A 45-year-old previously healthy white man presented with multiple fragility fractures over 2 years, as well as pain and functional deficits eventually rendering him nonambulatory. He carried no previously diagnosed medical history, although he was a former smoker with a 13 pack-year smoking history. His family history was notable for grade 1 chondrosarcoma in his mother. He initially presented to an orthopedic clinic with foot pain and hip pain after starting an exercise program. Initially, he was counseled to participate in physical therapy; however, he continued to develop progressively disabling pain. Over the course of 8 months, he was diagnosed with bilateral metatarsal and subtrochanteric femur fractures on imaging.
A local endocrinologist was consulted based on suspicion for secondary causes of bone loss. His laboratory tests were notable for a low phosphorus at 2.1 mg/dL (2.7–4.5), elevated alkaline phosphatase (ALP) at 155 IU/L (34–104), elevated PTH at 211 pg/mL (12.0–72.0), low 25OHD, and 1,25(OH)2D3 at 27 ng/mL (30–80) and 12 pg/mL (20–80), respectively. However, calcium was normal at 8.8 mg/dL (8.4–10.4). Serum protein electrophoresis revealed no evidence of monoclonal gammopathy. Additional studies included a low free testosterone at 4.4 ng/mL (5–21) and luteinizing hormone at 2.2 mIU/mL (3.0–10.0). Other pituitary hormone levels and brain MRI were unremarkable.
Vitamin D3, calcitriol, phosphate, and testosterone were prescribed. Testosterone was discontinued 6 months later, after developing a venous thromboembolism of the left common femoral, superficial femoral, and popliteal veins, and pulmonary embolus of the left pulmonary artery. Workup for genetic causes of hypercoagulability was negative; he ultimately received anticoagulation for a year with rivaroxaban. Incidental rib fractures on a chest X-ray at the time prompted a three-phase 99Tc-MDP bone scan, revealing multiple sites of uptake: ribs, scapulae, sternum, thoracolumbar spine, sacrum, bilateral ankles, and feet (Fig. .
Laboratory tests showed ongoing phosphate wasting, despite compliance with calcitriol 0.25 μg/d, cholecalciferol 5000 IU/d, and phosphorus 2250 mg/d in divided doses. Calculated tubular reabsorption of phosphate was 64% (>80%) and renal tubular maximal phosphate to glomerular reabsorption rate (TmP/GFR) was 1.74 mg/dL (2.5–4.5), indicating inappropriately low Pi reabsorption. Of note, it is unclear if the patient was taking phosphorus supplementation at the time of these measurements. Urine 24-hour calcium was 244.8 mg (100–300). Testing for causal mutations in hypophosphatemic rickets and osteogenesis imperfecta was negative. Serum C-terminal FGF23 level was tested based on concern for an acquired cause of hypophosphatemia such as TIO, and was within the reference range at 138 RU/mL (LabCorp ELISA 44–215; LabCorp, Burlington, NC, USA). At this point, 3 years after symptom onset, he was referred to our academic endocrinology practice for further workup of possible secondary causes of his phosphate wasting. His examination was remarkable only for an elevated BMI of 35, diffuse muscle and bone tenderness to palpation without evident deformities, and requirement for an ambulation-assist device. We interpreted his normal serum FGF23 level as inappropriately high for his degree of hypophosphatemia, prompting a search for a suspected TIO locus, which was further considered based on rapid clinical deterioration in a previously healthy patient. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) exhibited a hypermetabolic focus at the left suprapatellar recess, which corresponded with a small 1.7-cm mass that had previously been seen on CT 2 years prior but thought to be clinically insignificant because of its benign appearance (Fig. ). MRI demonstrated stability in size over this time period with near homogenous enhancement suggestive of a benign process; signal intensity was slightly higher than muscle with punctate areas showing low signal foci, potentially indicative of a degree of mineralization (Fig. ). Serum C-terminal FGF23 measurement was measured with LabCorp ELISA again, and was now elevated at 289 RU/mL (44–215).
Biopsy showed a phosphaturic mesenchymal tumor (Fig. ) and chromogenic in situ hybridization (Mayo Clinic, Rochester, MN, USA) was positive for FGF23 mRNA, confirming this site as a likely TIO locus (Table ). After surgical resection of the tumor, serum C-terminal FGF23 declined to <50 RU/mL 1-week postoperative and was 90 RU/mL 3 weeks later (Mayo <180 RU/mL). Phosphorus and 25OHD level were rechecked at 1 month postsurgery and found to have normalized, permitting discontinuation of calcitriol and phosphorus. DEXA 8 weeks after surgery showed marked improvements, with lumbar spine T score increasing from −2.8 to −1.0 (BMD +64.29%) and femoral neck T score from −1.9 to −1.4 (BMD +26.32%). The patient also experienced significant improvement in physical function and pain after his operation.


This is the case of a 30-year-old male that was sent by his primary care physician (PCP) for evaluation of abdominal distention and left-sided neck swelling. The patient had cerebral palsy and was a poor historian. His sister took him to his PCP because he was not eating well, losing weight, and had some shortness of breath. The patient’s PCP noticed an abdominal mass as well as a left-sided neck mass. Neither the patient nor his sister was aware when these symptoms appeared or how long they had been there. The patient had been having normal bowel movements; no abdominal pain, nausea, vomiting, or diarrhea; no chest pain; no fever, chills, cough, or any other complaints.
On physical examination, he was tachycardic and cachectic with bitemporal wasting. On the left side of the neck, there was a solid golf ball size mass, which was non-movable. The chest evaluation revealed clear breath sounds and tachycardia. Abdominal examination revealed distention with a large palpable grapefruit-sized mass. There was some guarding but no rebound. Genitalia examination showed a hard, non-tender mass of the right scrotum.
Laboratory analysis revealed a white blood cell count of WBC 14.08 K/mm3, hemoglobin 10.1 gm/dL, a normal basic metabolic panel, aspartate transaminase (AST) 241 units/L, and alkaline phosphatase 1033 unit/L. We decided to add a beta-hCG because of the testicular mass. It was elevated at 5692 mIU/ml.
Computed tomography (CT) scans of the neck, chest, abdomen, and pelvis showed a large left neck mass (8.6 cm x 4.5 cm) with mediastinal lymphadenopathy versus metastatic lesions; multiple pulmonary nodules and masses; multiple liver and splenic lesions with retroperitoneal lymphadenopathy; large pelvic mass that extends from the level of the liver to the pelvic inlet (17 cm x 13 cm); large retroperitoneal mass that extends from the diaphragmatic hiatus to the aortic bifurcation (19 cm x 10 cm) resulting in mass effect to the abdominal viscera and vasculature; and a pancreatic head mass (5.9 cm x 3.7 cm) (Figures -).
A testicular ultrasound showed no torsion but a solid mass on the right testicle, which was also noted on CT. The patient was admitted to the hospital and underwent orchiectomy. Biopsy of the left neck showed metastatic undifferentiated necrotizing malignant tumor consistent with germ cell tumor with features favoring embryonal carcinoma component. Biopsy of the right testicular mass showed embryonal carcinoma with abundant necrosis and small foci suggestive of yolk sac component. The spermatic cord margin of resection was positive for tumor. The tunica vaginalis was uninvolved. Lymphovascular invasion was present. AFP level was high at 12,200 ng/ml. The patient was diagnosed with stage IV non-seminomatous germ cell tumor (NSGCT) and received four cycles of cisplatin chemotherapy.


A 26-year-old man presented to the emergency department with penile pain and bruising after accidental trauma during intercourse one hour prior to arrival. He reported immediate pain and bruising with detumescence within minutes. Exam was revealing for eggplant deformity of the penis with soft dorsal ecchymosis and mass felt extending into the scrotum ().


A 72-year-old male with diabetic polyneuropathy presented to the ED with a chief complaint of chest pain two days after sustaining a flame burn while cooking. His vital signs were stable and his physical exam revealed a deep partial-thickness burn over the majority of his right pectoralis extending across midline to the left sternal border (). The patient reported severe thoracic pain (10/10) unrelieved with oral therapy consisting of NSAIDs and acetaminophen at home.
After obtaining informed consent, bilateral SABPs were performed in the manner described by Blanco et al. The anesthetic dose was calculated based on the patient’s weight of 66 kilograms (kg) and recommended maximum dose of 3 milligrams (mg)/kg ropivacaine. This yielded a maximum of 20 milliliters (mL) of 1% ropivacaine (10mg/mL) total for both SABPs, or 10 mL per side. An additional 5 mL of 1% lidocaine with epinephrine was added to each SABP to prolong the effect of the block and reduce the systemic absorption of ropivacaine.
The patient was positioned in the left lateral decubitus position with right arm overhead for the right-sided block. A high-frequency 10-5 megahertz linear transducer was used to locate the third rib in cross section in the mid-axillary line. Superficial to the rib lies the SA, which is deep to the latissimus dorsi (LD) (). The targeted lateral cutaneous branches of the intercostal nerves at thoracic vertebral levels three to nine (T3–T9), are located in the fascial plane separating the SA and LD muscles. Anesthetic spreads in the fascial plane above and below the level of injection to the lateral cutaneous branches of the thoracic intercostal nerves. Although anesthetic will affect dermatomes above and below the site of injection, it is necessary to adjust the injection site based on the dermatome level. We recommend injecting just above the superior level of injury, targeting the level above the dermatome in case of miscounting the ribs. In this patient, whose burns were located in the T2-T5 dermatomes, we injected at the T2 dermatome above the third rib at the mid-axillary line.
After sterilizing and anesthetizing the skin, an in-plane technique was used to inject the 15-mL mixture of ropivacaine and lidocaine with epinephrine between SA and LD muscles () following hydrodissection with 10 mL of normal saline. The same process was repeated on the patient’s left side. The injected ropivacaine and lidocaine spreads along the fascial plane above and below the site of injection, a process facilitated by hydrodissection with 10mL of normal saline before and after anesthetic administration. Thus, it is not necessary repeat injections at each thoracic vertebral level to achieve analgesia across the chest wall.
Five minutes after the initial injection, the patient reported significant analgesia over his right chest, and 20 minutes after the termination of the procedure he was able to sleep comfortably. The patient reported no discomfort during the injection process and experienced no side effects. A local burn center recommended admission for treatment with silver sulfadiazine and fluid resuscitation; when the patient was interviewed on hospital day two, he reported the SABP took approximately 20–30 minutes to take full effect and lasted for an estimated 15–18 hours. He ultimately required two doses of 2 mg intravenous morphine at approximately 30 hours and 35 hours after his SABP. His only other medications were acetaminophen 500 mg orally every six hours, ibuprofen 600 mg orally every six hours, and home medications gabapentin and trazodone. The patient was discharged in stable condition on hospital day two.


A 72 years-old woman referred to Piacenza Hospital in September 2019 due to fatigue and dyspnea. Complete blood count (CBC) showed severe macrocytic anemia with increased reticulocyte count (Hb 8.3 g/dl, MCV 97,2 fL, reticulocyte 180/1,000 RBC) and abnormal hemolysis tests (LDH 445 U/L, total/direct bilirubin 2.54/0.32 mg/dl) with low haptoglobin levels (<1 mg/dl). Direct antiglobulin test (DAT) detected IgG and C3. Bone marrow biopsy excluded an underlying lymphoproliferative disease and autoimmunity tests were negative. Warm autoimmune hemolytic anemia (AIHA) was diagnosed and, after failure of steroid treatment, four successful courses of iv Rituximab 375 mg/m2/week were undertaken. Hemoglobin levels promptly rose up to 11 g/dl and remained stable after steroid tapering to prednisone 5 mg/day. On March 13, 2020 the patient presented with fever, dyspnea, hypoxia (SaO2 94%), diarrhea and marked fatigue: she underwent a RT-PCR assay for Sars-CoV-2 from upper respiratory-tract swab which resulted positive and she performed a CT scan showing bilateral interstitial pneumonia leaving 75% visually well aerated lung (%V-WAL) (). After admission, the hemolytic process flared, causing severe symptomatic anemia (Hb 6.6 g/dl, MCV 90 fL, reticulocyte 88/1,000 RBC, LDH 430 U/L, total and direct bilirubin 1.56/0,44 mg/dl, haptoglobin <1 mg/dl) (). Virological investigations for EBV, CMV, VZV, Parvovirus B-19, and HIV resulted negative. Therapy with hydroxychloroquine (loading 400 mg/bid, then 200 mg/bid/6days) and darunavir-cobicistat 800/150 mg for 7 days was started associated with prednisone 1 mg/kg. The patient was maintained on low-flow oxygen therapy for 7 days and received two red-blood-cell Units. On 14th April, after progressive tapering of steroid treatment, Sars-CoV-2 nasopharyngeal swab was negative, fever and dyspnea were absent, hemoglobin was 12.5 g/dl, reticulocyte count was 17.9/1,000 RBC, and she was discharged.
On April 26st she was re-admitted to hospital for a relapse of hemolytic anemia, with increasing LDH (534 UI/L), transaminases (GOT 310 UI/L, GPT 486 UI/L), decreasing hemoglobin (8.3 g/dl) levels and decreasing lymphocyte (830/μl) and eosinophil (0/μl) count (). An immunosuppressive treatment cycle with azathioprine was started. The patient was asymptomatic for respiratory symptoms, but her Sars-CoV-2 nasal swab turned-out to be again positive.


A 56 years-old man with silent previous unremarkable medical history was admitted to hospital on March 21st due to fever >38°C, dyspnea, and vomiting. His upper respiratory tract Sars-Cov-2 sample was positive, and chest CT scan showed mild COVID-19 bilateral interstitial pneumonia leaving 95% visually well aerated lung (%V-WAL) (). He was hospitalized and treated with hydroxychloroquine (loading 400 mg/bid, then 200 mg/bid/6days) and darunavir-cobicistat 800/150 mg for 7 days. Antiviral therapy associated with low-flow oxygen maintenance led to a rapid clinical benefit. During hospitalization he developed a mild normocytic anemia (Hb 9.9 g/dl, MCV 97.2 fL) which was deemed secondary to chronic inflammation, as shown by high inflammatory indexes (PLT 469,000/mm3, ferritin 1,909 ng/ml, D-dimer 679 ng/ml, CRP 9.51 mg/dl). He was discharged on March 30th. Due to profound asthenia, on April 21st he underwent blood testing that showed worsening anemia (Hb 8.1 g/dl), and on April 28th repeated Sars-CoV-2 nasal swab that tested positive. On May 6th he presented to emergency room for marked fatigue. Severe macrocytic anemia (Hb 5.9g/dl, MCV 125.4 fL), raised reticulocyte count (146.5/1,000 RBC) and lymphopenia (L 960/mm3, ) were found and hemolysis tests showed: total/direct bilirubin 3.16 mg/dl and 0.52 mg/dl, LDH 499 U/L, haptoglobin < 1mg/dl. Direct antiglobulin test was positive (IgG +++). Virological investigations for EBV, CMV, VZV, Parvovirus B-19, and HIV resulted negative. Prednisone 1 mg/kg and transfusion of two packed red blood cells (pRBCs) have restored hemoglobin levels and clinical conditions. Testing for autoimmune or infective underlying causes of AIHA (HBV, HCV, ANA) was negative, and no history of recent drug exposure was reported. We therefore hypothesized that COVID-19 infection might have triggered AIHA.


A 63 years-old woman affected by IgG k monoclonal gammopathy of undetermined significance (MGUS) since 2016, came to our attention in November 2019 for back pain, increased monoclonal component (MC 2.8 g/dl), immune-paresis (IgG 3,828 mg/dl, IgA 30 mg/dl, IgM 31 mg/dl) and unbalanced free light chain (FLC) ratio (free kappa 398.83, free lambda 3.05, ratio k/lambda 130.7). Whole body magnetic resonance (WB-MRI), computed tomography (CT) and positron emission tomography (PET) scan evidenced multiple bone lesions and bone marrow examination detected 15% clonal plasma cells (). Thus, MGUS had progressed to multiple myeloma, international staging system (ISS) stage I. The patient was eligible for autologous stem cell transplantation and started induction therapy with four cycles of bortezomib–thalidomide–dexamethasone (VTD) that induced a partial remission; therefore she was listed for stem cell harvest. On March 18th, 2020 she presented with mild fever and cough; her X-ray chest was normal, but Sars-CoV-2 upper respiratory tract swab resulted positive. hydroxychloroquine (loading 400 mg/bid, then 200 mg/bid/6days), and azithromycin 500 mg/day for 7 days were started and led to complete symptom regression. Nevertheless, on March 31st she was admitted to Hospital for daily fever >39°C, abnormal C reactive protein (CRP 21.22 mg/dl). Serial blood cultures for bacteria and fungi were negative; transthoracic echo cardiac-US was negative for endocarditic vegetation and abdomen CT did not detect any abnormality, whole blood count dramatically worsened showing pancytopenia while inflammation indexes (CRP, IL6, ferritin) were significantly rising (). On April 15th a bone marrow biopsy was performed which revealed a dramatic progression of the MM with 40% of abnormal plasma cells and evidence of hemo-phagocytosis and mild T-cell infiltrate (). Few days later, her general conditions rapidly worsened because of acute respiratory failure, requesting a non-invasive ventilation (NIV). On April 18th a further chest and abdomen CT scan demonstrated segmental pulmonary embolism, ground glass bilateral infiltrates, and multiple subcutaneous lesions. On April 20th she was admitted to intensive care unit (ICU), was intubated, and mechanically ventilated. Bronchoalveolar lavage (BAL) was negative for respiratory viruses, cytomegalovirus, tuberculosis, pneumocystis jirovecii and galactomannan antigen. Skin biopsy detected extramedullary plasma cell infiltrates with evidence of immature phenotype (). Patient’s clinical conditions worsened, multiorgan failure (MOF) ensued which caused her death on May 4th2020.


A 55 years-old woman was diagnosed in 2016 with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) and underwent a combined induction therapy with cyclophosphamide, vincristine, adriamicine, dexamethasone (Hyper-CVAD) and imatinib, followed by a second line with dasatinib in order to reach a deeper response, and finally on June 27, 2016 a 10/10 HLA matched-unrelated donor (MUD) allogeneic stem cell transplantation was performed. Eight months after HSCT she experienced a molecular relapse and acquired the T315I mutation, which was resistant also to ponatinib. Given the high burden of disease, in September 2017 she was enrolled in inotuzumab-ozogamicin compassionate use: up to five-cycle infusions associated with CNS prophylaxis led to a complete, deep and sustained molecular response. Until February 2020 her CSF-immunophenotypic and cytologic analyses remained negative for atypical lymphoid cells, while bone marrow aspirate revealed a BCR-ABL1/ABL transcript of 0.005. On April 8, 2020 she presented to hospital emergency room for mild fever and nausea. Her pharyngeal-nose swab tested positive for Sars-Cov-2, and she started a home treatment with hydroxychloroquine (loading 400 mg/bid, then 200 mg/bid/6days) and darunavir-cobicistat 800/150 mg for 7 days during which her conditions improved. On April 15 her symptoms worsened, and she was admitted to hospital with severe headache and fever. No signs of pulmonary involvement on chest HRCT-scan, and no ischemic or hemorrhagic lesions on brain CT-scan were detected. A lumbar puncture revealed 205 cells/mm3, with 57% lymphoblasts CD19+, CD34+, CD10+, CD20+/−, HLADR+, CD33+, CD117−. Sars-CoV-2 RNA was not found in cerebral-spinal fluid (CSF). Bone marrow aspirate confirmed a molecular relapse of her leukemia by detection BCR-ABL1/ABL transcript of 0.07. Weekly intrathecal chemotherapy with methotrexate 10 mg, cytarabine 40 mg, and dexamethasone 4 mg was started, and strict monitoring of her bone marrow disease has been undertaken to define the type and timing of salvage therapy.


A 93-year old, right-handed man with a history of embolic stroke, hypertension and arterial fibrillation was admitted to the local stroke unit for severe right hemiplegia within 2 hours of symptom onset. He was taking anti-platelet (aspirin 100mg per day) and anti-hypertension medications. He suffered a minor cerebral infarction with sequelae of slight dysarthria 8 years prior. Physical examination on arrival revealed the tight side of limbs with grade 1 as rated by Medical Research Council (MRC) scale for Muscle Strength and severe combined aphasia. A National Institute of Health Stroke Scale (NIHSS) of 23 was scored by the physician. The head computed tomography (CT) at admission revealed no hemorrhage, and slight encephalomalacia in the left parietal and temporal lobe, as well as in the right occipital lobe (.
After excluding contraindications, the patient and his family were informed of intravenous alteplase therapy, including the effects and adverse events. However, alteplase therapy was refused considering the possible adverse events. The patient was immediately transferred to receive digital subtraction angiography (DSA) approximately 2.5 hours from symptom onset. The angiography confirmed a distal occlusion of the M1 segment of left middle cerebral artery and a reduced blood flow in the A4 segment of left anterior cerebral artery (. With a guide wire, an ev3 Rebar 18 micro catheter was first placed gently and cautiously at the proximal end of M1 segment to give an injection of tirofiban (700mg, 62.5g/ml). The subsequent angiography through the micro catheter revealed no obvious change of the blood flow. Then a second dose (700mg, 0.05g/ml) of tirofiban was given through the catheter in the terminal of left internal carotid artery. After 10 minutes, the restoration of blood flow was observed in left middle and anterior cerebral artery (. After the neurointerventional procedure, myodynamia recovered to MRC grade 2 for Muscle Strength in the right lower limb, however, no improvement was found in aphasia. The NIHSS score was then 16. A CT scan the next day indicated no intracranial hemorrhage (. Further diffusion weighted imaging (DWI) showed a new infarction change in left frontal, parietal, temporal and occipital lobes (. One week later, the NIHSS score recovered to 7. After a follow-up of 90 days, the NIHSS score was 7 and the modified ranking score was 2.


We present the case of a 48 years old man, a construction worker, with no significant comorbidities, who suffered a work accident by falling from a building which high estimated about 11 m. Upon arrival to emergency department, the patient was conscious, tachycardic (127 beats per minute), hyperpneic (breathing rate of 25), his blood pressure was 100/60 mmHg, and peripheral saturation of 87% which increased to 93% with supplementary oxygen physical examination found:
Clinical signs of pneumothorax (Asymmetrical lung expansion, Hyper resonant percussion), and graze in his left shoulder and a deformation of his left elbow. A FAST (Focused Assessment with Sonography for Trauma) was done and revealed a left pneumothorax.
The patient was hemodynamically stable so he had a contrast-enhanced computer tomography that showed: a large pneumothorax (more than 30% of the left hemi thorax (around 600 ml of air)), a left lung contusion, an expressive pneumopericardium (about 15mm), and fractures of lines of the left posterior arches of the 1st,10, 11, 12th ribs, fracture lines of the left middle arches of the 3rd,5th,6th ribs, a complex fracture of the left scapula and a simple fracture of the left iliopubic rami (), Splenic contusions, hemoperitoneum in the pouch of Douglas.
The main laboratory findings on admission were normal, as such as: Hemoglobin: 15.2g/dl,
The electrocardiogram showed a tachycardia, The serum troponin I level was 20 times upper normal range. Bone x-ray showed a fracture of the left elbow and the lower extremity of the left radius.
The patient's chest pain resolved within 12 hours of administration of a no steroidal anti-inflammatory agent.
After consultation with the cardiothoracic surgeons, an intercostal chest drain was indicated to relieve the pneumothorax and the pneumopericardium, so a 12-French (F) drain was inserted under local anesthesia and there was an immediate improvement in the patient's pain and all hemodynamic parameters. The drain was swinging and bubbling and he was removed on day 5. We decided not to perform any pericardial drainage procedure (pericardiocentesis or pericardial window) because we were aware that not all pneumopericardium needs draining unless tamponade effect is present.
Follow up chest X-ray showed a reduction in the size of pneumothorax, and A CT scan was performed 24h after, showing a regression of the left pneumothorax and complete relapse of the pneumopericardium (see ).
The Rib fractures were assessed by the orthopedic team, which considered them stable and oriented a conservative management. However, the fracture of the elbow and radius were surgically treated. The iliopubic rami and the scapular fractures were orthopedic.
The patient was discharged home on the 8th day of his admission.


A 66-year-old African American female presented complaining of five days of difficulty swallowing, swelling of the back of her tongue, painful bloody oral white plaques, and cough productive of blood-streaked sputum. Associated symptoms included chills and the onset of right hand swelling and pain of the right knee.
Her past medical history included rheumatoid arthritis, obesity, type 2 diabetes mellitus, crystal-proven gout, vitamin D deficiency, stage III chronic kidney disease, macrocytic anemia, hypertension, and two episodes of tonsillitis treated with antibiotics in the last two years. She had been diagnosed with RA (ANA+, RF+, CCP-) two years earlier and treated with renally dosed MTX (10 mg) weekly and daily folic acid supplementation with a 1 mg dose. Sulfasalazine 500 mg every 12 h had been added four months prior to presentation to improve disease control. The patient reported taking her last dose of MTX two weeks prior to presentation—she had been advised by a pharmacist to hold MTX when she began a course of amoxicillin clavulanate for a toenail infection. Other medications included metformin, glipizide, hydrochlorothiazide, carvedilol, amlodipine, clonidine, hydralazine, allopurinol, and vitamin D. She denied smoking, alcohol use, or use of recreational drugs.
On physical exam she had a temperature of 38 °C (100.4 °F), a heart rate of 124 beats per minute, and relative hypotension with a blood pressure of 101/77 mmHg. Physical exam revealed dry mucous membranes, severe mucositis, oral candidiasis, active synovitis of the right wrist, and right knee tenderness. She was awake, fully oriented, and had no neurological symptoms.
Laboratory work-up showed pancytopenia, macrocytosis, acute kidney injury, a high serum folate level of 20 ng/ml and a vitamin B12 level of 127 pg/mL (Table ). Right knee arthrocentesis revealed urate crystals. On admission, medication toxicity was suspected, and methotrexate, allopurinol, sulfasalazine, and metformin were held, while folic acid and vitamin D were continued. She was treated with fluids and broad-spectrum antibiotics for tonsillitis due to febrile neutropenia. Prednisone treatment for a gout flare was initiated. During this hospitalization she was additionally diagnosed with pernicious anemia (positive intrinsic factor antibody and negative parietal cell antibody) and received vitamin B12 injections (1000 μg daily for a week) for repletion.
Throughout the patient’s hospital course, no fevers recurred. Blood and synovial fluid cultures were sterile. No focus of infection was identified other than oral candidiasis, which was treated with fluconazole for 7 days. Broad spectrum antibiotics were discontinued. By day 4, mucositis began to improve to the point that the patient could tolerate a liquid diet. Pancytopenia persisted, however, with a platelet nadir of 49,000/uL, and leucovorin (10 mg every 6 h) was added to her regimen on day 6. By day 7, significant improvement in mucositis had occurred, pancytopenia was resolving, and she was discharged home with leucovorin, weekly B12 injections, prednisone, insulin and antihypertensives. Four days post-discharge, the WBC count was 13,900 cells/uL, the platelet count was 688, 000/uL (Table ), and the patient had resolution of all her symptoms. Subsequently, prednisone was discontinued and etanercept was started after a negative purified protein derivative (PPD) skin test. No complications occurred during ten months of follow-up. The macrocytosis persisted with an MCV of 105, likely due to inadequate vitamin B12 replacement, as a recent vitamin B12 level was only 248 pg/ml. In follow-up, the patient reported satisfaction with her new treatment and denied adverse effects.


An 81-year-old Asian man who was hit by a car while riding on a bike was transferred to our emergency room. He had no neurological symptoms except numbness in the right C6 dermatome area. Computed tomography (CT) of his cervical spine showed a right minimally displaced facet fracture of C6. The fracture fragment size was 6 mm, involving 25% of the height of the intact lateral mass (Fig. ). CT angiography (CTA) at initial survey revealed a right blunt VAI, which was overlooked at initial admission (Fig. ). CTA was used because it is integrated into a whole-body CT protocol for patients with high energy or multiple traumas. His blood data showed no abnormal findings of coagulation or platelet count. The fracture fragment was small, and the fracture was considered stable and the patient was treated with a Philadelphia collar and discharged four days after admission. We ordered magnetic resonance imaging (MRI); however, the patient could not undergo MRI during his first hospital stay. In addition to the MRI reservation being full, an MRI was deemed less urgent as he had no motor deficit. A visit to the outpatient department, including an MRI, was scheduled nine days after injury. However, 9 days after the injury, he developed quadriplegia gradually and was re-admitted to the hospital. He presented with complete paralysis of the lower extremity and bilateral motor weakness of the upper extremity including the elbow flexors and extensors, wrist extensors, and the finger abductors and flexors. Muscular power was graded as 0/5 to 4/5 by manual muscle testing (MMT). His neurological level of injury (NLI) was C4, and American Spinal Injury Association (ASIA) Impairment Scale was A. MRI at re-admission showed a disc injury at C5/6 with spinal cord compression from a posterior epidural mass accompanied by intramedullary signal intensity changes at the same level (Fig. ). Immediately after admission we surgically performed a mid-splitting laminoplasty with instrumented fusion of C5–6 using lateral mass screws (Fig. ). At surgery, fibrous scar tissue compressing the posterior aspect of the cord was observed and removed. We consulted a neurosurgeon about the blunt VAI, and the patient underwent endovascular stenting. At four months after surgery motor function in his upper extremities had improved and he was able to eat by himself using an assistive device but motor loss persisted in both of his legs.


A 74-year-old Asian female who fell off a chair and hit her head was transferred to our emergency room. Upon arrival at our hospital, she had motor weakness of the left elbow flexors and extensors, wrist extensors, and both finger abductors. Muscular power was graded as 3/5 to 4/5 by MMT. There was no lower extremity weakness, indicating that she had central cord syndrome. Computed tomography of her cervical spine showed signs of instability, including a widening of the right C4/5 facet joint space, left facet fracture of C4/5 and anterior subluxation of C4 (Fig. ). The fracture fragment size was 6 mm and involved 25% of the height of the intact lateral mass. An MRI showed an intramedullary signal change of the spinal cord with disc injury at the C4/5 level (Fig. ). Preoperative CT angiography revealed a left blunt VAI (Fig. ). We consulted a neurosurgeon, and the patient underwent endovascular stenting. After endovascular therapy, we performed combined anterior-posterior fusion surgery with a cage and lateral mass screws bilaterally at the C4–5 level (Fig. ). For this case we used a combined anterior-posterior approach to avoid disc collapse and kyphosis. Generally, an anterior or posterior only approach yields favorable outcomes for this type of injury [–]. The patient presented numbness of her left arm but no motor weakness two years after surgery.


An Iranian 50-year-old man attended Taleghani Gastrointestinal Clinic for recurring epigastric pain. This patients complaints included epigastric pain, heartburn and dysphagia. He suffered from these signs and symptoms from four months before the tumor detection. No weight loss was detected. Past surgical history and family history of the patient were negative too. He did not smoke or drink alcohol. He was treated several times with omeprazole, anti-acids, and baclofen. Finally, he was referred to Taleghani Hospital Clinic by food sensation. In our setting, he was evaluated by endoscopy and a submucosal mass in cardia was detected.
On physical examination, his temperature was 37.1°C, heart rate was 82 beats per minute, respiratory rate was 10 breaths per minute, and blood pressure was 130/80 mm-Hg. Abdominal examination showed neither distention nor tenderness. No organomegaly or palpable mass was found. Furthermore, laboratory tests had no remarkable findings. The evaluations included endoscopy of upper and lower gastrointestinal tract at the same time. The result of colonoscopy was normal. Endoscopy of the upper GI tract showed a 19×13 mm homogenous and hypoechoic submucosal lesion, with smooth and defined border in cardia at the third layer. In addition, EUS reported a small calcification in the center of lesion.
An Iranian 40-year-old lady was referred to the gastroenterology department of Taleghani Hospital with a submucosal mass lesion. The patient described her symptoms as intermittent epigastric pain, discomfort, dyspepsia, and heartburn from more than six months before the admission. No significant weight loss was detected in our case. She revealed two caesarean sections as the past medical history and the family history of gastrointestinal malignant disorders was negative. In addition, she denied any positive history of alcohol drinking or smoking.
On physical examination, her temperature was 37.6°C, heart rate was about 84 beat per minute, and blood pressure was 110/70 mm-Hg. Abdominal examination showed a soft and non-tender abdomen with no sign of organomegally or palpable mass. The rest of the physical examinations and laboratory tests were normal.
The evaluations before the referral included upper and lower GI tract endoscopy and ultrasonography. Endoscopy reported a polyp-like lesion in the antrum, while the mucosa in this place was normal. In addition, EUS showed a 16.3 mm subepithelial, iso-hyperechoic lesion originating from the submucosal layer. The pillow sign of the mass was negative. The gross feature of the lesion was in favor of lipoma.
A soft, straight, transport cap with an inside rim (D-201-11802, Olympus) was fitted on to the tip of a standard single channel endoscope (GIF-260, Olympus). Other devices included Needle Knife (Olympus), Hot snares, and Hemoclips (Micro-Tech Nanjing Co., Ltd.).
Under sedation with intravenous propofol in standard position, endoscopy was performed. The procedures included the following steps and all of them were attended by an expert and single endoscopist ().
The submucosal lesion was detected by retroflexed maneuver. Then, after the estimation the site of the polyps. The mucosal surface was unroofed with needle knife (this part is different with other previous known methods.). The lesion was retracted with grasps, and the mass was enucleated. It was resected with standard polypectomy hot snares. After resection, the mass was sent to a pathologist. Two hemoclips for each mass were inserted on the base of the lesion ().
In both cases, second look endoscopy was performed after six hours of the resection. The outcomes were followed up by endoscopy after the two months following the procedure, to confirm the healing of the artificial ulcers and other complications. The assessment of endoscopic parameters included resection rate, early and delayed perforation rate, early and delayed bleeding rate, dehiscence rate, and recurrence rate.
In both cases, the tissue specimens were fixed in formalin solution. The histological analysis included the identification of cell types, nuclear atypia, histopathological type, tumor size, and tumor invasion. In the first case, immunohistochemical study was also performed. Furthermore, the margins of resection were examined macroscopically and microscopically.
The specimen consisted of a polypoid creamy tissue fragment measuring 1.7×1.5×1 cm and tiny fragments of creamy soft tissue measuring 1×0.7×0.3 cm. \4The primary histopathological analysis suggested gastrointestinal stromal tumor (GIST). IHC study included Smooth Muscle Antibody (SMA), Desmin, CD117, and DOG1. Desmin and SMA were positive but CD117 and DOG1 were negative. IHC and histologic findings were in in line with leiomyoma.
The specimen consisted of adipose tissue fragment measuring 1×1×0.5 cm. Histologic findings of endoscopic biopsy confirmed lipoma.
Re-endoscopy, after six hours of resection reported no early complication, in both cases. After 12 hours of the procedures, both patients were discharged. Once discharged, the patients were prescribed daily oral Proton pump inhibitors (PPI) for two months. After two months, patients were evaluated by endoscopy again. Repeated endoscopy revealed, the hemoclips were spontaneously removed and the mucosa of the antrum was normal, in both cases. No macroscopic evidence of tumor was detected. Furthermore, the resection margins of the polyp were evaluated microscopically. Microscopically, all margins were free. Delayed perforation or delayed bleeding were not detected after 2 months.


A 67 years old white woman related severe headaches, dating from one month ago. She had no other symptoms and no family history of migraines or glaucoma as well. A pars plana vitrectomy in OD with SiO tamponade (5000 cSt) was performed in 2016 due to a tractional-rhegmatogenous retinal detachment caused by proliferative diabetic retinopathy. The patient evolved with intraocular hypertension and glaucoma in the same eye, being later submitted to a trabeculectomy (2018) and to a cyclophotocoagulation in 2019.
The patient had a vision of no-light perception in OD and 20/50 in OS (+ 3.00 −1.75 × 90). On the slit-lamp biomicroscopy examination of OD, the patient was pseudophakic with a significant posterior capsule opacification, while the left eye was unremarkable. The intraocular pressure was 20\16 mmhg by Goldmann’s applanation tonometry. The posterior segment examination showed the presence of SiO and a total excavation of the optic disc with intense optic disk pallor in OD. There was an inferior retinectomy associated with subretinal PVR next to inferior vascular arcades. In the left eye, there was a physiological optic disc cupping and a PDR.
Magnetic resonance imaging (MRI) was performed, demonstrating an ovoid lesion within the frontal horn of the right lateral ventricle. The T2 weighted images showed migrated SiO in the horn of the lateral ventricle, and it can be seen in Figs. and a. Figure b shows a T1 weighted MRI Sagittal Cut image with a hyperintense ovoid lesion on the frontal horn of the lateral ventricles as well. The patient was evaluated by the neurosurgery department, in which they opted for clinical observation, oral analgesia with metamizole, and close follow-up. According to the patient, the headaches episodes diminished considerably, both in frequency and intensity. We performed panretinal photocoagulation in the left eye due to PDR, and the patient maintained a stable neuro-clinical condition until the submission of this article.


A 49-year-old male with a past medical history of hypertension, hyperlipidemia, posttraumatic stress disorder, and depression presented to the emergency department with complaints of diffuse abdominal pain, diarrhea, weight loss, night sweats, and subjective fever.
One month prior to admission, the patient suddenly developed diffuse, sharp abdominal pain, which was associated with nonbloody diarrhea, nausea, and night sweats; it was aggravated by eating. History was notable for a 40 lb unintentional weight loss prior to the onset of symptoms. The patient's surgical history was insignificant. Family history was notable for lymphoma in a first-degree relative and an uncle who died from colon cancer at the age of 62.
On examination, vital signs were unremarkable. Physical examination revealed diffuse abdominal tenderness without rebound tenderness or guarding. Rectal exam was normal, and the stool occult was negative for blood. Laboratory studies were notable for leukocytosis 12.2 × 103/mcL with left-sided shift, erythrocyte sedimentation rate 20 mm/hr, and mild transaminitis; electrolytes, creatinine, lipase, C-reactive protein, lactic acid, lithium levels, ANA, and rheumatoid factor were all within normal limits. Stool examination revealed no ova or parasites, and C. diff toxin and culture were also negative.
CT scan of abdomen and pelvis with contrast was done demonstrating hazy infiltration with subcentimeter lymph nodes, slightly more prominent in the right abdomen, which was concerning for sclerosing mesenteritis and mild splenomegaly (). The hospital course was complicated by severe pain and vomiting requiring intravenous opiates. Diagnostic laparoscopy was pursued which revealed mosaic white stranding of the proximal mesentery in the areas involved (). Biopsy of small bowel mesentery showed mature adipose tissue with patchy chronic inflammation and fat necrosis; thus, the diagnosis of SM was established (). The patient was initially treated with tamoxifen 10 mg BID and prednisone 40 mg with no improvement within 3 months of therapy. This patient was not able to tolerate an oral diet, suffering abdominal pain and watery diarrhea after each meal. Overall, he had 60 lbs of weight loss. In the next phase of treatment following steroid/tamoxifen resistance, the patient was started on total parenteral nutrition (TPN), adalimumab 80 mg subcutaneously every 14 days and pentoxifylline 400 mg PO TID, while steroids were tapered off in an appropriate manner. Four months after treating the patient with adalimumab/pentoxifylline therapy, he started feeling better, and he was taken off TPN, able to tolerate 1 meal/day, and maintained weight.
Meanwhile, the patient was still experiencing night sweats periodically. Since SM is associated with various malignancies, including GI adenocarcinoma, the patient underwent an extensive workup. Esophagoduodenoscopy/colonoscopy was done and did not reveal any significant abnormality. PET scan was also performed and did not demonstrate any lymphadenopathy or abnormal FDG activity within the mesentery. Liver, gallbladder, adrenal glands, spleen, and pancreas had normal appearance as well.


A 57-year-old woman with IV stage pulmonary adenocarcinoma (G3 pT1b pN0 M + , PD-L1 40%, EGFR/ALK WT, ROS1-) was admitted to the Emergency Department (ED) of our Hospital and then hospitalized to the Department of Internal Medicine for diarrhea (up to 15 episodes of watery stools per day), asthenia, fatigue, loss of appetite, without fever, or other associated symptoms.
Past medical history dates back to 2015 when the patient underwent medial lobe lobectomy plus hilar lymphadenectomy for tumor resection. In 2016, a left parieto-occipital craniotomy was performed for resection of an occipital cerebral metastasis, followed by radio-chemotherapy with carboplatinum and paclitaxel. In December 2018, she started atezolizumab therapy due to primary neoplasia relapse. Two weeks later, the patient presented not bloody diarrhea (no more than five episodes of watery stools/day). She did not experience any fever, chills, vomiting, abdominal pain, and cramps. Loperamide, probiotics, and rifaximin were administered without any benefit. Since worsening of diarrhea, up to 15 watery stools per day, she was hospitalized in February 2019. Due to suspicion of severe immune-related gastro-intestinal toxicity, atezolizumab was discontinued. At that time, the patient was not on chronic therapy, in particular not with proton pump inhibitor (PPIs), histamine type 2 receptor antagonists (H2 blockers) neither with non-steroidal antiinflammatory drugs (NSAIDs) or serotoninergic agents, all of them usually being considered as potential triggers of development of microscopic colitis in susceptible individuals []. On physical examination, the patient appeared fatigued, but vital signs were normal. Blood chemistry showed no remarkable findings, except only for a slight increase of serum creatinine and low levels of serum potassium. Stool exams were negative for bacterial and parasite infection. Candida was found and treated with oral nystatin without clinical benefit; therefore, an infective cause of diarrhea was recognized as less probable. Gastroscopy and colonoscopy (Fig. ) did not show significant macroscopic findings. However, since the high clinical suspicion of colitis, endoscopist made random colon biopsies after consult with Oncologist and Clinical Physicians. Microscopic examination of colonic mucosa showed expansion of lamina propria by lymphoplasmacytic infiltrate, intraepithelial neutrophils, crypt abscesses, and a thickened subepithelial collagen layer enhanced, thus resembling a form of collagenous colitis mixed to elements typical of acute neutrophilic inflammation (Fig. a–b). Methylprednisolone (1 mg/kg/day) treatment was started, and few days later, diarrhea decreased significantly (up to two episodes per day).
Steroid therapy was slowly tapered within 6 months, but the attempt to completely discontinue the treatment led to reappearance of intestinal symptoms. After 1 year, patient is well on methylprednisolone 4 mg/day and neoplastic picture is unchanged, despite discontinuation of oncologic therapy. However, at follow-up colonoscopy, histological examination still shows a collagenous colitis picture, though without signs of acute neutrophilic inflammation (Fig. c).
Clinical course of disease in our patient was summarized in a timeline (Fig. ).


A 23-year-old woman visited a local medical doctor with abdominal distension and anorexia. Computed tomography (CT) showed ascites, a huge hepatic tumor, and an ovarian tumor (Fig. a, b). Therefore, she was referred to our hospital. The patient had no history of previous illness and no family history of hereditary diseases. She had no habits of smoking and drinking. On physical examination, she looked pale, her palpebral conjunctivae were anemic, and her abdomen was distended. She had anemia with a hemoglobin level of 4.3 g/dl on blood examination, but the levels of tumor markers, CEA, and CA19-9 were normal. CT showed marked gastric mucosal hypertrophy, a large amount of ascites, a huge hepatic tumor and an ovarian tumor. Gastroscopy revealed poor distension of the gastric wall with a large, irregular-shaped ulcer in the gastric body (Fig. a), and she was diagnosed with type 4 gastric cancer. Upper gastrointestinal series showed narrowing of the gastric lumen, but contrast agent could pass through the strictured segment (Fig. b). Pathological examination of a biopsy specimen revealed poorly differentiated adenocarcinoma with signet ring cell carcinoma (HER2-negative). The final diagnosis was advanced gastric adenocarcinoma, clinical stage IV. She received chemotherapy with a combination regimen of S-1 and CDDP. She developed acute kidney injury; therefore, this regimen was changed to two courses of the SOX (S-1 + OHP) regimen. After she received one course of the SOX regimen, she developed general muscle cramp. Gastroscopy revealed that the mucosal findings were improved and CT showed that the hepatic tumor was reduced in size (Fig. a, b). Seventy-eight days after the start of chemotherapy, she was transported to our hospital by ambulance for convulsion. Magnetic resonance imaging (MRI) showed a 15 mm, round signal at the parietal lobe in T2-weighted images (Fig. a). She was hospitalized due to suspicion of brain metastasis. Anticonvulsants improved her general muscle cramp, but she had consciousness disturbance on the 9th hospital day. Hypertension (BP: 155/114 mmHg) and hyponatremia (Na: 128 mEq/L in the blood test) were also found. T2-weighted images showed high-intensity signals within the cerebral white matter at both sides of the occipital lobe (Fig. b). We suspected leukoencephalopathy caused by S-1; therefore, we discontinued the SOX regimen. Furthermore, we administered an antihypertensive agent and electrolyte replenisher for the treatment of hypertension and hyponatremia. Her consciousness disturbance improved in a few days, and follow-up MRI (T2WI) findings were markedly improved on the 20th hospital day (Fig. c). We diagnosed the patient as having PRES caused by chemotherapy containing S-1.


A 48-year-old Caucasian male with no prior personal or family history of mental health diagnosis presented with new-onset psychosis, status post-ischemic stroke after motor vehicle accident (MVA). He suffered from an MVA in which he was an unrestrained passenger sustaining a head-on collision without loss of consciousness. He was heavily intoxicated by alcohol. Workup during hospitalization identified a fracture of the right femur in radiological reports. He had open treatment of femoral supracondylar fracture with intercondylar extension. The patient’s urine screened positive for tetrahydrocannabinol (THC), and opioids prescribed were prescribed to the patient.
The patient suffered from a stroke one week after the MVA. The stroke resulted in right-sided limb weakness, dysarthria, and right facial droop. Psychosis started a few days after the stroke. Symptoms included auditory hallucinations (AH), persecutory delusions about being watched through cameras, thought broadcasting through microphones, having ideas of reference about receiving special messages through television. In 2017, he set his house on fire and injured his father secondary to commanding AH, leading to legal charges against him. He frequently felt aggravated as a result of the commanding AH and at times, also acted on those commands. He described feeling depressed when not angry or irritable. He has not been employed since the MVA. Sleep, memory, and ability to concentrate are poor due to ongoing AH. His medical history includes stroke in 2016, asthma, heart implant, intramedullary rods in both legs, limping gait, arthritic changes in the right knee, and right elbow injury. History of substance use was clinically significant for methamphetamine abuse that started two months after the MVA. He remained sober from alcohol for over a year at the time of the report, however used tobacco dips regularly. Family history was significant for stroke in his paternal lineage (father and grandfather); and no known family history of mental health diagnosis.
The patient was initiated on the trial of olanzapine and divalproex and doses were titrated slowly to olanzapine 20mg every night (qHS) and divalproex 500mg twice daily (BID). These medications did not resolve the symptoms of psychosis substantially. The positive and negative syndrome scale (PANSS) score before initiation medicines was 180, and after adequate dose trial decreased to 147. Therefore, combinatorial pharmacogenomics testing was performed to guide the treatment of choice for psychotropic medication regimen. Test results did not indicate any gene interaction with the majority of antipsychotics. Among selective serotonin reuptake inhibitor (SSRI), fluoxetine and paroxetine were predicted to have moderate and severe interactions, respectively. However, other antidepressants showed no significant interactions. The human serotonin transporter gene (SLC6A4) showed a normal response, and the patient was noted to be homozygous for long promoter polymorphism of serotonin transporter. Serotonin receptor 2A (HTR2A) homozygous variant for allele concluded an increased risk of adverse reaction with SSRI. Human leukocyte antigen (HLA)-b*1502 and HLA-a*3101 has low risk, as they do not carry this allele.


A 6-year-old Chinese girl is presented to our clinic complaining about night blindness and progressive decreased vision in both eyes for one month. There was no consanguineous marriage and family history of ocular disorders. Best corrected visual acuity (BCVA) was 20/63 in the right eye and 20/100 in the left eye with a refraction error of -7.50 diopter (D)/-2.50D×175° and − 5.00D/-2.75D×180°, respectively. Slit-lamp examination of the anterior segment was unremarkable in both eyes. Dilated Fundus examination showed bilateral multiple, sharply demarcated, scallop-shaped chorioretinal atrophy areas in the midperipheral and peripheral of the fundus (Fig. a, b). Fundus autofluorescence showed hypo-autofluorescence in the corresponding area of chorioretinal atrophy (Fig. c, d).
Spectral domain optical coherence tomography (SD-OCT) showed increased central macular thickness (CMT) in both eyes (CMT of 645 µm and 648 µm in the right and left eye, respectively), with multiple intraretinal cystic spaces (Fig. a, b). There was no leakage or staining in macular area on the late phase of fluorescein angiography (FA) (Fig. e, f).
The plasma ornithine level was 1180µmol/L (normal range: 25–115µmol/L), which supported the diagnosis of GA. Whole-exome sequencing in family trios by the Beijing Genomics Institute (Beijing, China) identified two novel mutations in the OAT: (NM_000274.3): c.251 C > T p. (Ser84Phe) and c.648 + 2T > G. Heterozygosity of OAT: c.251 C > T p. (Ser84Phe) was confirmed in the patient’s father and OAT: c.648 + 2T > G was found in the patient’s mother. Vitamin B6 supplementation (dosage of 500 mg/day) was prescribed but low-protein diet is difficult for a 6-year-old patient. The vitamin B6 was reduced to 300 mg/d in the third week due to muscle pain in arms and legs, which was considered as the side effects of vitamin B6. Three weeks after treatment, serum ornithine levels did not decline, despite the patient’s reporting strict adherence to the vitamin B6 supplementation. SD-OCT scans showed reduction of CMT with partial regression of intraretinal cystic spaces (CMT of 554 µm and 572 µm in the right and left eyes, respectively) (Fig. c, d). However, the patient discontinued therapy due to severe muscle pain, and CMT increased to its original level a month later. The BCVA in both eyes remained stable during the next five months.


A 90-year-old female was referred for dyspnoea on exertion. On auscultation, mid-systolic grade III murmur was heard at the left sternal border. Electrocardiogram showed sinus rhythm, and her left ventricular ejection fraction was preserved (66%). Transthoracic echocardiography showed severe aortic stenosis with a peak trans-valvular jet velocity of 4.1 m/s, a mean pressure gradient of 42 mmHg, and an aortic valve area of 0.75 cm2. The degree of aortic regurgitation was trivial, with no other structural heart abnormality. She had a history of hypertension and hypothyroidism. The patient had been taking administered azosemide 7.5 mg, amlodipine 5 mg, candesartan 8 mg, and cilnidipine 5 mg. She was mildly frail with frailty index of 5 and Katz index was 5 out of 6. N-terminal prohormone of brain natriuretic peptide was 212 pg/mL (normal value <450 pg/mL for patients aged 75–99 years). Estimated mortality risk for isolated surgical aortic valve replacement was 5.28% according to the Society of Thoracic Surgery risk score. Considering her age, frailty, and the intermediate risk for surgical aortic valve replacement, trans-femoral TAVI for symptomatic severe aortic stenosis was planned by the heart team. Coronary angiography showed severe stenosis in the proximal right coronary artery that was fixed by drug-eluting stent implantation before TAVI in staged approach and no significant stenosis in left coronary artery.
Before the procedure, computed tomography (CT) scan showed a 5 mm width calcified plaque protruding into the lumen of the abdominal aorta (). Since the lumen measured 10.0 mm, and the 14 Fr expandable sheath was 6.0 mm, we determined that the 14 Fr expandable sheath could pass through the abdominal aorta. The basal annulus area was 343 mm2, and the perimeter was 66.3 mm. Trans-femoral-TAVI was planned with an access from the left femoral artery with a 23 mm balloon-expandable valve.
Because the ostium of the left coronary artery was low, at 8 mm above the annulus, a guidewire was placed in the beginning of the procedure to prevent coronary obstruction. The height of right coronary artery origin was sufficient at 11 mm. To confirm that the transcatheter heart valve (THV) was not occluding the left coronary artery during the procedure, general anaesthesia was given to enable the real-time observation with TOE. A temporary pacemaker was placed in the right ventricle through right jugular vein.
During the procedure, the 14 Fr expandable sheath did not initially pass the abdominal aorta. The extra-stiff wire was exchanged for a Lunderquist extra-stiff wire, and another Lunderquist extra-stiff wire was added from the right femoral artery as a buddy wire, but the sheath could not still ascend farther than the terminal aorta. Balloon angioplasty was carefully performed at the abdominal aorta with a 12 mm balloon at 4 atm, which finally enabled the sheath to ascend past the calcified plaque. Heparin was given and activated clotting time (ACT) was 307 s.
A 5 Fr Amplatz left 1 catheter and a straight wire were used to cross the aortic valve, and then exchanged to a 5 Fr pigtail catheter and an angled hydrophilic wire. Finally, the wire was exchanged with a Safari extra small wire in the left ventricle. After ACT was reconfirmed at 298 s, the balloon aortic valvuloplasty was applied with a 20 mm balloon. Afterwards, the delivering system was advanced. Just before the implantation of the THV, TOE showed the sudden appearance of a high echoic, 10 mm long mass attached to the THV (). We discussed whether the mass could possibly embolize, but the cerebral embolic protection (CEP) device was not available in Japan. Moreover, the delivering system had already advanced past the native aortic valve, and as retraction of the device would cause the mass to detach from the THV, we decided to proceed with the implantation. After the implantation of the THV under rapid right ventricular pacing, the mass gradually enlarged to 26 mm, which then spontaneously detached from the THV and flowed up the ascending aorta, disappearing from the TOE field of view (Figure and Video 1). The stroke team immediately performed cerebral angiography, but no major cerebral trunk was occluded.
After the procedure, the patient presented with hemianopsia and ataxia. Acute cerebral infarction was found in magnetic resonance imaging that was not observed pre-procedurally (). The patient’s stroke was thought to have resulted from the embolism migrating to the distal cerebral arteries. There were no signs of systemic embolization in CT.


A 57-year-old female patient presented with the diagnosis of cT3N1 right breast invasive ductal carcinoma. No distant metastatic disease was noted on staging imaging. After completing neoadjuvant chemotherapy, the patient underwent a right skin-sparing mastectomy, sentinel lymph node biopsy and targeted axillary lymph node dissection, and immediate stage I breast reconstruction with tissue expander placement. Intraoperatively, 1 of 3 axillary lymph nodes was positive for malignancy on frozen section and a level I and II right axillary lymph node dissection was completed. Multiple bulky and soft nodes were found in the axilla. The wound was irrigated, and no bleeding or lymphatic leakage was noted. The remainder of the operation was completed without complications. One drain was placed in the right axillary dissection region, and two additional drains were placed at the right breast following the tissue expander placement.
On the first postoperative day, all three drains were found to have serosanguinous drainage at 12 hours postoperatively. At approximately 18 hours postoperatively, the patient was noted to have 100 CC of milky fluid in the right axillary drain. The differential diagnosis for the milky drainage included lymphatic obstruction due to the bulky lymph nodes found at the time of dissection and a right-sided chyle leak. Triglyceride level was sent on the drainage and returned elevated at 1,425 mg/dl. Drain fluid triglyceride levels > 100 mg/dl confirm the diagnosis of chyle leak []. The patient was managed in a conservative fashion with pressure dressings to the right axilla. She was instructed to follow a low-fat diet and discharged home on postoperative day 2.
The patient followed up in clinic on postoperative day 12. She reported that axillary drain fluid turned serous and decreased in output, approximately 50 cc/day. It was recommended that the patient continue conservative management with the drain in place and pressure dressing. One week later, the patient reported 27 cc of serous drainage in the past 24 hours. The patient was recommended to discontinue the pressure dressing at this time. The patient presented two days later with scant serous discharge in her drain. The drain was removed on postoperative day 20.


An 11-year-old male presented with a painless mass over the superior aspect of the globe for the last three months which was progressively increasing in size. The child had progressive, painless loss of vision in the same eye for the last three years. On ocular examination, visual acuity was no perception of light in the same eye and 6/6 in the other. Firm, non-tender mass measuring 4cm x 3cm was noted in the superior aspect of the globe (). It was covered by conjunctiva in the posterior half, while conjunctiva was adherent on the anterior half. Its surface was irregular with some vascularization. The cornea was hazy due to scarring, and inner details could not be evaluated. The examination of the left eye was within the normal limit. Systemic examination was normal with no palpable lymph nodes. B-scan ultrasound showed homogenous opacity in the anterior part of the eye with moderate reflectivity persisting up to 70dB. CT-Scan of the orbit revealed hyperdense focus attached to the anterior surface of the eyeball with surrounding thickening, likely foreign body with an irregular wall of the globe with areas of internal hyperdensity likely a hemorrhage or infection ().
After consent, enucleation was performed with minimal manipulation under general anesthesia with the orbital implant and conformer. The specimen was sent for histopathological examination.
Gross examination of a cross-section of the enucleated globe revealed a solid grey lesion with exophytic and endophytic components (Figure 2.a and b). Histopathological examination revealed thick bands of polarized epithelium resembling medullary epithelium along with thinner cellular strands of acellular myxoid stroma (Figure 3.a). The tumor cells aggregated radially along the central space forming Flexner Wintersteiner rosette (Figure 3.b). It also involved the anterior chamber and vitreous cavity, but the optic nerve stump was free of tumor. This was highly suggestive of medulloepithelioma grade II. The origin of medulloepithelioma could not be confirmed.
The child is under regular follow-up. He is healthy, and there is no recurrence seen at one year of follow-up.


A 64-year-old female was brought into the emergency department following an episode of loss of consciousness, which was associated with hypoglycemic symptoms of sweating, shivering and dizziness. The random blood sugar level on presentation to the emergency room was 40 mg/dL (2.2 mmol/L). She was given intravenous dextrose infusion to regain consciousness.
She has diabetes for 15 years. She had been on insulin and oral diabetes medications. Her heamoglobin A1c (HbA1c) was 11.7% (104 mmol/mol) three months prior to presentation to the emergency room. However, her HbA1c was reduced to 6.5% (38 mmol/mol) upon her admission with hypoglycemia. Her blood glucose levels remained low despite discontinuation of diabetic treatment. Frequent 10% dextrose infusions were required. Nonetheless and even with close monitoring, she further developed hypoglycemic episodes requiring ICU admission. While in ICU, she developed generalized tonic-clonic seizures. Following this, a brain MRI was done, which revealed nothing significant except a partially empty sella turcica (Figure ).
Her initial hormone workup revealed low cortisol, low follicular stimulating hormone (FSH), low luteinizing hormone (LH), low somatomedin level and low ACTH levels with normal thyroid-stimulating hormone (TSH), normal aldosterone, normal renin, normal aldosterone/renin ratio and normal prolactin. She had low morning cortisol of 25 nmol/L and low ACTH of 0.44 pmol/L. Further assessment showed poor response to short Synthacten test with cortisol levels of 24.7, 95.8 and 130.5 nmol/L at 0, 30 and 60 minutes, respectively (summarized in Table ).
The patient was diagnosed with primary pituitary failure with secondary adrenal insufficiency considering the investigation results. She was started on IV hydrocortisone followed by oral hydrocortisone 10 mg twice daily and was discharged on the same dose of hydrocortisone, in addition to oral hypoglycemic medications (linagliptin, empagliflozin and metformin). Since then, no more episodes of hypoglycemia have been reported and she remained stable over the remaining course of her hospital stay. Upon her follow-up visits in the outpatient clinic for the last five months, she reported improvement in her symptoms with no further hypoglycemic episodes with well-controlled self-home blood glucose monitoring.


A 26-year-old male, who is medically and surgically healthy, presented with a six-month history of right-sided throbbing headache associated with nausea, vomiting, and photophobia nearly every day. The headache is preceded by 15-30 minutes of blurry vision. Initially, the pain was relieved by lying down in a dark, quiet room or oral acetaminophen. Later, the patient required ibuprofen to alleviate the pain as the headache would persist for two days. Initial examination showed a blood pressure of 123/69 mmHg, a heart rate of 72 beats per minute, and a normal respiratory rate. The neurological examination was completely unremarkable. The basic blood tests were within normal limits.
The patient was diagnosed with migraine headache and started on flunarizine 10 mg once daily. A month later, the patient did not feel any improvement; thus, he has switched to amitriptyline 10 mg once daily. After a month, the dose was increased to 25 mg as there was no improvement. The patient migraine attacks improved to once monthly; however, the patient noticed a new headache character affecting the head's posterior part, not similar to his previous migraine three months after starting amitriptyline. The examination was normal, apart from a blood pressure of 161/82 mmHg. He was asked to monitor his blood pressure at home, which showed an average reading of 160/80 mmHg with few readings reaching 180/90 mmHg. He denied any history of other medications or illicit drug use.
The patient decided to stop amitriptyline and monitor his blood pressure, which normalized after one week. On the next clinic visit, his blood pressure was 111/62 mmHg, and the migraine headache was persistent but responding to analgesics. He was asked to resume amitriptyline to 10 mg and monitor blood pressure, then increase the dose to 25 mg if migraine was not controlled and blood pressure did not increase. After one month, the patient's blood pressure was normal, but he still complains of migraines, so he increased the dose to 25 mg as instructed. However, a week later, the patient's blood pressure readings were high, so the patient stopped amitriptyline. Table shows the patient's blood pressure readings. After six months, the patient was not on any medications, and his blood pressure remained normal. His migraine attacks were much less frequent and responding to simple analgesics.


A 55-year-old male patient (body height 160 cm, body weight 58 kg, body surface area 1.6 m2 and standard liver volume 1132.3 ml) was admitted to our department on April 08, 2018, due to a focal liver lesion found on physical examination 1 month prior. Approval to perform ALPPS was obtained, as well as patient consent ().
Laboratory examination: alpha fetoprotein 3403.00 μg/l, Child-Pugh A level (total bilirubin 8.1 μmol/l, serum albumin 41.2 g/l, international standardized ratio 1.15, no ascites and hepatic encephalopathy) on April 7, 2018.
Imaging examination: The patient underwent MRI examination in our hospital on April 4, 2018. The results showed two lesions in the liver. One of 59 × 53 mm was detected at the border between the left and right hemilivers, and another lesion of 51 × 109 mm was detected in the right posterior section. The portal venous-phase and delayed-phase scan showed a clear profile, filling defect in the right hepatic vein and ascending to the inferior vena cava; the middle hepatic vein was invaded by the tumour. In addition, the portal vein of this patient had type II variation (the main portal vein was first issued with the right posterior branch, which was further divided into the left branch and right anterior branch), which increased the difficulty of stage-one surgery (Figs. and ).
This patient was divided into III B (T3bN0 M0) at the TNM Classification of Malignant Tumours, which was not considered surgically treatable; Barcelona Clinic Liver Cancer (BCLC) stage is in stage B, and transcatheter arterial chemoembolization (TACE) treatment is recommended according to the guidelines. ALPPS has become a new choice for this patient to achieve R0 resection.
The patient was diagnosed with chronic hepatitis B for the first time after admission. The HBV DNA titre was 1.82 × 107. Therefore, we administered entecavir 0.5 mg once a day as antiviral therapy, with no other special treatment before surgery.
The stage-one operation was performed on April 14, 2018. After successful anaesthesia, the patient was kept in a supine position, followed by routine disinfection, draping and insertion of a Veress needle and injection of carbon dioxide gas (14 mmHg). Then, the conventional operative hole was made for delivery laparoscopy and the operating instruments, which were operated on by the three-port method. The exploration showed no ascites, mild liver cirrhosis or giant hepatocellular carcinoma in the right lobe of the liver with partial growth outward. In addition, intraoperative ultrasonography revealed hepatocellular carcinoma located in S8 and S4 of the liver, as well as the left hepatic vein branch. With the marking of the splitting route of the liver within the above sites, the ligamenta teres hepatis and falciform ligament were cut off, in combination with the removal of the gallbladder. Subsequently, the right hepatic portal was dissected, and the right posterior and anterior branches of the portal vein were separated and ligated from the right incisura of the hepatic portal. The liver parenchyma was separated by an ultrasonic knife along the marked route. Following blocking of the hepatic hilum, the liver parenchyma was cut off 1 cm away from the right side of the falciform ligament in an incision manner from the top to the bottom and from shallow to deep. Afterwards, the S4 branch of the left hepatic vein and Glisson’s capsule were both ligated. With complete haemostasis, biological protein glue was sprayed on liver sections, followed by isolation with an anti-adhesion absorbable membrane. The drainage tube was placed and fixed, and the instrument and dressing were counted without mistakes. After that, the incision was sutured layer by layer. The hepatic portal was blocked twice during the operation, for 15 min each time (Fig. ).
The gastric tube was removed on the first day after the operation, and the patient consumed fluids and walked on the second day after the operation. The liver volume was assessed on the sixth day after the first-stage operation. The volume of the liver in the left lateral lobe was 427.7 ml, an increase of 54.5%, and the FLV/SLV was 37.8%. Furthermore, the volume of the liver was re-evaluated on the tenth day after the operation. The volume of the left lateral lobe was 511 ml, which was an increase of 85%, and the FLV/SLV reached 45.13%.
The second-stage surgery was performed on the twelfth day after the first-stage surgery. With successful anaesthesia, the patient was kept in a head-high and feet-low lithotomy position. After routine disinfection, draping and insertion of a Veress needle and injection of carbon dioxide gas (pressure of 14 mmHg), the conventional operative hole was established for the placement of robot-assisted laparoscopic lenses and operating instruments, which were operated by the five-port method. The puncture device was arranged in a C shape. Exploration under the microscope showed a small amount of ascites, new adhesion of the omentum around the hepatic portal, slight tissue oedema, obvious enlargement of the left lateral lobe of the liver, no obvious change of the right lobe of the liver and its internal tumour and separation of the left external lobe splitting incision. Following separation of adhesions, the greater omentum adhering to the right lobe tumour was dissected, followed by dissection of the right hepatic ligament, separation of the right hepatic artery and cutting off after ligation. Intravenous injection of ICG (5 mg) was applied with successful development of the left lateral lobe; however, the right third lobules did not develop. Afterwards, the right anterior and posterior branches of the portal vein were separated, and the right hepatic duct was separated, clipped and then removed. Right and upward separation was carried out from the liver incision along the inferior vena cava surface. After ligating the short hepatic vein and separating the root of the middle hepatic vein, the left hepatic vein was clipped and cut following protection. Subsequently, the right hepatic vein was separated from the right side, and the right hepatic vein was cut apart, followed by ligation of the right inferior phrenic vein. Part of the right coronary ligaments that were not disconnected was then separated, and the right third lobules were removed. After a small incision was made in the lower abdomen, the specimen was extracted, the incision sutured and the pneumoperitoneum re-established. Finally, with complete haemostasis of the wound, the incision was irrigated, and two drainage tubes were placed. In the last step, the incision was closed layer by layer after confirmation of the instrument and dressings (Fig. ).
Surgical results: The duration of the first and second operations lasted 191 and 227 min, respectively. Intraoperative bleeding was 50 ml, and there was no blood transfusion in either operation. Postoperative pathological results were reported as moderate and poorly differentiated hepatocellular carcinoma, without tumour tissues at the margin of incision.
Before stage one, we performed 3D reconstruction of the CT results by using the Hisense Computer-Aided Surgery system, and the liver volume of the patients was 1267.4 ml. If the right and left hepatic lobes were removed along the margin of the tumour capsule, the remnant liver volume was 276.9 ml, and the RLV/SLV was 24.45%. After 11 days of stage-one surgery, we performed 3D reconstruction again. The patient’s left lateral section of the liver was 511 ml, which was an increase of 85%, and his future liver volume over the standard liver volume was 45.1% (Figs. and ). The last laboratory examination was on March 11, 2019. Elevation of liver enzymes was minimal, the HBV DNA titre was 36.7 IU/ml and alpha fetoprotein was 63.37 μg/l.


A 74-year-old female with hypertension, diabetes mellitus, chronic kidney disease and recently diagnosed rheumatoid arthritis who immigrated to the United States one year prior from Bangladesh presented with malaise, nausea, diarrhea, chills and decreased appetite. For the past six months since being diagnosed with rheumatoid arthritis, she was treated with prednisone and methotrexate, which she could not tolerate due to gastrointestinal side effects. Methotrexate was stopped and switched to leflunomide; however, the patient then developed transaminitis and thrombocytopenia to 60s. In either case, both disease-modifying anti-rheumatic drugs (DMARDs) failed to induce remission in her disease and were stopped due to intolerance. Adalimumab was started along with prednisone leading to successful control in her disease.
Two months after adalimumab was initiated, the patient presented to the emergency department as febrile to 39.7 C and was admitted to the hospital with fever of unknown origin. No signs of arthritic flare were present on our physical examination. Laboratory studies revealed leukopenia (3.39) with an absolute neutrophil count of 1460 and 22% bands, thrombocytopenia (54), anemia [hemoglobin (Hb) 9.8, hematocrit (HCT) 29.6] with a positive Coombs test, high inflammatory markers [C-reactive protein (CRP) 60.7], low fibrinogen (97), markedly elevated ferritin (87.718), transaminitis (AST 201, ALT 61 with negative HAV, HBV, undetectable HCV RNA quantitative assay), high IL-6 (63.7), lactate dehydrogenase (LDH) (above 900 IU/L) and d-dimer (34.089). She was started on broad-spectrum antibiotics and intravenous methylprednisolone, but extensive infectious work-up (including blood and urine cultures, EBV and Quantiferon-TB) failed to reveal a particular source. COVID-19 was twice negative, and a negative chest computed tomography angiography (CTA) and lower extremity Doppler made venous thromboembolism unlikely. Occult malignancy was ruled out with negative computer tomography of the chest, abdomen and pelvis. Rheumatological work-up included a positive antinuclear antibody (ANA 1:320, speckled pattern) with negative anti-double stranded DNA, negative anti-Smith antibodies and normal complement levels (C3 complement 124, C4 complement 58). Although anti-histone antibodies (6.3, ref. range 0.0-0.9 units) were positive, the patient continued to be febrile and pancytopenic despite steroid therapy, therefore we deemed drug-induced lupus less likely given normal complement levels. In addition, the patient displayed nephrotic-range proteinuria (4.3 g/L) with worsening of her baseline kidney function (creatinine 2.5, from baseline 2.0) and kidney biopsy showed glomerulosclerosis without signs of lupus nephritis or amyloidosis, and stained negatively under Congo red. Anti-neutrophil cytoplasmic antibodies (c-ANCA and p-ANCA) were negative. Of note, patient’s fasting triglycerides were elevated at 217 mg/dL, and soluble CD25 returned high at 4.363 (ref. range 175-858 pg/mL). Given refractory laboratory abnormalities meeting five out of eight diagnostic criteria for MAS/HLH [] - hyperferritinemia, elevated fasting triglycerides, pancytopenia, hypofibrinogenemia and high soluble CD25 - bone marrow biopsy was performed. Pathology confirmed hemophagocytosis with focally prominent histiocytes, many containing cellular debris and phagocytosed red blood cells. A diagnosis of macrophage activation syndrome was made and therapy was initiated with dexamethasone and etoposide [].


An 18-year-old Caucasian male with FXS, ADHD, IDD, and ASD diagnosed in childhood was referred by his pediatric neurologist to the psychiatric clinic for evaluation of sudden onset psychosis, catatonia, and behavioral changes. The patient was diagnosed with FXS at birth. Due to having a severe global developmental delay, he was enrolled in an early intervention program and a special education program at his school. The patient has four other siblings, two of his older brothers have FXS and ADHD. The patient’s mother is a carrier for the FMR1 gene and has diagnoses of ADHD, anxiety, and depression. The maternal grandfather was also diagnosed with FXS. The patient’s father has a history of bipolar disorder type 1 and post-traumatic stress disorder. In the month prior to psychiatric evaluation, the patient presented with agitation, aggressiveness, and anger towards family members leading to the patient being isolated in his room. Irritability, insomnia, crying spells, and mood swings were also present. Auditory and visual hallucinations were reported. The patient was seeing people around him and he was talking to them. He also had a fear of someone being behind his back. The patient experienced a loss of basic learned skills including holding a pen, writing, and drawing.
Catatonia including standing in one position with limited movements and limited blinking, staring at the ceiling for prolonged periods of time, waxy flexibility, posturing, stereotypies, echolalia, mutism, and cog-wheel rigidity were noticed. According to his parents, the patient used to be a “sweet, friendly boy” who now is “a very different kid” who is very difficult to manage at home.
Before the psychiatric evaluation, the patient was hospitalized for 12 days in a medical hospital. Vital signs were normal. On neurological examination, severe cog-wheel rigidity in all extremities, bilateral downward-pointing toes, bilateral hands clenched in flexed position, and stiffness with rigidity of the entire body were noted. During the hospital course, all the labs and imaging were normal as can be seen in Table . Treatment included a benzodiazepine challenge test, quetiapine, and diphenhydramine with no improvements. The patient was discharged with outpatient psychiatric follow-up.
Course and treatment
On his first visit to the psychiatric clinic, the patient had been taking quetiapine 150 mg daily and lorazepam 4 mg daily for 30 days without any improvement. On examination, patient was noted to have cog-wheel rigidity, muscle stiffness, and dystonia. He was internally stimulated, and his mood and affect were irritable and anxious. Lack of cooperation and rapport was seen. He was complaining of low back pain due to severe dystonia in his back and chest.
Lorazepam was changed to clonazepam 1 mg twice a day per oral, divalproex sodium 250 mg per day was started, and quetiapine was continued.
On his two-week follow-up, the patient had mild improvement, but he was still isolated from the family due to aggression. Due to the patient's continued symptoms, the patient’s mother decided to initiate lisdexamfetamine 50 mg daily from patient’s older brother’s prescription, which significantly improved the patient’s aggressive behavior. She felt comfortable making this change as she has two other children with the same diagnoses; however, she did report this medication change immediately and has been compliant with her sons' medications after this with no concern for abuse. She was counseled at the follow-up appointment that lisdexamfetamine is a Schedule II substance and should not be started without consultation with a physician. Due to the improvement of symptoms, the dose of divalproex sodium was titrated up to 1000 mg daily and clonazepam was decreased to 0.5 mg twice daily, while quetiapine 150 mg daily and lisdexamfetamine 50 mg daily were continued as before.
At his four-week follow-up, the patient was on the combination of lisdexamfetamine, divalproex sodium, quetiapine, and clonazepam 2 mg daily with marked improvements in psychosis, catatonia, behavioral change, aggression, irritation, and insomnia. His parents reported that the patient was back to his normal self. The patient was no longer isolated from his family and was participating in social activities with them. On physical and mental examination, there were no signs of dystonic positioning, but mild cog-wheel rigidity continued to be noted in the upper extremities. The patient was following commands and had good eye contact with appropriate affect.
The patient continues to be monitored at the psychiatric clinic regularly and has not had a recurrence of symptoms.


A fit and healthy 52-year-old Caucasian female was referred to the Eye Casualty by her GP with a one-week history of blurred vision. At presentation, the patient’s visual acuity was 6/9 in the affected right eye and 6/6-2 in the unaffected left eye. Dilated fundoscopy examination revealed a typical presentation of right inferotemporal BRVO with a wedge-shaped distribution of intraretinal haemorrhages (Figure ), while optical coherence tomography (OCT) demonstrated significant macular edema (Figure ). Her intraocular pressure was found to be within the normal range.
Subsequently, she was treated initially with three intravitreal injections of aflibercept 40 mg/ml (Eylea®, Bayer, Leverkusen, Germany) followed by a further five injections administered as per clinical response over the subsequent 12 months. She was investigated for general risk factors for BRVO; a general screening was carried out in primary care including a battery of routine blood tests. Blood glucose, lipids, cholesterol, triglycerides and blood pressure were all found within the normal range. The patient was a non-smoker with no pre-existing health conditions; she denied any history of systemic disease. There was no relevant family history.
Interestingly, during the course of her ocular treatment, she developed acute dyspnea and was admitted under the respiratory team, eight months following initial presentation with BRVO. The patient was initially treated with broad-spectrum intravenous antibiotics and intravenous fluids for suspected infective pneumonia. As several courses of intravenous antibiotics did not resolve her symptoms, she was investigated with a thorax CT, which showed evidence of ILD. The patient was reviewed by the rheumatology team; she denied any rheumatological symptoms except for Raynaud’s phenomenon and had no obvious features of myositis. Nonetheless, a thorough investigation of myositis-specific autoantibodies (MSA) including the ASS autoantibody panel was conducted. The patient tested positive for anti-PL7 antibodies and was thus diagnosed with ASS. She was treated acutely with corticosteroids followed by cyclophosphamide and mesna intravenous infusions, which were received on a pro re nata basis as an outpatient.
Regarding her other further investigations as an inpatient, the myeloma screen was reported normal. However, alanine aminotransferase level was raised at 90 u/L, and C-reactive protein was found elevated at 34 mg/L.
Historically, ASS was not considered a separate entity and was in fact regarded as a subset of DM or PM depending on their clinical presentation. However, in this case, the patient was reviewed by the rheumatology team and found to have little features of DM, but was described to have Raynaud’s phenomenon with no particular signs of scleroderma. Although the prevalence of ILD (86%) is more common than that of myositis (76%) in ASS, myositis usually presents earlier than ILD []. Occasionally, the symptoms of ILD such as dyspnoea can be the first presenting symptom, with an estimated 33% of ASS patients presenting with ILD preceding myositis [].
The diagnosis of PM/DM would usually be done by electromyography (EMG) and is associated with elevated muscle enzymes serum creatinine kinase and aldolase levels, which were normal in this clinically amyopathic patient. As ASS may present without myositis, it is important to be aware of the diagnostic criteria (Table ; adapted from Witt et al., 2016) [].
Regarding treatment for her ophthalmic condition, she was managed with a course of three monthly anti-vascular endothelial growth factor (anti-VEGF) intravitreal aflibercept 40 mg/ml injections. This was followed by a further course of bimonthly injections over 12 months, to maintain dry macula and excellent visual acuity. Visual acuity improved gradually during the course of aflibercept injections, with binocular vision restored to 6/6 within one year. During a review six months after the last injection, the patient was noted to have a stable vision in both eyes.
Systemically, corticosteroids and immunosuppressants are the pillars of ASS management; however, a subset of patients will be refractory to steroids. Our patient continues to be under rheumatology follow-up for ASS monitoring.


A 74-year-old, right-handed Asian man with 4 years of education was admitted to ophthalmology clinic for cataract refractive surgery. The patient suffered episodic memory decline over the past 3 years and prior neuropsychological assessment performed 2 years before this visit revealed low performance in memory on the Seoul Verbal Learning Test that was 3%tile score below 1.5 standard deviations from the mean of the age and education-normative values among the Korean population. The patient was not impaired in other cognitive domains. Magnetic resonance imaging (MRI) of the brain showed atrophic changes in the whole brain and bilateral medial temporal lobes and focal chronic infarction in the right cerebellum (Fig. A). The patient had been diagnosed with amnestic mild cognitive impairment (MCI) and regularly followed up for the state. The cognitive status was stable over 2 years. The patient had hypertension, diabetes mellitus, and dyslipidemia. Before the cataract operation, one drop of 1.0% of cyclopentolate was administered to patient's eyes. One hour after the instillation of eye drop, the patient got confused and showed abnormal behavior. The patient tried to remove the peripheral venous line and became aggressive to medical staff. The patient was referred to Department of Neurology and the elemental neurological examination revealed no abnormality. Two hours after the event, the Korean version of Mini-Mental State Examination (K-MMSE) was performed and the score was 16 of 30 which had been 26 of 30 on previous test. The patient began to recover 5 h after the onset of symptoms and the cognitive function was reverted to previous state within 24 h. 18F-flutemetamol positron emission tomography (PET) scan performed 2 months after the event demonstrated multifocal amyloid deposits in bilateral frontal lobes, the left precuneus, and the right lateral temporal cortex (Fig. Band C).


We present the case of a right-handed 90-year-old healthy and independent man who developed the sudden onset of isolated, painless, and intermittent horizontal diplopia. The separation of images had no gaze preference and was triggered by staring, such as watching television or looking at a close object. He denied the presence of any other brainstem symptoms such as vertigo, dysarthria, dysphagia, symmetric or asymmetric sensory symptoms, or ataxia. There was an absence of fatiguability in the afternoon.
His past medical history was unremarkable and he took no prescription medications. On examination, his blood pressure was 121/78 mmHg, and he had a heart rate of 82 beats per minute. He was 6 feet tall and weighed 140 pounds. His gait was wide-based and he used a cane. He was able to tandem-walk with assistance. Romberg sign was absent. Cognitively, he was sharp with focused and non-hesitant rapid response to questions. His speech was fluent without dysarthria, but with mild hypophonia.
Cranial nerve examination revealed full ocular motility in all directions without ptosis or pupillary abnormalities. Visual fields were full to confrontation without visual neglect by sequential visual field testing. The rest of the cranial nerve function was normal. Power was normal and deep tendon reflexes were surprisingly lively but without spasticity. Coordination testing revealed a mild intention tremor in both upper extremities. Sensory examination revealed a mild loss of vibratory sense in his big toes.
An MRI study with diffusion-weighted imaging (DWI) sequence revealed a left posterior parietal cortical ischemic infarct (Figure ).
A cardiac event monitor revealed paroxysmal atrial fibrillation one week after the onset of the cerebral ischemic infarct (Figure ).
A carotid duplex scan and a transcranial Doppler study of the cerebral circulation revealed no flow-limiting vascular lesions. Due to the embolic nature of the cortical ischemic infarct, demonstration of atrial fibrillation, and his advanced age of 90 years, the patient was started on low-dose apixaban 2.5 mg twice daily. He refused a referral to a cardiologist or an optometrist/ophthalmologist despite encouragement to do so.


A 74-year-old female patient presented to the emergency department of Kyung Hee University Medical Center because of dizziness and generalized weakness that started 2 days prior. The patient had a history of old cerebral infarction and was taking oral medications for hypertension and dyslipidemia. Brain magnetic resonance imaging (MRI) revealed an acute focal infarction in the right basal ganglia. At that time, in the laboratory examinations, the erythrocyte sedimentation rate (ESR) was 74 mm/h (normal range, <20 mm/h) and C-reactive protein (CRP) level was 6.61 mg/dL (<0.5 mg/dL) Aspirin was prescribed to the patient. One month later, the patient was admitted to our neurology clinic because of weakness in her left arm and numbness in both hands. MRI revealed no diffusion-restricted lesion in the brain. Physical examination revealed no remarkable findings except for paresthesia in the left hand. The patient’s motor power of four limbs were normal (grade 5). Her initial chest radiograph was normal. Her laboratory examination results showed a white blood cell count of 9.79 × 109/L (76% neutrophils), ESR of 120 mm/h, and CRP level of 18.44 mg/dL. However, she had no fever. Her serum creatinine level (0.92 mg/dL) and estimated glomerular filtration rate (GFR; 63.59 mL/min per 1.73 m2) were within the normal ranges. No proteinuria was identified. Chest computed tomography (CT) and abdominal CT were performed to exclude hidden malignancy. Chest CT revealed a subpleural nodule measuring approximately 1.5 cm in the right lower lobe. Abdominal CT revealed multiple small ill-defined low-attenuated lesions in the spleen nodules (). Her thrombophilia screening test result was negative. The Padua prediction score was 2, in the low risk.Her echocardiography was normal and 24-hour Holter monitoring revealed normal sinus rhythm. Nerve conduction tests revealed sensorimotor polyneuropathy. The myeloperoxidase (MPO)-ANCA test result was positive (5.10 index). Percutaneous needle biopsy of the pulmonary nodule was performed first; however, the pathological results showed only focal acute inflammatory cell infiltration, with no evidence of malignancy. The second biopsy of the sural nerve demonstrated perivascular inflammatory cell infiltration and necrotizing vasculitis. These findings were consistent with vasculitic peripheral neuropathy. By considering the results of the MPO-ANCA test and the pathological profile of the sural nerve, the patient was diagnosed as having MPA-associated neuropathy with a splenic infarction and pulmonary inflammatory nodule. She received steroid pulse therapy (methylprednisolone, 125 mg/day for 3 days) on day 20 of hospitalization, followed by cyclophosphamide (500 mg/m2 every 4 weeks for six doses) with steroid maintenance therapy. She showed improvement after the steroid therapy. Her ESR level decreased to 49 mm/h and the CRP level decreased to 0.5 mg/dL. The peripheral numbness subsided slowly. After 1 month, the patient’s pancreatic enzyme levels (amylase, 192 U/L (23–85 U/L) and lipase 346 U/L (0–160 U/L)) were elevated without abdominal pain. Abdominal CT was performed to evaluate for pancreatitis and revealed improvement of the splenic lesion such as the infarction. The patient had an uneventful course for 5 months after the treatment.This study was approved by the Institutional Review Board (IRB) of Kyung Hee Medical Center, and the requirement for informed consent was waived (IRB 2020-12-083).


Our patient is a 53-year-old female, who initially presented to the hospital’s ED after a motor vehicle accident. During her evaluation, she had a chest X-ray performed, which showed an incidental right-sided chest wall tumor, as shown in Figure . This was followed by a CT thorax, which showed a 3.3 cm x 1.5 cm pleural-based mass-like density, as shown in Figure .
After this, an ultrasound of the chest was performed to evaluate for hemothorax; however, the ultrasound imaging did not demonstrate any pleural fluid collection.
On follow-up in the clinic, the patient reported right-sided pleuritic chest pain. She did not report any cough, dyspnea, or history of previous pulmonary disease (including pneumonia or tuberculosis). She was a lifelong nonsmoker and had no asbestos exposure.
The patient was referred for a CT-guided biopsy of the pleural tumor -- the biopsy showed spindle cell proliferation, with features indicating SFTP. Figure shows the spindle cells with interposed collagen. Additionally, immunohistochemical stains of the biopsy sample were positive for CD34, CD99, and vimentin. The positive CD34 stain is shown in Figure .
The patient was referred to cardiothoracic surgery for tumor resection.