioration of PaO2 [PaO2/FiO2 (P/F) = 50] and a Murray score of 3.2, he underwent mechanical ventilation under 1.0 FiO2 and 10 cmH2O with positive end-expiratory pressure (PEEP) and received indwelling venovenous ECMO (MERA centrifugal blood pump system HAS-CFP; MERA NHP exelung NSH-R HPO-23WH-C; Senko Medical Instruments, Tokyo, Japan) with the right jugular vein (return side, 14 Fr) and right femoral vein (drainage side, 20 Fr) as the exit. As this event occurred during the night shift, we did not attempt supine therapy before introducing venovenous ECMO. He also showed hypotension and therefore underwent infusion of noradrenalin followed by vasopressin and 200 mg of hydrocortisone. Due to concerns of pneumonia, he received 1.5 g of meropenem and 500 mg of azithromycin in addition to an infusion of 5 g of γ-globulin and 40 ml of glycyrrhizin as antibacterial and antivirus treatments respectively.
After the induction of ECMO, the mode of mechanical ventilation was changed to a lung rest setting (0.25 FiO2 and 5 cmH2O with PEEP). Additional cardiac echo showed diffuse hypokinesis with a 30% ejection fraction, and troponin T became positive [207 pg/mL (normal range: <14 pg/mL)] on the first hospital day, and so he was diagnosed with myocarditis as a complication. On the second day, his blood pressure increased, resulting in a reduction in the vasopressor administration. His P/F remained under 100. On the third day, inflammatory data remained high, and hence azithromycin was replaced with levofloxacin. However, this led to skin reddening and he was switched back to azithromycin. A complication of anemia, thrombocytopenia, and coagulopathy required blood transfusion. A polymerase chain reaction (PCR) test for COVID-19 using sputum through the endotracheal tube without bronchoalveolar lavage (performed twice) and initial cultures of sputum, urine, and blood were all negative.
On the fifth day, the inflammatory data remained moderate, and hence meropenem was replaced with linezolid and piperacillin/tazobactam. On the same day, in an attempt to withdraw ECMO, the mechanical ventilation setting was changed from 5 to 10 cmH2O for PEEP and from 0.25 to 0.4 for FiO2. This resulted in the P/F increasing to over 100. After the circulation flow of ECMO was reduced from 3 to 1 L/minute, the P/F remained over 100; hence ECMO was ceased, and the cannulations were removed (Figure ).
As the patient was thought to require long-term mechanical ventilation, he underwent tracheostomy on the eighth hospital day. Sedative administration was ceased, and a negative water balance was targeted by limiting the infusion volume and the use of diuretics. He showed a transient decrease in his P/F by the formation of atelectasis due to bloody sputum; however, the average P/F improved day by day. On the 12th hospital day, his P/F exceeded 300 under 5 cmH2O for PEEP and 0.25 FiO2; hence mechanical ventilation was ceased (Figure ).
He recovered his ability to excrete sputum by himself, and tracheal cannulation was removed on the 13th hospital day. Even after ceasing all drugs for lung and inflammation, his pneumonia, rhabdomyolysis, and pancreatitis did not recur. He was discharged on the 22nd day on foot. The troponin T level remained high (334 pg/mL) even after the CK level normalized, so he was followed up as an outpatient. The serum virus neutralization assay performed as a serological test using pair serum samples with a more than two-week interval for Coxsackievirus B4 showed a four-fold increase in titer (from x64 to x256). Finally, the troponin T level returned to the normal range and showed no subsequent complications.


A 58-year-old woman with a medical history of hypothyroidism and essential hypertension presented with severe dry cough and nasal congestion for 2 weeks. Three days before presentation, she had noticed a bruise on her right lateral chest wall which gradually increased in size and became painful with radiation to her back. The patient denied any recent history of trauma to the area. Her review of systems was positive for the presence of dry cough. Physical examination revealed a bulging, palpable, and tender ecchymotic lesion over the right ninth and 10th ribs in addition to clear lungs (Figure ). Vitals were unremarkable. Laboratory test results were significant for alanine aminotransferase level of 41 U/L, aspartate aminotransferase level of 62 U/L, creatinine kinase level of 493 U/L, white blood cell count of 17,800 cells/uL, platelet count of 567,000 cells/uL, international normalized ratio 0.9, and a positive nasal swab for influenza A.
Abdominal computed tomography showed herniation of the uninjured liver through a diaphragmatic defect into the thoracic cavity (“hump sign”) with a concomitant intercostal herniation between ninth and 10th ribs (Figure ). Also reported was the presence of abdominal wall soft tissue stranding (or edema). Surgical services were consulted, and the patient was managed conservatively with opiate analgesia, intravenous hydration with normal saline, cough suppression, and Oseltamivir. She was then discharged with a close medical and surgical follow-up. In the 1- and 6-month follow-ups, the patient had minimal symptoms in the form of abdominal contour change, with the resolution of ecchymosis and tenderness to palpation, which was previously present. Laboratory test results had returned to reference range on the follow-up visit.


A client-owned 6-year-old, 13-kg, female neutered Beagle was presented to the neurology service in the small animal clinic of the University of Zurich. The dog had a history of 1 generalized tonic-clonic seizure and multiple episodes of myoclonus seizures, which usually were precipitated by auditory or visual triggers. Blood biochemistry and hematology were performed by the referring veterinarian, including fasted and postprandial bile acid concentrations, and results were within the reference range. The dog was treated with 2 mg/kg phenobarbital PO q12h for 1 month before presentation at the University of Zurich and the blood phenobarbital concentration was 14.9 mg/L. Clinical and neurological examinations did not identify any abnormalities. The neuroanatomical localization was the forebrain. Based on the signalment and seizure semiology, LD was strongly suspected. Blood samples were obtained and genetic testing for the NHLRC1 gene mutation was performed in a commercial laboratory using PCR as described previously. The dog was sedated with IV midazolam (0.2 mg/kg) and butorphanol (0.2 mg/kg), and anesthesia was induced with IV propofol (2.5 mg/kg) and maintained with sevoflurane gas. During anesthesia the dog received Ringer's actetate (3 mL/kg/h).
Magnetic resonance imaging of the brain was performed with a high-field 3-Tesla MRI scanner (Philips Ingenia, Philips AG, Switzerland) equipped with a head/neck/spine coil. The dog was positioned in dorsal recumbency. Studies included gradient echo pre- and postcontrast 3D T1-weighted (T1W) images (echo time [TE] = 4.1 ms, repetition time [TR] = 8.9 ms; slice thickness = 0.6 mm), spin echo 3D T2-weighted (T2W) images (TE = 180.9 ms, TR = 2300 ms, slice thickness = 0.7 mm) and transverse fluid attenuation inversion recovery (TE = 125 ms, TR = 11 000 ms, slice thickness = 2.5 mm) images. Gadopentetate dimeglumine (0.1 mmol/kg) was administered IV for postcontrast image acquisitions.
Proton magnetic resonance spectroscopy was performed before contrast media administration. The 1HMRS protocol used was the same as previously described with voxel positioning in the left thalamic area (TE = 32 ms, TR = 2000 ms, 240 signal averages). Proton magnetic resonance spectroscopy data were analyzed using the LCModel software, which fits the spectra as a linear combination of model spectra of metabolites presumably present in the tissue. Simulated spectra of 20 metabolites (alanine, aspartate, glucose, creatine, phosphocreatine, glutamine, glutamate, glycerophosphocholine [GPC], phosphocholine, lactate, mI, NAA, N-acetyl-aspartyl-glutamate, scyllo-inositol, glutathione, taurine, glycine [Gly], phosphoethanolamine [PE], ascorbate, and γ-aminobutyric acid) were used. Contributions from lipids and macromolecules were simulated in the LCModel. Estimates of the mmol/L concentrations of the metabolites were calculated with the unsuppressed water signal as reference (TE = 32 ms, TR = 2 seconds), estimating a pure gray mater water concentration of 43 300 mmol/L (LCModel setting: WCONC = 43 300) and correcting for relaxation attenuation by an factor of 0.7 (ATTH2O = 0.7). In addition, the metabolite ratios to total creatine (tCr, the sum of creatine and phosphocreatine) were calculated.
A cisternal cerebrospinal fluid collection was performed under aseptic conditions at the end of the MRI investigation.
In addition, MRI and 1HMRS with voxel positioning in the thalamic area of 12 healthy 3- to 6-year-old Beagles (with the same acquisition and anesthesia protocol with butorphanol, propofol, and sevoflurane) and archived from an independent research study was used for comparison (animal permission number: ZH272/16). Signal-to-noise ratio (SNR) and full width at half maximum (FWHM) were comparable between the investigated dog (SNR, 10; FWHM, 4) and healthy controls (SNR range, 9-18; median, 14.5; FWHM range, 2.9-5.9 Hz; median, 4.4 Hz) (Figure ). Metabolites and their ratios to tCr of the Beagle with LD were considered increased or decreased if they were outside of the range of the healthy Beagle dogs' metabolite concentrations and their ratios to tCr.
Magnetic resonance imaging examination of the investigated dog brain did not identify any abnormalities.
The results of 1HMRS are presented in the Table and Figure . Compared to metabolite concentrations found in the healthy controls, the molar concentrations of the sum of glutamate and glutamine [Glx], NAA, and the sum of mI and Gly [mI + Gly] were decreased in the LD dog whereas increased concentrations of tCho and PE were found. Abnormal ratios to tCr were observed for Glx (decreased), tCho (increased), and PE (increased).
In the cerebrospinal fluid, cell count, cell types, and protein concentration were within normal limits. The genetic test confirmed LD.
The phenobarbital dosage was adjusted appropriately, but the Beagle still continued to have myoclonus seizures with increased frequency. Therefore, treatment with phenobarbital was continued for generalized tonic-clonic seizures, and levetiracetam (20 mg/kg PO q8h) was added in an attempt to better control the myoclonus seizures., Additionally, the dog was fed a commercial food to support the nervous system. The owner reported improvement with no additional tonic-clonic seizures and decreased frequency (approximately 50% according to the owner's observations) of myoclonus seizures.


A 60-year-old man was scheduled to undergo his third aortic root replacement using a homograft because of infectious endocarditis in the aortic valve. At the age of 58, he underwent Bentall operation, mitral valve replacement, and Maze operation because of aortic regurgitation, mitral regurgitation, and atrial fibrillation. Two months later, because infection with methicillin-resistant coagulase-negative staphylococci in the artificial vessel was indicated, a second aortic root replacement surgery with coronary artery bypass grafting surgery (CABG) were performed. This time, because he developed a slight fever that persisted for about 3 weeks, he visited our hospital. Infectious endocarditis (IE) in the aortic valve (Fig. a), a false aneurysm in the dorsum of the artificial vessel (Fig. b, c), and mediastinitis (Fig. c) were indicated by echocardiography and computed tomography. As the infection of the artificial vessel was repetitive, a third aortic root replacement using a homograft and CABG were scheduled.
During the hospitalization before the surgery, administration of dopamine, dobutamine, and isoproterenol was started as his circulation dynamics became unstable because of complete atrioventricular block. The examination of blood data before the operation is shown in Supplementary Table . On the operation day, anesthesia was induced with a support of catecholamine, followed by the establishment of a cardiopulmonary bypass (CPB) from the femoral artery and vein before starting the operation. Although the operation was difficult and accompanied with bleeding because of severe adhesion attributed to the two previous operations, aortic root replacement using a homograft and CABG were performed as planned; two saphenous vein grafts were connected from the aorta to the left anterior descending artery and right coronary artery. At the time of withdrawal from CPB, we had difficulty in maintaining hemodynamics because of bleeding from the surgical site, which led to hypovolemic shock. Subsequently, his cardiac function deteriorated. Therefore, VA-ECMO was established and the operation was finished.
After the operation, mechanical ventilation and VA-ECMO support were continued in the intensive-care unit. The bleeding from the drains continued. His activated clotting time was in the range of 160 to 180 s without the use of heparin. At postoperation day 1 (POD1), echocardiogram demonstrated cardiac hypofunction, but thrombi were not detected in the right and left atria and ventricles. Improvement of cardiac function was not obtained, pulse pressure decreased gradually, and central venous pressure increased gradually. At POD3, an intrathoracic and pericardial hematoma was suspected and evacuation of hematoma was performed for cardiac tamponade.
The hematoma in the thoracic cavity and pericardium was removed by operation. However, cardiac function was not ameliorated. As the visualization of the ascending aorta by transesophageal echocardiography was unclear (Fig. a), direct echography in the ascending aorta was performed by the operator to observe the inside of the homograft. The homograft was completely occluded by a thrombus (Fig. b, c, d), which was about 4 cm long and was located at the origin of the ascending aorta; however, as the surgeon confirmed the bypass graft patent, the entries of the coronary arteries were intact because entries of the coronary arteries were moved to peripheral side by CABG operation. The thrombus inside the homograft was removed (Fig. e, f) and the operation was finished.
After the operation, the pulse pressure was slightly improved but cardiac function was not ameliorated. The patient had brain infarction at POD3 and died at POD5.


A 23-year-old gentleman, with known case of hepatitis B and PNH, presented to the emergency department with abdominal pain and vomiting. He was previously diagnosed with a loss of fluorescein-labeled proaerolysin variant (FLAER), CD157 on granulocytes and monocytes (80% loss), and CD59 on erythrocytes (45% loss) on flow cytometry after extensive workup for anemia following a road traffic accident.
Previous workup included a trephine bone marrow biopsy which showed megaloblastic changes in erythroid precursors, a normal red blood cell fragility test, a reticulocyte count of 31%, a lactate dehydrogenase level (LDH) of 3,764 U/L, and a few spherocytes and target cells on peripheral smear.
He had been advised bone marrow transplant, but was lost to follow-up.
Now, on this presentation, he had marked pallor, scleral icterus and a mildly tender abdomen. Workup showed a low hemoglobin and platelet count, AKI and hypokalemia. A CT scan of the abdomen and pelvis with contrast was done, which revealed splenic and bilateral renal vein thrombosis, hepatomegaly with thrombosis of right hepatic vein, middle hepatic vein and anterior division of right portal vein, mild abdominopelvic ascites, mild pericardial effusion and bilateral lobar nephronia. The bilateral renal vein thrombosis can be seen in Figures , .
Hospital course and management
The patient was admitted and managed on the lines of bicytopenia, AKI, extensive venous thrombosis, renal abscess and PNH. A multidisciplinary approach was adopted with hematology, nephrology, urology, interventional radiology and gastroenterology on board. He received both platelet and packed red blood cell transfusions, intravenous hydration and intravenous antibiotics. He underwent abscess drainage and bilateral double J (DJ) stenting. Anticoagulation was not offered initially due to a low platelet count, but heparin was started eventually. Additionally, eculizumab was unavailable.
His hospital stay lasted a total of seven days. Hematological and biochemical trends can be seen in Tables , . Clinically, he displayed a marked improvement following abscess drainage and bilateral DJ stent placement. Blood and body fluid cultures revealed Escherichia coli, for which he received intravenous meropenem and ertapenem. At the time of discharge, his creatinine had dropped from an initial value of 5.3 mg/dL to a static 2.7-2.8 mg/dL, hypokalemia had resolved, blood counts had improved and he was afebrile, tolerating orally and mobilized. He was advised to follow up as an outpatient to discuss further treatment options.


A 57-year-old male patient was admitted to our department for kidney transplantation. He was suspected to have diabetes when he was 50 years old, because of an elevated hemoglobin A1c (HbA1c) level at 8.7%. Four years later, when he was referred to our hospital for kidney transplantation, his serum creatinine level was elevated, while his HbA1c level had decreased to 4.8%. When his serum creatinine level was elevated to approximately 6 mg/dL, he consented to undergo preemptive kidney transplantation. The donor was his 57-year-old female dizygotic twin; however, non-donor-specific antibodies were detected. Immunosuppression was performed using rituximab (200 mg/body), tacrolimus (0.1 mg/kg/day; adjusted by trough levels of 6-8 ng/mL), mycophenolate mofetil (2,000 mg), and methylprednisolone (20 mg/day before transplantation; 500, 250, and 125 mg/day on the day of transplantation, day 1 after the operation, and day 2 after the operation, respectively). The transplant procedure was completed without any complications, with a cold ischemia time of 2 hours and 23 minutes. Diuresis began 5 minutes after declamping. The Lich-Gregoir method was adopted without the use of a ureteral stent [] ().
After the surgery, the urine output and serum creatinine levels improved until postoperative day 4 (POD 4). On POD 5, he complained of sudden abdominal pain with decreased urine output. Computed tomography (CT) revealed fluid collections in the right postperitoneal cavity (). In anticipation of a potential ureteral complication, retrograde stenting was attempted but was not accomplished owing to edema of the ureteral orifice. No leakage of contrast medium was seen on cystography, indicating a suspected ureteral rupture. On surgical examination performed on POD 8, we noted a small perforation in the middle portion of the right ureter (). Further, pyeloureteral neoanastomosis was performed using 3-0 vicryl with a ureteral stent and drainage tube ().
The pyeloureteral neoanastomosis showed persistent urine leakage along with a higher creatinine level than that in the serum for seven days after the repair; further, the coagulation FXIII level decreased to 48%. Based on the suspicion of a fistula, fibrogammin (240 IU/vial, 5 vials/day; CSL Behring, King of Prussia, PA) was administered for 5 days, which led to reduced drainage. Because there were no signs of leakage (), the ureteral catheter and drainage tube were removed. His creatinine levels were stable at approximately 1.6 mg/dL (nadir: 1.49 mg/dL); however, there were no side effects, such as viral infections. The patient showed no complications or immunosuppression on follow-up after 2 years.


A 32-year-old man presented with 2 weeks of painful and blurry vision in his right eye (OD) with watery discharge. His social history was notable for sex with men, with one sexual partner in the past year. He reported safe sexual practices. His urine tested positive for amphetamines. He denied use of illicit intravenous drugs. Vision was 20/400 OD and 20/70 in the left eye (OS), improving to 20/200 and 20/30 with pinhole. The intraocular pressure (IOP) was normal in both eyes (OU) and there were no relative afferent pupillary defects (RAPD) OU. He had new heterochromia, with a dark green iris OD and a light blue iris OS. No neovascularization of the iris was seen. Slit lamp exam OD revealed upper and lower eyelid edema, moderate injection of the conjunctiva, corneal edema with keratic precipitates and a disorganized hyphema attached to the peripheral iris. There was a significant degree of anterior chamber cell and flare, along with dense vitritis and optic nerve edema. The left eye showed signs of mild anterior uveitis only. The patient was diagnosed with panuveitis OD and anterior uveitis OS.
Blood tests revealed a positive RPR (1:256), positive Treponema pallidum antibody, HIV-1 antibody with CD4 count of 36, and CMV IgG. Blood tests were negative for CMV IgM, Tuberculosis interferon antigen, Toxoplasma gondii IgM and IgG, and lysozyme. Other abnormal findings were leukopenia, an elevated ESR (> 128 mm/hr), and elevated liver enzymes.
The patient was admitted and started on a darunavir, cobicistat, emtricitabine, tenofovir and alafenamide combination tablet based on his HIV resistance profile. Syphilis was treated with intravenous (IV) Benzylpenicillin 4 million units every 4 h for 14 days followed by three weekly benzathine penicillin 2.4 million units intramuscular (IM) injections, given his degree of immunosuppression.
Ten days later, his vision OD was 20/300 with pinhole improvement to 20/125. There was no RAPD and IOP was normal. The conjunctiva was clear and there was no sign of anterior uveitis OU and no residual hyphema. Iris heterochromia had resolved. Moderate posterior uveitis persisted OD with a temporal vitreous snowball. The disc was slightly hyperemic and the periphery of the retina had salt and pepper markings, consistent with RPE hypertrophy and hypotrophy. An OCT showed an epimacular membrane with vitreo-macular traction and foveal distortion. Topical prednisolone 1% four times a day ODand topical atropine 1% twice a day OD were started.
OD had 20/400 visual acuity with pinhole improvement to 20/125 2 weeks later. Vitreous cell activity was reduced with partial resolution of vitreous snowball. He was then lost to follow-up.


A 47-year-old man complained of poor balance for 1 month and was found to have a low sodium of 129 mmol/L. He was admitted elsewhere, and sodium was corrected with fluid restriction but this did not improve his imbalance. A neurological consultation suspected that his imbalance was secondary to neuropathy and started him on appropriate therapy. He was discharged shortly after. His inflammatory markers were elevated but this was not followed up.
Two days after discharge, he developed painful vision loss OD and diffuse joint and back pain. There was no history of prior eye surgery or trauma. Exam OD was notable for light perception vision without RAPD, neovascularization of the iris, and 1 mm hyphema and inflammation in the anterior chamber. Due to dense inflammation, there was no view of the fundus OD. B-scan revealed choroidal thickening and vitreous opacities representative of inflammation or hemorrhage OD. OS vision was 20/70 without pinhole improvement. There was no RAPD OS and slit lamp exam showed keratic precipitates and anterior inflammation. There was optic nerve edema OS. IOP OD was 10 mmHg and 11 mmHg OS. He was prescribed topical prednisolone drops 1% every 2 h OU and topical cyclopentolate 1% two times per day OU.
Blood tests were positive for HIV, RPR (1:128), and Treponemal antibody. Tuberculosis interferon, Angiotensin converting enzyme, ANA blood tests were negative. Given his constellation of symptoms neurosyphilis was suspected. Social history revealed that he was sexually active with multiple female partners in the past month and did not use condoms. He also had a history of past IV drug use and was currently smoking methamphetamine.
Lumbar puncture was also positive for Treponemal antibody. IV Benzylpenicillin 4 million units every 4 h was administered for 14 days on an inpatient basis. HIV screening during this admission was positive and he was started on highly active antiretroviral therapy.
Follow-up 3 weeks later was notable for hyphema resolution but persistent keratic precipitates. OD vision was greatly improved to 20/200. OS was 20/40 with dense posterior synechiae, cataract, and a fixed mid-position pupil. IOP 10 mmHg OD and 9 mmHg OS. There was no sign of active inflammation OU. Prednisolone and cyclopentolate were stopped. It was thought that he had a visually significant nuclear and cortical cataract, posterior synechiae, and pupillary membrane OD. Cataract surgery was performed OD. A month after cataract surgery, OD vision was 20/100 without pinhole improvement and exam revealed trace cell in the anterior chamber, vitreous pigment, and a mild epiretinal membrane with subtle edema on OCT. He was re-started on prednisolone 1% four times a day OD and referred to Retina. At 6 months from initial presentation, he was seen by Infectious Disease and HIV RNA was undetectable and his RPR had declined enough to be considered clinically cured of neurosyphilis. The patient was lost to Ophthalmology follow up and all efforts to contact him have failed.


A 62-year-old male with stage III prostate cancer undergoing treatment with leuprolide and radiation therapy presented with a one-week history of anorexia, night sweats, subjective fevers, and abdominal pain.
The patient was afebrile and hemodynamically stable in the emergency department. Physical examination was significant only for right-sided abdominal tenderness. Laboratory studies showed a mild leukocytosis (white blood cell count: 13.3 K/µL; reference range: 4.5-11.0 K/µL) with bandemia, anemia (hemoglobin: 8.5 g/dL; reference range [male]: 14.0-18.0 g/dL), and elevated alkaline phosphatase (alkaline phosphatase: 276 U/L; reference range: 20-140 U/L). Prostate-specific antigen was <0.01 ng/mL (reference range: 0.0-4.0 ng/mL). Bilirubin, alanine aminotransferase, and aspartate aminotransferase were within normal limits. Renal function studies were unremarkable. Urinalysis was negative for leukocyte esterase and nitrites. Correlation of the clinical history and physical examination findings was worrisome for an occult infection, prompting emergency department providers to obtain additional imaging.
An abdominal ultrasound demonstrated several poorly demarcated hypoechoic masses affecting the liver. A CT scan of the abdomen and pelvis with contrast was obtained to further characterize the lesions; this showed numerous peripherally enhancing, centrally hypoattenuating masses in liver segments II, III, and IV (Figure ). All lesions were new as compared to a CT scan from two months earlier.
The differential diagnosis included liver abscesses and cystic metastases. Blood, sputum, stool, and urine cultures were acquired, and the patient was started on intravenous ceftriaxone and metronidazole. A final needle biopsy of a lesion was obtained for pathologic examination.
Tissue cultures grew S. mitis. Infectious disease was consulted and recommended intravenous ceftriaxone and metronidazole. The patient’s symptoms gradually began to improve, and he was discharged in a stable condition after a two-week hospital stay. Daily infusions of intravenous ceftriaxone was continued on an outpatient basis for a duration of six weeks. The patient continued to follow up with the infectious disease clinic. Repeat CT scan of the abdomen and pelvis with contrast obtained one month after completion of antibiotic therapy revealed resolution of the abscesses (Figure ).


A 75-year-old non-diabetic male diagnosed with relapsed NSCLC on follow-up imaging for left lower lobectomy for early-stage lung cancer. Given his excellent performance status, he was deemed a candidate for chemotherapy plus immunotherapy and started on carboplatin, pemetrexed, and pembrolizumab. The interim scan showed a response to treatment. After three cycles of chemotherapy, he developed fatigue, severe nausea, and weight loss. His labs revealed neutropenia with absolute neutrophil count (ANC) of 300/mm3 after the third cycle. Carboplatin was held as a result, but pemetrexed and pembrolizumab were continued for a fourth cycle. Fatigue persisted, and he developed dyspnea on exertion. He was taken to the emergency department and found to be in atrial flutter with a heart rate of 154 bpm. A comprehensive metabolic panel revealed the patient to have a blood glucose of 642 mg/dl, with a serum bicarbonate level of 12 mEq/L and an anion gap of 20. Lactate was normal at 1.9 mg/dL, and creatinine mildly elevated at 1.37 mg/dL. A diagnosis of diabetic ketoacidosis was made, and he was started on intravenous fluids and an insulin drip. Further workup revealed increased levels of antibodies to glutamic acid dehydrogenase (anti-GAD), thyroid peroxidase (anti-TPO), and thyroglobulin autoantibodies (563 IU/mL). These findings were consistent with the diagnosis of T1DM and autoimmune thyroiditis and presumed to be an adverse effect of pembrolizumab therapy.
Intervention
Treatment with pembrolizumab and pemetrexed was held because of the occurrence of these serious adverse effects. He is on a subcutaneous insulin regimen to manage his T1DM. A three-week follow-up is planned, and if asymptomatic, pemetrexed only will be continued, with pembrolizumab being discontinued due to adverse events.


The patient was a 70-year-old male who was referred to our hospital to undergo an operation for an aneurysm of the aortic arch. He had slight hoarseness that was suspected of being caused by the aortic aneurysm. His medical history included dyslipidemia and hypertension. Preoperative computed tomography showed different-size multifocal lesions in the mediastinum from the anterior to the superior region with slight contrast enhancement, low-density areas equivalent to fat tissue, and spotty calcification (Fig. ). Laboratory data showed a slightly high level of LDL-cholesterol (216 mg/dL), triglyceride (170 mg/dL), and soluble IL-2R (496 U/ml). Other tumor markers, including carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), and human chorionic gonadotropin (HCG), were within the normal ranges. He had no history of trauma and was not on any anticoagulant drugs. In addition, angiography showed stenosis on the coronary artery, and head magnetic resonance imaging (MRI) showed an asymptomatic old cerebral infarction.
Because we suspected the tumors of being multiple thymoma or malignant lymphoma, we decided to remove the tumor for a definitive diagnosis and treatment. We performed total thymectomy followed by aortic arch replacement and coronary artery bypass under median sternotomy. During the surgery, we observed four lesions in the thymus with elastic hardness. One of the granulomatous masses was located at the caudal of the left lobe of the thyroid gland. The tumors were 4.2 × 2.6 × 1.7 cm, 2.3 × 2.3 × 1.4 cm, 2.6 × 2.6 × 2.4 cm, and 3.2 × 3.0 × 2.2 cm in size with yellowish-brown discoloration, and they were located on the left side, right side, top, and bottom of the thymic tissue (Fig. ). In addition, a microscopic examination of these tumors revealed a series of cholesterin crystals surrounded by multinucleated giant cells and histocytes, some of which had phagocytosed hemosiderin granules, findings that were consistent with a cholesterol granuloma (Fig. a). Osseous metaplasia and calcification were also observed in the tumors (Fig. b). The granuloma was adjacent to the remnants of thymic tissue, although there was no particular evidence showing that the thymic tissue had penetrated the granuloma.
Based on these findings, the pathological diagnosis of cholesterol granuloma in the thymus was made. The patient was discharged without any postoperative complications and was followed up for 2 months postoperatively without any recurrence.


A 73-year-old male presented with painless decreased visual acuity, floaters and flashes in the right eye for 2 weeks. The right eye did not have any previous history of trauma, surgery, cryotherapy or laser photocoagulation except for an uneventful cataract surgery 15 years ago. His left eye had undergone vitrectomy with retained silicone oil to treat retinal detachment for 8 months from another hospital. The left eye was now aphakic with retinal redetachment under the silicone oil, secondary glaucoma and band keratopathy. His medical underlying diseases were essential hypertension and hyperlipidemia. His systemic medications included amlodipine, losartan and simvastatin.
At presentation, best-corrected visual acuity (BCVA) was 0.6 logMAR and counting fingers in the right and left eyes, respectively. Intraocular pressure (IOP) was 14 mmHg in the right eye and 12 mmHg in the left eye. Ocular examination of the right eye showed normal conjunctiva and sclera, clear cornea, mildly shallow anterior chamber with no cell or flare and the eye was pseudophakic. The pupil was dilatable to 5 mm. Dilated fundus examination revealed corrugated inferior bullous retinal detachment with shifting of subretinal fluid (Fig. a). No definite choroidal detachment or a retinal break was identified with a wide-field contact lens. Optical coherence tomography (SPECTRALIS, Heidelberg Engineering, Heidelberg, Germany) of the macula showed subretinal fluid, a small juxtapapillary pigment epithelial detachment and intraretinal cysts (Fig. a and b). At this point, rhegmatogenous retinal detachment with a very small retinal break versus exudative retinal detachment were to be differentiated. The patient was then worked up for possible etiologies of exudative retinal detachment including choroidal inflammation, choroidal tumors and atypical central serous chorioretinopathy.
Ocular B-scan ultrasonography (Aviso, Quantel Medical, Clermont-Ferrand, France) demonstrated ocular wall thickening with peripheral choroidal elevation in the right eye. No tumors were identified and no subtenon fluid collection to suggest posterior scleritis was detected. The axial length measurement (IOL Master 500, Carl Zeiss Meditec, Jena, Germany) was 22.59 and 22.94 mm in the right and left eyes, respectively, which was not compatible with nanophthalmos. Fluorescein angiography (FA) (SPECTRALIS, Heidelberg Engineering) showed granular hyperfluorescence, consistent with window defects, at the mid-periphery and peripapillary areas. No dye leakage was detected to explain the subretinal fluid, which made central serous chorioretinopathy unlikely (Fig. ). Indocyanine green angiography (ICGA) (SPECTRALIS, Heidelberg Engineering) demonstrated diffuse early hypercyanescence especially in the posterior pole and superotemporal vortex veins that persisted to the late phase in the peripapillary area (Fig. , column a). FA and ICGA showed no evidence of chorioretinal inflammation, which made choroiditis such as sympathetic ophthalmia unlikely. Blood tests including complete blood count, blood chemistries, erythrocyte sedimentation rate, C-reactive protein, serological test for human immunodeficiency virus, venereal disease research laboratory test for syphilis, Treponema pallidum haemagglutination test, interferon gamma assay for tuberculosis, antinuclear antibodies test and antineutrophil cytoplasmic antibodies test were all within normal limit. The chest x-ray was also performed and showed no pulmonary infiltration. After excluding the infectious etiologies, 1 mg/kg/day of oral systemic steroid was challenged to the patient for 7 days without clinical responses. UES was now high in the differential diagnosis. The ultrasound biomicroscopy (UBM) (Aviso, Quantel Medical) was then performed and revealed edematous thickening of the anterior choroid and thickening of the anterior sclera measuring up to 1.26 mm (Fig. ), leading to the diagnosis of UES (normal scleral thickness at the corneoscleral limbus is 0.53 ± 0.14 mm []).
Partial thickness sclerectomy and sclerotomy was then performed based on the technique described by Gass, 1983 []. In brief, two-thirds thickness scleral flaps of 5 mm × 7 mm were created centering at 2 mm anterior to the equator in each of the 4 quadrants. Full thickness sclerotomy (scleral window) of 2 mm × 2 mm was then made on each of the remaining scleral beds under the flaps. The scleral flaps from inferonasal and inferotemporal quadrants were excised and sent for histological examination.
At 2-week post-operation, the BCVA improved to 0.2 logMAR in the right eye with the IOP of 16 mmHg and the subretinal fluid progressively reduced. At 4 months, the retina was completely attached, revealing a typical leopard spot pattern described in UES (Fig. b, c and d). One year after the surgery, follow-up ICGA revealed less choroidal hyperpermeability (Fig. , column b). Histologic findings (Fig. ) of the excised sclera revealed neither inflammation nor disorganization of collagen fibers. Special stains including periodic acid–Schiff, periodic acid–Schiff–diastase, alcian blue, alcian blue with hyaluronidase, mucicarmine, congo red and reticulin showed no demonstrable proteoglycans or other abnormal substance deposits.


A 25-year-old young woman presented to the University of Gondar Hospital, Northwest Ethiopia, with progressive difficulty of keeping balance of three-year duration and change in voice (slurring of speech) and tremor of hands of six-month duration. She had no visual disturbance, weakness of extremities, or bladder or bowel problem. She had no memory loss or epileptic fits. Her younger sister has been wheel-chaired due to neurologic problem. No preceding head injury or excess alcohol intake. Serology for HIV infection was negative. There was no history of yellowish discoloration of eyes, urine color change, or abdominal distension.
On physical examination, she was nourished, conscious, and oriented. Vital signs were within normal limits and stable. She had pink conjunctivae and nonicteric sclerae. Her lungs, heart, and abdomen examinations were unremarkable. On neurologic examination, she was oriented in time, place, and person. There were no cranial nerve abnormalities. No motor or sensory deficits occurred. Tandem walk and heel-to shin tests were poorly performed. She had dysarthria (slurred speech) and intention tremor of hands. Then, diagnosis of ataxic disorder due to multiple sclerosis was made at initial evaluation. Diagnosis of Wilson's disease was considered by the neurologist by pointing out the Kayser–Fleischer ring on both eyes, after the radiologist reported the possibility of Wilson's disease on MRI imaging.
A laboratory examination revealed hemoglobin 15 gm/dl (normal, 12–18 gm/dl), total leukocyte count 5,200/μl (normal, 4000–11,000/μl; granulocyte 54%, lymphocyte 35%), platelet count 87,000/μl (normal, 150,000–450,000/μl), and ESR 01 mm in first hour. Serum biochemical tests were normal. Serum tests for ANA and RF were negative. The serologic test for HIV, hepatitis B, and hepatitis C infections was negative. Abdominal ultrasound examination revealed the coarse echotexture liver with surface irregularity. Axial T2-weighted MRI images showed bilateral hyperintensities on basal ganglia and thalamus (). Serum ceruloplasmin level by immunoturbidimetry and 24 hr urinary copper content by inductively coupled plasma-mass spectrometry (ICP-MS) were determined in the International Diagnostic Laboratory in Addis Ababa, Ethiopia, to support the imaging diagnosis. Serum ceruloplasmin concentration was reduced (<10 mg/dl), and 24 hr urinary copper excretion was increased (142.2 μg/24 hrs). In sum, the clinical signs, biochemical tests, and imaging findings met diagnostic criteria for Wilson's disease (K-F rings present, score 2; mild neurologic symptoms, score 1; serum ceruloplasmin level <10 mg/dl, score 2; urinary copper content >2 × ULN, score 2; diagnosis of Wilson's disease established if score ≥4) (Tables and ).
Global Assessment Score (GAS) for WD was determined to quantify burden of disability using domains of liver (scale 0–5), cognition and behavior (scale 0–5), motor (scale 0–5), and osseomuscular (scale 0–5) []. The patient scored L3C0M2O0 at time of diagnosis. Then after, she was started on D-penicillamine, 300 mg, po, daily, and dose escalated by 300 mg weekly, to reach a target dose of 900 mg, po, daily. She was as well started on zinc sulphate, 110 mg, po, twice daily, and pyridoxine 25 mg, po, daily, and advised to avoid copper-rich diet. Then, the patient was referred to the Neurology Clinic, Tikur Anbessa Hospital, Ethiopia, for close follow-up. Screening of family members for Wilson's disease was recommended.


A 22-year-old, wheel-chaired, young woman presented to the University of Gondar Hospital, Northwest Ethiopia, with progressive weakness of proximal muscles (difficulty to go upstairs and stand from toilet, followed by difficulty of combing hair, and at last unable to stand) of 5-year duration and unable to keep balance of 3-year duration. She has been wheel-chaired in the last six months due to neurologic problem. She had been transiently incontinent to urine. She was treated with high-dose prednisolone (60 mg, po, daily) for six months with presumptive diagnosis of inflammatory myopathy but had no improvement. She had no memory loss or epileptic fits. Serology for HIV infection was negative. There was no history of yellowish discoloration of eyes, urine color change, or abdominal distension.
On physical examination, she was undernourished, conscious, and oriented. Vital signs were with in normal limits and stable. She had pallor of conjunctivae and nonicteric sclerae. Kayser–Fleischer rings were visible with naked eye. Her lungs, heart, and abdomen examinations were unremarkable. On neurologic examination, she was oriented in time, place, and person. No cranial nerve abnormalities occurred. She had proximal muscle weakness and atrophy on both upper and lower extremities. Deep tendon reflexes were variable. Tandem walk was difficult to perform due to weakness. She had head titubation and intention tremor of hands. Finger-to-nose was poorly performed. Diagnosis of ataxic disorder and myopathy due to Wilson's disease was considered after confirmed diagnosis of prior case. Laboratory investigations including complete blood count, biochemical tests, copper studies, and brain MRI were requested.
A laboratory examination revealed hemoglobin 8.6 gm/dl (normal, 12–18 gm/dl), total leukocyte count 3,700/μl (normal, 4000–11,000/μl; granulocyte 57%, lymphocyte 30%), and platelet count 137,000/μl (normal, 150,000–450,000/μl). Serum biochemical tests were normal. Serum tests for ANA and RF were negative. The serologic test for HIV, hepatitis B, and hepatitis C infections was negative. Abdominal ultrasound examination revealed the coarse echotexture liver with surface irregularity. Axial T2-weighted MRI images showed bilateral hyperintensities on basal ganglia, thalamus, and brain stem. “Face of the giant panda” in the midbrain was spotted on the MRI image (). Serum ceruloplasmin level was reduced (10.5 mg/dl), and 24 hr urinary copper content was increased (110.5 μg/24 hrs). In sum, the clinical signs, biochemical tests, and imaging findings met diagnostic criteria for Wilson's disease (K-F rings present, score 2; severe neurologic symptoms, score 2; serum ceruloplasmin level = 10.5 mg/dl, score 1; urinary copper content >2 × ULN, score 2; diagnosis of Wilson's disease established with score ≥4) (Tables and ). The global assessment score (GAS) was L3C0M4O4 at time of diagnosis. Then after, she was started on D-penicillamine, 300 mg, po, daily, and dose escalated by 300 mg monthly, to reach a target dose of 900 mg, po, daily. She was as well started on zinc sulphate, 110 mg, po, twice daily, and pyridoxine 25 mg, po, daily, and advised to avoid copper-rich diet. Then, the patient was referred to the Neurology Clinic, Tikur Anbessa Hospital, Ethiopia, for close follow-up.


An 11-year-old boy with hemoglobin SS sickle cell disease (SCD) was referred to our hospital for further treatment of CTEPH. He had a history of multiple pain crises, acute chest syndrome, and acute ischemic strokes at ages 3 and 7 years. His SCD was further complicated by moyamoya syndrome, for which he underwent encephalodurosynangiosis at age 7 years. His hypercoagulability workup had been negative for antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, plasminogen deficiency, and anticardiolipin antibodies.
Approximately 10 months before his referral, routine screening transthoracic echocardiogram (TTE) revealed a right atrial (RA) thrombus thought to be related to his Broviac central venous catheter, which had been used for exchange transfusions. He was started on enoxaparin and his Broviac catheter was replaced. TTEs over the ensuing months demonstrated persistent RA thrombus without change in size, with normal RV pressure and normal biventricular systolic function.
Seven months later, the patient was electively admitted to the referring institution in anticipation of a bone marrow transplant (BMT), at which time routine TTE showed an elevated RV systolic pressure (58 mmHg plus the RA pressure), a change from his previous echocardiograms. CT scan of the chest at that time revealed multiple bilateral lower lobe and left upper lobe pulmonary emboli. Clinically, he reported mild dyspnea on exertion and exercise intolerance for several weeks. Medical management was started with bosentan and the patient's enoxaparin dose was increased.
Follow-up TTE performed 3 months later showed severe PH, with RV systolic pressure of 90 mmHg plus the RA pressure and a corresponding blood pressure of 108/52 mmHg. This raised suspicion for CTEPH, which was supported by a ventilation-perfusion (VQ) scan showing multiple areas of wedge-shaped mismatched perfusion defects consistent with chronic bilateral thromboembolic disease and secondary PH consistent with CTEPH. The following day, right heart catheterization demonstrated pulmonary arterial pressure of 80/35 mmHg with a mean of 52 mmHg, pulmonary capillary wedge pressure of 14 mmHg, cardiac index of 5.7 L/min/m2, and pulmonary vascular resistance index of 6.6 WUm2. Pulmonary angiography revealed multiple areas of abrupt tapering of the pulmonary arteries, confirming the diagnosis. The patient was switched from bosentan to macitentan and riociguat, and he was referred to our center for PTE.
At admission, his blood pressure was 116/72 mmHg, heart rate was 114 beats per minute, respiratory rate was 18 breaths per minute, and oxygen saturation was 97% on room air. The result of the physical examination was unremarkable. Quantitative hemoglobin S was abnormal at 13.5%, and NT-ProBNP was elevated at 880.0 pg/mL (normal range, 10.0–242.0 pg/mL). The results of the remaining laboratory tests, including coagulation tests, were normal.
He successfully underwent bilateral PTE and removal of a calcified organized thrombus from the right atrium () without reported intraoperative complications. Post-operative transesophageal echocardiography demonstrated an estimated RV systolic pressure of 32 mmHg plus the RA pressure in the setting of a systolic blood pressure of 110 mmHg, with mildly decreased RV function. Central venous pressure was maintained under 8 mmHg with a furosemide infusion to avoid reperfusion injury. PH medications were discontinued at the time of surgery. Ten days after the procedure, the patient was completely asymptomatic with normal oxygen saturation and was discharged home on long-term warfarin. Four months later, he successfully underwent BMT, after which he had weekly TTEs to monitor for the development of PH (). As of 6 months following surgery, the patient has remained clinically asymptomatic without echocardiographic evidence of RV hypertension based on tricuspid regurgitant jet and systolic septal position.


A 62-year-old man presented with vision loss in his left eye after blunt trauma 2 weeks ago. He had undergone a discontinued PPV procedure because of inadequate fundus view at a local hospital 5 days ago. The vision in his left eye was light perception. Ocular examination showed conjunctival injection, complete hyphema associated with corneal blood staining. The intraocular pressure (IOP) was 11 mmHg. B-scan ultrasonography revealed retinal detachment and choroidal detachment. He was scheduled to undergo an urgent vitrectomy. After the hemorrhage in the anterior segment was cleared by irrigation, the lens was not seen, and the posterior segment could not be clearly viewed due to the corneal opacity. The technique of the modified deep anterior lamellar corneal dissection was performed. A shallow groove was gently made using a 7-mm trephine. Then a 15-degree slit knife was used to increase the incision depth and separate the deep anterior lamellar corneal tissue from the stroma anterior to the underlying Descemet membrane (DM) by cutting along the groove for about 3/4 circumference, leading to a corneal flap (Fig. a).The remaining deep stromal fibers were carefully peeled off using a forcep with the help of the retroillumination from a 25 gauge fiber optic illumination probe going through the peripheral anterior chamber (Fig. b). Finally, a moderately transparent corneal bed comprised of DM and a fine layer of deep stroma offered a clear enough view for pars plana vitrectomy (Fig. c). The dense vitreous hemorrhage was progressively removed, revealing a total retinal detachment in the shape of a closed funnel (Fig. d). Following the removal of epiretinal and subretinal proliferative fibrous membranes and peripheral retinotomy, the retina was reattached with application of perfluorocarbon liquid. Endolaser and silicone oil (Oxane 5700; Bausch & Lomb, Rochester, NY, US) tamponade were performed. Finally, the corneal flap was stitched back with interrupted 10–0 nylon (Video 1). Postoperatively, the cornea gradually became transparent, leading to a clear fundus view without impediment within 3 months (Fig. e). The silicone oil was removed 3 months after the surgery with a flat retina and improvement of vision to counting fingers (Fig. f). The IOP was 10 mmHg. The suture was removed 4 months postoperatively. The eye remained stable at the 6-month follow up.


A 45-year-old man suffered a recurrent retinal detachment associated with corneal endothelial decompensation in the right eye from a cataract combined with complicated retinal detachment surgery and subsequent repeat vitrectomies and silicone oil tamponade for complicated retinal detachment within 2 years. On examination, the vision was light perception in his right aphakic eye. The corneal stroma was entirely edematous while the epithelium showed intact. B-scan ultrasonography revealed retinal detachment (Fig. a). Poor visibility through the cloudy cornea precluded fundus view (Fig. b). The deep anterior lamellar dissection was also performed before vitrectomy. After the separation of anterior lamella as described above, the remaining corneal tissue could not provide adequate view of fundus. We thought the dissection was not deep enough because of the relatively thicker cornea. Then, the big-bubble technique was used to separate the posterior stroma from the DM (Fig. c). The deeper lamellar flap was also created and preserved. With good visualization of the intraocular structure through the transparent DM (Fig. d), retinal repair was performed with the application of retinectomy. After retinal reattachment and silicone oil tamponade as case 1, the two layers of corneal flap were sutured back (Fig. e). The cornea remained cloudy, but the retina was confirmed as attached by ultrasonography postoperatively. Three months later, the original corneal flaps were dissected again and the silicone oil was removed after intraoperative reconfirmation of retinal attachment. The opaque corneal flaps were sutured back. The eye was stable and asymptomatic within 4-month follow up (Fig. f). The vision was light perception and the IOP was 24 mmHg. Because the improvement of vision wouldn’t be possible, further surgery of corneal transplantation was not considered.


A 37-year-old man was admitted by emergency with a headache, nausea, vomiting, fever, numbness of the left cheek and upper limb for 10 days which had aggravated in 1 week. Physical examination found sanity, poor mental state, drowsiness, cyanosis, clubbing, low appetite, nuchal rigidity, shallowing left nasolabial fold, and loll left and left limb muscle force at grade IV, with no other cranial nerves deficit. No special medical history was found. No other infection was found. Preoperative blood bacteria culture proved negative. Hemoglobin (HGB) was 213 g/L, and RBC was 6.89 × 1012/L. Arterial blood gas analysis revealed a pH of 7.41, PCO2 is 33 mmHg, PO2 is 66 mmHg, oxygen saturation is 93%, and HCO3− is 20.9 mmol/L on room air. Computed tomography (CT) scan of the brain indicated a low-density shadow in the right frontal lobe with the edge enhancing. Brain MRI showed a 33 mm × 41 mm × 40 mm ring-enhanced capsule in the right frontal lobe with severe perilesional edema which leads to the midline shifting to the left side, and the right ventricle was metamorphose (Fig. ). Chest x-ray revealed a high-density nodule with an irregular shape in the right lower lung. To make further diagnosis, pulmonary artery computed tomography angiography (CTA) which is a diagnostic criterion of pulmonary AVF was performed to confirm AVF (Fig. , ). To avoid brain hernia for high intracranial pressure, craniotomy for the lesion and decompressive craniotomy were performed. During the operation, the lesion capsuled by a green wall was totally resected and there was a deep yellow abscess inside. The analysis on germiculture and sensitive test of the surgically removed brain abscess showed that it was microaerophilic streptococcus infected. After the operation, we used intravenous vancomycin hydrochloride (1000 mg q12h) according to the drug susceptibility test result. We suggested him to have an antibiotic therapy for 4 weeks and therapeutic embolization of PAVF. One month later, embolization using Amplatzer vascular plugs was performed on him (Fig. –). The postoperative symptoms of the patient were obviously improved. According to the Curacao criteria, which is the diagnosis of hereditary hemorrhagic telangiectasia, [] (Table ), the patient’s family history and symptoms accord with one criteria that suggest underlying HHT. After embolization, the patient’s blood oxygen saturation and hemoglobin returned to normal.


A 60-year-old Asian woman on siltuximab (11 mg/kg) infusion every three weeks for biopsy-proven cutaneous and systemic IMCD (plasma cell type) presented with recent onset of cough. However, she was afebrile and had no other constitutional symptoms.
Her disease onset began 14 years earlier. She presented with skin lesions as well as a persistent cough and hemoptysis. A CT scan only revealed mild bronchiectasis of her right upper lobe and right lower lobe of her lung with bronchial wall thickening; in addition, heterogeneous areas of nodular and linear interstitial thickening with ground-glass opacification were observed in the right upper lobe and the right middle lobe. Her bronchoscopy was normal, and the bronchoalveolar lavage was negative for bacteria, fungi and mycobacteria.
Her condition remained undiagnosed for another 11 years. Biopsies of her skin lesions from the back and groin then showed a polytypical plasma cell infiltrate with B-cell hyperplasia. The kappa to lambda staining ratio was normal (3:1), and light chain restriction was not demonstrated. The pathological diagnosis was consistent with Castleman disease, plasma cell variant. HHV-8 was negative and she had no diagnostic features of POEMS syndrome.
She was then referred to our institution and we planned to start siltuximab. At that time, she had a cough, mild hemoptysis, and numerous hyperpigmented brown patches and plaques on her lower chest and abdomen, bilateral flanks, back and buttocks, axillae and groin, and proximal arms and legs (Figure ). She told us that new skin lesions appeared every couple of weeks.
Biopsies were performed from plaques on her right axilla and right thigh (Figure ). They were again consistent with Castleman disease, showing a cutaneous B-cell infiltrate with germinal center formation and polytypic plasma cells; the kappa to lambda evaluation also revealed polytypic plasma cells. Staining for HHV-8 was again negative.
A baseline positron emission tomography/computed tomography (PET/CT) scan showed mildly enlarged lymph nodes in the neck, chest and abdomen with mildly elevated fluorodeoxyglucose activity. A right submental lymph node biopsy also showed Castleman disease. Pertinent laboratory study results included an elevated erythrocyte sedimentation rate, anemia (hemoglobin = 11.5 g/dL) and thrombocytosis (platelets = 578,000/µL).
She was started on siltuximab at a dose schedule of 11 mg/kg intravenously every three weeks. Within three months, her skin lesions had all flattened and several began to fade. No new lesions appeared. Her cough and hemoptysis resolved. Follow-up PET/CT scans after three and six months showed improvement in imaging abnormalities.
After nine months of treatment, however, her cough recurred. She had no fever and no other constitutional symptoms such as arthralgias, myalgias, fatigue, night sweats or weight loss. Her skin lesions were continuing to diminish. Her staging PET/CT scan showed new patchy infiltrates in the right lung (Figure ).
The principal differential diagnoses of her pulmonary symptom (cough) and radiographic findings included a recurrence or progression of her Castleman disease, a new pulmonary tumor and an afebrile pneumonia. An infectious etiology was favored, and she was empirically treated with levofloxacin 750 mg daily for seven days.
All of her pulmonary symptoms had resolved when she was seen at her follow-up visit two weeks after starting oral antibiotics. Her staging PET/CT scan three months later showed disappearance the patchy infiltrates that had been observed on the prior PET/CT scan. Correlation of the clinical features and radiographic studies established the diagnosis of an afebrile pneumonia without any associated constitutional symptoms.
She has been maintained on her siltuximab every three weeks. Her IMCD continues to improve. She has not had another episode of cough.


Mr. C was a 24-year-old university-educated single male with no prior history of psychosis and no family history of mental illness. He presented to the emergency department accompanied by his parents due to multiple worsening somatic delusions. According to his parents, he became preoccupied with his physical appearance following an increase in the dosage of his isotretinoin from 40 mg/day to 80 mg/day. Mr. C believed that his face was disfigured after using Tobradex eye drop. He believed the eye drop had pooled in his nose, damaged his throat, and disfigured his face. He alleged that his forehead and teeth had shifted and that his tongue had atrophied. He denied spending a lot of time in front of a mirror; although, when he looked in the mirror, he saw a distorted face. He later complained of further symptoms including muscle atrophy, weakness, and trouble walking, despite a normal gait.
He denied symptoms of depression or anxiety. He denied auditory, visual, and tactile hallucinations as well as suicidal and homicidal ideations. There was no history of substance use, including cannabis and alcohol. All of the investigations, including complete blood count, electrolytes, blood glucose, thyroid function tests, liver enzymes, and renal function tests, were normal. His drug urine screen was negative for illicit substances, including benzodiazepines. Computed tomography (CT) of the head was normal. The electroencephalogram (EEG) was reported within normal limits as no focal abnormalities nor epileptic activities were identified.
In Mr. C's case, the absence of any prodromal symptoms, previous psychiatric history, or family history of mental illness made a primary psychotic disorder unlikely. Furthermore, the temporality of his symptoms coincided with the doubling of the isotretinoin dose from 40 mg to 80 mg daily. Additionally, there is a biological gradient or dose-response relationship, meaning that as the dose of isotretinoin increases, so does the potential of developing psychiatric symptoms, such as psychosis.
Based on his symptoms, he was given a diagnosis of delusional disorder, somatic subtype, as he had multiple somatic delusions for longer than 1 month, but his functioning was not markedly impaired, and his behaviour was not obviously bizarre. Somatic symptom disorder was considered as a differential diagnosis; however, Mr. C's concern about his somatic symptoms did not reflect a fear of underlying illness. The isotretinoin was discontinued, and he was started on quetiapine 100 mg orally at bedtime and was compliant with medication. Patient's symptoms resolved two weeks following the discontinuation of the isotretinoin, and the quetiapine was similarly discontinued after two months. Patient was discharged from psychiatric care to his family physician following a four-month period of sustained remission from the date of his discharge from his index psychiatric admission.