A 33-year-old married Indonesian male handyman with no significant past medical and psychiatric history presented to the emergency department of a type-C class rural hospital with partially amputated penis after sustaining a mechanical grass cutter injury six hours prior to the hospital visit. Pre-operation assessment in the emergency department was limited to penile amputation only, as we were unable to clearly define structural damages due to diffuse bleeding and excessive pain. At the time of patient arrival, trauma resuscitation protocol including airway, breathing, and circulation assessment was running. The patient was also given antibiotic anti-tetanus, blood specimen testing and on a 23G IV line to handle the earliest signs of shock if necessary. Although compression was immediately performed on the wound, bleeding still persisted (
).
At presentation, his vital signs showed blood pressure of 100/60 mmHg and heart rate of 100 bpm. Physical examination showed an amputated penis with diffuse bleeding. The detailed dorsal structures and urethra could not be evaluated properly. His scrotum and testicles were found to be intact. Laboratory tests were within normal values with a hemoglobin value of 14.5 g/dl.
Fluid infusion and antitetanic injection were administered and the patient was given emergency surgical management by the attending urologist. The patient was placed in the supine position and underwent general anesthesia with 200mg propofol, 50mg atracurium, 10mcg fentanyl, oxygen gas 1 liter/minute, and N2O 1 liter/minute. Saline irrigation bath was performed on the wound to allow visualization of all damaged structures. Surgical exploration revealed a complete detachment of cavernosal bodies, along with superficial and deep dorsal veins, dorsal and deep artery, and nerves injury. The spongiosal body sustained a partial rupture. The urethra was then found to be intact – no urethral mucosa was visualized – allowing insertion of a 16Fr foley catheter. The catheter was able to pass through without any resistance and therefore did not require any repair. Under loupe 2.5x magnification, the spongiosal and cavernosal bodies were sutured circumferentially at both ends with a vicryl 5-0 interrupted suture, followed by suturing the buck’s fascia with the skin with a vicryl 4-0 interrupted suture, followed by application of a pressure bandage. The deep arteries, dorsal arteries and nerve, and the superficial and deep dorsal veins were anastomosed with the available 2.5x loupe magnification. The surgery was completed within two hours and 15 minutes with total ischemia time of nine hours (
).
The patient was put on total bed rest until the third day post-surgery, with administration of intravenous 3
rd generation cephalosporine antibiotics (ceftriaxone 2gr/day), an analgesic (Ketorolac 25mg twice a day), and penile phototherapy (six hours a day) for five days. On the 3rd day after surgery we applied a new sterile dressing on the wound and observed no significant edema or pus or any leakage. On the fifth day after surgery, we adopted a post operative open wound treatment care plan. The catheter was also removed at the 5th day post surgery with close observation for hematuria or urinary retention. Five days after reconstruction, the penis showed no significant edema and swelling of the distal penile shaft, and sensation started to return gradually. The patient also underwent doppler ultrasound on day five to assess vascularization of penile distal to the injury. Evaluation with Doppler ultrasound showed adequate deep and superficial arterial flow at the distal end of the penis. On the fifth day post-surgery, the patient was discharged without urethral catheter following spontaneous micturition without difficulty in voiding (
).
One month after reconstruction, the patient underwent further evaluation at a urologic clinic with good skin preservation and adequate wound healing. The patient was also evaluated with the International Prostate Symptom Score (IPSS) of 2, the International Index of Erectile Function (IIEF) score of 19, Quality of Life (QoL) score of 1, and Erection Hardness Score (EHS) grade II–III rigidity, along withfine penile sensation. There was no urinary fistula formation or difficulties in voiding. The patients felt satisfied with his condition.


A 61-year-old male was admitted in November 2019. Seven years prior, the patient's hands began turning white, and he experienced cyanosis with pain in his hands. He reported that his fatigue gradually increased starting 5 years prior. One year prior, the skin on the fingertips of both hands began to break. The patient was treated at a local hospital. His blood pressure was approximately 160/100 mm Hg, urinalysis revealed protein (+1) and blood (+2), his serum creatinine level was 76 μmol/L, his albumin level was 32.8 g/L, and his globulin level was 43.6 g/L. He was positive for ANA (1:640), anti-SM antibody, anti-SSA and anti-Ro-52 antibodies. His C3 level was 0.75 g/L (0.9–1.8), his C4 level was 0.11 g/L (0.1–0.4), and his ESR was 66 mm (0–15). Chest CT showed bilateral pulmonary fibrosis. Three months after treatment at the local hospital, edema began to develop in his lower limbs; this edema worsened gradually and was accompanied by chest tightness, asthmatic suffocation, and an inability to lie flat at night due to dyspnea. At that time, the patient's blood pressure had increased to 220/130 mmHg, his urine protein level was 6.7 g/d, his serum creatinine level had increased from 92 to 299 μmol/L, his albumin level was 28.1 g/L, his globulin level was 35.4 g/L, his LDH level had increased to 486 U/L (114–240), and his NT-proBNP level was markedly elevated at over 35000 ng/L (0–900 ng/L). Echocardiography showed left atrial enlargement and pulmonary artery hypertension (PAH). Methylprednisolone was given at a dosage of 40 to 80 mg/d, and antihypertensive and diuretic therapy regimens were administered. There were no typical symptoms of SLE, such as rash, alopecia, photosensitivity, oral ulcer, or arthralgia.
The patient's blood pressure was 190/115 mm Hg. His facial skin was swollen and stiff, with a sharp nose, fewer wrinkles and atrophic lips (Fig. A). Both hands were swollen and stiff, and the fingertips of the forefingers and middle fingers showed ulceration with scabs (Figs. B and 1C). No damage was found on the trunk or upper limbs. Slight symmetrical depressed edema could be seen in both lower limbs.
Routine blood tests showed that his white blood cell count was 12.83 × 109/L, his hemoglobin level was 8.7 g/dL, his platelet count was 135 × 109/L, and his reticulocyte percentage was 2.28% (0.5–1.5). Broken red blood cells were present in peripheral blood smears. His urine protein level was (+3), the urine sediment showed deformed hematuria, and his 24-hour urine protein level was 9.7 g. His serum creatinine level was 337.1 μmol/L, his albumin level was 27.2 g/L, his globulin level was 21.8 g/L, his TG level was 2.2 mmol/L (0–1.7), his TCHO level was 6.99 mmol/L (3.1–5.2), and his UA level was 523 μmol/L (208.3–428.4), with normal serum ions and hsCRP. Arterial blood gas analysis showed hypoxemia. The serum levels of IgA, IgG and IgM were normal; his ESR was 20 mm; his C3 level was 0.64 g/L (0.7–1.4); and his C4 level was normal. His ANA titer was 1:1000 and he was weakly positive for anti-SSA antibodies and strongly positive for anti-Ro-52 antibodies; however, he was negative for anti-dsDNA, anti-SM, anti-SSB, anti-RNP, anti-ScL-70, anti-GBM, and ANCA. His level of serum RF was normal, and the tests for aCL, anti-β2-gp1 and lupus anticoagulant were all negative. Coombs’ test was weakly positive. Chest X-ray and CT showed pulmonary interstitial lesions (Figs. A and 2B). Echocardiography revealed severe pulmonary hypertension and double atrial enlargement (right atrium was 34 × 51 mm) with an EF of 61%. Pulmonary function tests showed a normal ventilation function but a severe decline in diffusion function. Serum protein electrophoresis and serum and urine immunofixation electrophoresis were normal, and there was no visible monoclonal immunoglobulin. Grade III hypertensive retinopathy could be seen on fundoscopy.
Renal biopsy was also performed (Fig. ). The results confirmed the diagnosis of lupus nephritis (LN) class V (Fig. A, B, C, D) and TMA. It was observed that the walls of the renal arterioles were thickened, especially those of the interlobular arteries, which generally had mucinous edema and endometrial fibrosis resembling “onion bulbs” (Fig. E), and the lumen was narrowed to the point of occlusion. The loose layer of the glomerular basement membrane was widened, as observed on electron microscopy (Fig. F).
The final diagnoses were SSc-SLE overlap syndrome, SRC (SSc-TMA), lupus nephritis class V, malignant hypertension, PAH, congestive heart failure, and hemolytic anemia. The patient was treated with prednisone (40 mg/d), cyclophosphamide (50 mg/d), renin-angiotensin system (RAS) inhibitors, diuretics, and acetylcysteine. After a month of therapy, the patient's blood pressure had decreased to below 140/90 mm Hg, his serum creatinine level had decreased to 293.0 μmol/L and his albumin level had increased to 31.1 g/L. His urinary protein and NT-proBNP levels did not change. Ultimately, the patient died suddenly of heart failure on the 35th day after discharge.
Informed written consent was obtained from the patient for the publication of this case report and the accompanying images.


A 26-year-old male admitted in emergency room for abdominal pain of 5 days after dragon boat race, localized in the epigastrium and upper left quadrant, associated with chest tightness and vomiting. There was no associated cough, dyspnea, fever, or jaundice. No similar episodes had been reported previously. His history revealed that he had a knife wound to the left lower chest 10 years before in a fighting; however, more detail information is unclear. There were no recent taken medications, no known history of alcohol abuse or gallstones. On examination, no fever and icterus was present, but with a tachycardia of 115 beats/min. His respiratory rate was 22 breaths/min with decreased breath sounds at the left lung base. A soft compressible mass was palpable in the epigastrium with mild tenderness in the left hypochondrium, but no guarding or rebound tenderness. Laboratory workup revealed amylase levels (780U/L) that were elevated 3 times above normal, combined with abdominal pain, suggesting AP. White blood cell count 17.84 × 109/L. Total and direct bilirubin, serum calcium, and lipid levels were within normal range. In addition, other etiology for AP, including history of alcohol/drug intake, was negative. The etiology of AP was, at this stage, unknown.
A thorough review of the patient's history of knife wound, there was little information available to aid diagnosis. Therefore, a computer tomogram scan of chest and abdomen was performed the same day, which not only confirmed the presence of AP with inflammation of the peripancreatic fat but also revealed a rare case of a pancreatic volvulus secondary to gastric herniation into the thoracic cavity. Thoracoabdominal CT (Fig. , oblique coronal view) showed intrathoracic stomach herniation through the left diaphragmatic defect (red arrows), meanwhile, bulky and folded into a “Ω” shaped pancreas closed to the diaphragmatic defect (yellow arrows). Abdominal CT (Fig. , axial view) showed the head of pancreas displaced into the left epigastrium, posterior to the left lobe of liver (red arrow), and fat stranding surrounding the swelled body and tail of the pancreas (yellow arrow). Combined with abdominal pain and increased amylase (780 U/L) levels, suggesting AP.
The night of admission, the patient underwent emergency surgery. Intraoperatively a 5 × 4 cm size defect in the left diaphragm was found, stomach and greater omentum with partial necrosis were herniated into left thoracic cavity with underlying lung collapse. After meticulous dissection and removal of necrotic omentum, the stomach and greater omentum were reduced into the abdominal cavity, and the defect was closed with interrupted ethibond suture. The postoperative course was uneventful, and the patient was discharged from the hospital on the sixth postoperative day.


A 49-years-old man of Asian background has been hospitalized at our institution for cardiogenic shock due to acute lymphocytic myocarditis, which was diagnosed by endomyocardial biopsy (). Connected to an Impella CP and on high catecholamine doses, the patient was transported from a peripheral hospital to our institution. At admission, the patient presented with lactate > 100 mg/dl, lactate dehydrogenase (LDH) of 1,077 U/L, troponin T of 14,896 ng/L, creatine kinase of 1,590 U/L, and N-terminal pro b-type natriuretic peptide (NT-proBNP) of 2,399 ng/L. Since kidney function was impaired with anuria and a serum creatinine of 1.62 mg/dl, dialysis had to be started. On high catecholamine doses, LVEF was around 5%, while right ventricular function was visually at least moderately depressed. The cardiac index was 1.3 L/min/m2 with a pulmonary capillary wedge pressure of around 40 mmHg. We then started a V-A ECMO to obtain hemodynamic stabilization (ECMELLA-approach). After 6 days of ECMELLA, hemolysis increased significantly with plasma free hemoglobin (fHb) reaching levels above 130 mg/dl (20 μmol/L) despite reduction of the Impella CP support. To continue venting the LV, we decided to substitute Impella CP with PulseCath iVAC2L. A 30-cm-long, 18-Fr Adelante® Magnum (Oscor Inc.) sheath was inserted in the femoral artery, which had been used for the Impella access. The side port from the Adelante® was connected by sideline with the pressure transducer from the intra-aortic balloon pump (IABP) console. After iVAC2L was inserted with the distal tip into the LV cavity, the paracorporeal membrane pump was filled with heparinized saline, and a wet-to-wet connection was established with the iVAC2L catheter (). A CS100 IABP console (Maquet Cardiovascular, Fairfield, NJ, USA) was used as a driver, and triggering was done using the aortic pressure (AP) waveform (). The console was set to synchronized mode and 1:1 assist ratio. Anticoagulation was provided with partial thromboplastin time (PTT) of 80 s during MCS.
The main results obtained were the following: increase in LVEF from 10% to about 20%, reduction in fHb to <10 μmol/L (65 mg/dl), reduction of the LV end-diastolic diameter (LVEDD) from 67 to 64 mm, and stabilization of the blood pressure in 110/60 mmHg, allowing for the reduction of the ECMO support to a minimum. There was a moderate acute reduction on LV end-diastolic pressure (LVEDP) from 22 to 18 mmHg. This was added to afterload reduction and increase in forward flow, which were evidenced by distal displacement of the watershed as contrast media became visible in the descending aorta ().
After 5 days of pulsatile support, the membrane pump, the connector tubing, and the bi-directional flow catheter were inspected, revealing no signs of thrombus formation, component disruption, or fatigue. Weaning of iVAC2L was performed according to the following steps: synchronized pulsatile flow with 1:1 assist ratio for 5 days, 1:2 for 8 h, and 1:3 for further 8 h. Hemodynamic stability without catecholamine support, central venous oxygen saturation (SvO2) > 60%, and normal lactate levels were observed throughout the weaning period. iVAC2L was set to standby mode and removed under low-dose inotropic support (dobutamine 2 μg/kg/min).


In July 2018, a 76-year-old man was referred to the oral surgery clinic from the gastroenterology and hepatology clinic for dental caries treatment. In August 2016, the patient was diagnosed with gastric cancer with multiple liver metastases and lymph node metastases. The patient began chemotherapy comprising cisplatin and tegafur/gimeracil/oteracil. In February 2017, the lymph node metastases had shrunk and the patient underwent surgery for gastric cancer. Subsequently, beginning in June 2017, he started chemotherapy comprising paclitaxel (100 mg) and ramucirumab (310 mg) as second-line treatment. Paclitaxel was given weekly, and ramucirumab was given every 2 weeks. The patient was also prescribed concomitant antihypertensive and diuretic medications. In July 2018, there was no evidence of recurrence of liver metastasis by positron emission tomography. Furthermore, the patient desired to treat dental caries and stop chemotherapy; thus, chemotherapy was discontinued. Thirty days after the last dose of ramucirumab, the right maxillary central incisor, right maxillary second premolar, left maxillary first and second molars, and left mandibular lateral incisor were extracted (). The postextraction course was uneventful with good healing of tooth extraction sockets. In November 2018, computed tomography showed recurrence of liver metastasis and the patient restarted chemotherapy with paclitaxel and ramucirumab (same dose as before). In January 2019, the patient experienced repeat pericoronitis in the right mandibular third molar and eating difficulties. Thus, the right mandibular third molar and right mandibular first molars and second premolar, which were difficult to treat conservatively, were extracted in March 2019 without ramucirumab discontinuation after discussion between the patient and the chemotherapy team. The extractions were performed 8 days after ramucirumab administration, taking into consideration the half-life of ramucirumab (8 days) and the timing of the next administration of ramucirumab. The third molar, which was an impacted tooth, was extracted with elevation of the mucoperiosteal flap and bone removal. After the tooth extractions, the patient received amoxicillin (750 mg) for 7 days, and acetaminophen (400 mg) was given as an analgesic. Seven days after the extractions, the patient felt strong contact pain in the sockets. He had no other symptoms that suggested the spread of inflammation. Dry sockets were strongly suggested, and the analgesic was continued. Paclitaxel and ramucirumab were restarted according to the chemotherapy regimen. Twenty-three days after the extractions, the patient stated that he was still in severe pain but the pain was better than before (). Subsequently, paclitaxel and ramucirumab were continued. Twenty-five days after the extractions, the lower denture was extended to cover the extraction socket to decrease the contact pain. Forty-seven days after the extractions, the pain was moderately diminished, but soft tissue did not completely cover the extraction sockets. Sixty-one days after the extractions, the pain was considerably diminished, and soft tissue mostly covered the extraction sockets of the first molar and second premolar, but not that of the third molar (). This was probably because the third molar extraction was more invasive with bone removal. Seventy-five days after the extractions, the socket of the third molar was slightly covered with soft tissue (). One hundred and three days after the extractions, the socket of the third molar was still not completely covered with soft tissue. One hundred and seventeen days after the extractions, the socket of the third molar was partially covered with soft tissue. There was almost no contact pain. By comparison, the extraction sockets of the first molar and second premolar were completely covered with soft tissue (). One hundred and thirty days after the extractions, the extraction socket of the third molar was almost completed covered with soft tissue with almost no pain (). On the same day, the final doses of paclitaxel and ramucirumab were given because the patient's liver metastasis subsequently progressed. Third-line treatment with nivolumab (240 mg) was started 158 days after the tooth extractions, and the patient reported no pain in the sockets at this time. One hundred and eighty-four days after tooth extractions, the patient continued to receive nivolumab, and complication of the socket such as bone exposure was not observed.


An eleven-year-old male, castrated, 47.2 kg Labrador Retriever presented to the Virginia-Maryland College of Veterinary Medicine Veterinary Teaching Hospital (VTH) in November 2018 for placement of a urethral stent. The patient had been diagnosed with transitional cell carcinoma via traumatic catheterization in January 2018, for which he had been seen monthly at the primary referral veterinary center to receive routine ultrasound examinations and chemotherapy (mitoxantrone 6.2 mg intravenously monthly) through October 2018. Over time the patient developed stranguria and there was evidence of thickening of the prostatic urethra in addition to a tumor present in the trigone. At presentation to the VTH, the patient was receiving piroxicam 17 mg q24h PO, milk thistle 175 mg q24h PO, S-adenosyl-methionine 400 mg q24h PO, omega fatty acid supplement 1600 mg q24h PO, and a vitamin B12 supplement.
From the time of initial diagnosis, routine monthly CBCs had been performed with no major abnormalities detected. Biochemical screening had been performed intermittently, with serial monitoring of BUN and Creatinine during chemotherapy treatment. At presentation for placement of the stent, the patient’s most recent bloodwork showed a slightly elevated BUN at 30 mg/dL (Reference Interval (RI) 7–27), elevated ALT at 159 U/L (RI 10–125), elevated ALKP at 981 U/L (RI 23–212), a slight neutrophilia at 13,110/μL (RI 2950-11,640), urine specific gravity 1.027, and a moderate amount of both blood and protein on free-catch urinalysis. Remaining values were unremarkable and within normal reference ranges. Physical examination revealed obesity (body condition score 8/9), mild to moderate hindlimb muscle atrophy, moderate dental tartar, several epidermal collarettes across the ventral abdomen, and a prominent urethra on rectal examination; all other findings were unremarkable. Ultrasound of the urogenital tract revealed thickening of the proximal urethral wall extending cranially into the neck of the bladder, punctate hyperechoic foci throughout the prostate, and a dilated left kidney pelvis and associated ureter.
Based on these findings, it was elected to perform cystoscopy with placement of a ureteral and/or urethral stent to relieve the stranguria. The patient was fasted overnight before anesthesia. Maropitant 1 mg/kg subcutaneously was administered prior to butorphanol 0.2 mg/kg intramuscularly and an intravenous catheter was placed to facilitate anesthetic induction. Induction consisted of intravenous fentanyl 5μg/kg followed by alfaxalone 1 mg/kg to effect. Following endotracheal intubation, the patient was maintained on sevoflurane in 100% oxygen with a fentanyl continuous rate infusion (CRI) at 10μg/kg/hr. and lactated ringer’s solution (LRS) at 5 mL/kg/hr. Anesthetic monitoring included capnography, pulse oximetry, esophageal temperature, electrocardiography (ECG), fractional expired sevoflurane (FESevo), fractional inspired oxygen percentage (FiO2), and direct arterial blood pressure.
Following placement of monitoring equipment, the patient was repositioned from sternal to dorsal recumbency in preparation for cystoscopy. At this time, mean arterial pressure (MAP) declined from 61 mmHg to 40 mmHg while the heart rate began increasing from 128 beats per minute (bpm). Sevoflurane was reduced while a fluid bolus of 10 mL/kg was initiated and a dopamine CRI started at 5μg/kg/min. The blood pressure did not improve, with the MAP around 45 mmHg, and the heart rate continued to climb to 180 bpm with the appearance of intermittent ventricular premature complexes. Lidocaine 2 mg/kg was bolused intravenously and a CRI at 2 mg/kg/hr. started while dopamine was increased to 10μg/kg/min. Sevoflurane administration was discontinued and the breathing system flushed with fresh oxygen. Blood pressure began to increase to a MAP of 70 mmHg with the heart rate lowering to 100 bpm and the patient began to move slightly, so fentanyl was increased to 15μg/kg/hr. while sevoflurane was restarted and maintained below FESevo 1.3%. As the patient returned to a surgical plane of anesthesia, the blood pressure decreased again, although less dramatically to a MAP of 65 mmHg. Dopamine was increased to 12μg/kg/min and a norepinephrine CRI at 0.1μg/kg/min was started. This ultimately provided a balance that maintained blood pressure while keeping the patient adequately anesthetized for cystoscopy and allowed the dopamine to be reduced to 5μg/kg/min. The patient was moved from dorsal to left lateral recumbency and hypotension returned, but it responded more quickly to increases in dopamine and norepinephrine than previously. Once stent placement was completed, the patient was put into a sternal position in the thorax with pelvic limbs laterally, at this point the blood pressure began to rise quickly to a MAP of nearly 90 mmHg, and both dopamine and norepinephrine were discontinued.
Two days after uneventful recovery and discharge, the patient presented to the primary veterinary referral center with epistaxis and an incidental cranial mediastinal mass was diagnosed on thoracic radiographs. The client did not wish to pursue further workup and Yunnan Baiyao was prescribed for the epistaxis. However, the stranguria that resolved with the stent placement returned over the following 2 months and it was elected to re-evaluate the first stent and potentially place a second stent. No further epistaxis episodes occurred.
The presence of a mass in the chest, confirmed via radiographs following discharge from the first visit, and the decline and then improvement in hemodynamics correlating to changing body position during the first anesthetic episode, made us believe that positioning was going to play a key role in management of blood pressure in the second anesthetic episode. The patient’s condition was largely unchanged from the first physical examination, and bloodwork was similar. Coagulation parameters were normal. Cytologic evaluation of an aspirate of the mass, obtained via thoracic ultrasound, was most suggestive of thymoma as reported by a board-certified veterinary clinical pathologist, who also recommended biopsy with histopathology for confirmation. Although this was not pursued by the client, computed tomography (CT) imaging was performed to rule out presence of a nasal mass and to better clarify size and exact location of the thoracic mass with respect to major vessels and the heart.
The patient was premedicated with morphine 0.5 mg/kg and midazolam 0.2 mg/kg intramuscularly 1 h after receiving maropitant 1 mg/kg subcutaneously. Following sedation and catheter placement, induction was performed with a mixture of propofol 3 mg/kg and ketamine 3 mg/kg to effect. Propofol and Lidocaine CRIs were used for maintenance in place of sevoflurane, but the same monitoring as prior was utilized, including direct arterial blood pressure. Sternal recumbency was maintained throughout sedation, induction, and CT imaging. Due to the fast onset and short-acting vasoconstrictive effects of phenylephrine, it was administered in 1μg/kg boluses intravenously as needed for mild hypotension (MAP of 59-62 mmHg) during the early part of the anesthetic event, while the patient remained sternal. During this period, the blood pressure was responsive to phenylephrine and increased to a MAP of 65-75 mmHg shortly following boluses. The dramatic and poorly-responsive hypotension of the first anesthetic episode was not observed and the heart rate ranged from 80 to 110 bpm. CT imaging of the nasal cavity was unremarkable but it revealed a left cranial mediastinal, lobular, 7.5 cm (width) × 5.8 cm (height) × 6.8 cm (length) soft-tissue attenuating mass with an irregular fluid-attenuating central portion. It was noted to be causing rightward deviation of the cranial vena cava without direct vascular compression in the sternal position. For comparison, the heart measured 9.4 cm × 5.9 cm × 10.5 cm. Figures and illustrate a dorso-ventral and sagittal view of the mass as found on CT imaging.
Following CT imaging, the primary clinician requested left lateral recumbency for abdominal fluoroscopy and cystoscopy. As soon as the patient was re-positioned the mean arterial pressure dropped to 42 mmHg within 60 s. A dose of phenylephrine at 1μg/kg given intravenously failed to improve MAP in this instance. The patient was returned to sternal recumbency and MAP steadily increased back to its value prior to the change to lateral recumbency (MAP 63 mmHg). Ultimately the patient was maintained with the thorax sternal and the abdomen in oblique left lateral for the remainder of the procedure with no recurrent dramatic blood pressure changes.


A 58-year-old male with a history of congestive heart failure, hypertension, type II diabetes mellitus, recurrent deep vein thromboses (status post inferior vena cava [IVC] filter placement), pulmonary embolism, and hypothyroidism was admitted with neurologic symptoms in May 2020 related to a T4/T5 mass. Clinical features included bone pain, recurrent infection, spinal cord compression, and peripheral neuropathy. He underwent laminectomy and tumor debulking in June 2020, during which a biopsy of his lesion was taken that revealed a plasmacytoma. Bone marrow biopsy showed no definitive evidence of a monoclonal plasma cell population, but the patient met the criteria for multiple myeloma (plasmacytoma and lytic lesions) and was started on multiple chemotherapeutic agents. After developing pancytopenia and fever post-chemotherapy, he developed septic shock that manifested as lactic acidosis, disseminated intravascular coagulation (DIC), renal failure, and elevated transaminases. He was transferred to the ICU. Blood and scrotal wound cultures were sent that grew Pseudomonas aeroginosa. He was intubated and required multiple vasopressors and broad-spectrum antibiotics. Methylene blue was also used to elevate his blood pressure approximately 27 hours prior to death. Due to the poor prognosis, the family chose to pursue comfort care measures only, and the patient expired shortly thereafter due to septic shock.
An unrestricted autopsy was requested by the family and treating clinicians. The post-mortem examination revealed a full-thickness scrotal ulcer, and an edematous, hemorrhagic left testicle. Gross findings also included superficial sacral decubitus ulcers, severe calcific coronary, and systemic atherosclerotic cardiovascular disease, cardiomegaly, pulmonary edema, bilateral pleural effusions, and thromboemboli entangled in the IVC filter (Figure , ). Histologic findings included areas of hemorrhagic necrosis and bacterial overgrowth in the scrotal ulcer sections, hemorrhage (Figure ) and congestion (Figure ) in the left testicle, and nodular glomerulosclerosis.
The unique finding was bluish-green discoloration of organs including the brain (Figure ), heart (Figure , ), lungs, and kidneys during autopsy, which was secondary to methylene blue treatment in this patient of septic shock due to Pseudomonas aeroginosa bacteremia secondary to acute folliculitis and epididymo-orchitis (perforated/ulcerated scrotum with areas of hemorrhagic necrosis) (Figure ). This discoloration increased from green to turquoise blue as the organs were set on the table for dissection.


The patient was a 3-year-old boy, who suffered from recurrent seizures for 2 years and 8 months and suffered from recurrent vomiting for 1 year and 7 months. At the age of 3 months, he was found to be blind. At 3 months and 20 days old, he showed a series of seizures during his awakening period. These seizures consisted of nodding, clasping, and squinting to the right, with 2–3 strings a day, 7–8 times a string, and 7–8 strings a day at most. VEEG (video electroencephalogram) result showed highly dysrhythmic brain waves and caught two tonic–clonic seizures. Brain MRI showed no obvious abnormality. Since then, he received antiepileptic treatment. Sodium valproate was ineffective, treatment was switched to topiramate, and the dosage was gradually increased. At 6 months old, he had no obvious seizures but still had mental retardation.
At the age of 1 year and four months, he began to vomit frequently, accompanied by adduction flexion of both upper limbs, trembling of limbs, gaze, and cyanosis around the mouth, which lasted for about half an hour. Because of recurrent vomiting accompanied by focal seizures, he was frequently admitted to the hospital, and each hospitalization examination showed obvious blood acidosis. Urine screening showed hyperlactic acidemia with increased ketonuria, glycosuria, and several organic acids. Blood screening showed that Ala, Phe/Tyr, CO, C2, C3, and C4-OH increased and Gly, Leu/Ile, Trp, Thr, Val, Gly/Ala, and Val/Phe decreased. After that, the patient developed heavy breathing symptoms, exhibited during sleep. Electrolyte levels were checked in the hospital, and CO2 was found to be 12.3 mmol/L. After the symptomatic treatment of energy, levocarnitine, ambroxol, and so on, he was discharged after improvement. After discharge, the child still had frequent epileptic seizures for a period of time and continued to take topiramate 25 mg q12h orally. Hematuria metabolic screening, mutation screening of mitochondrial gene, and mitochondrial nuclear gene were negative. The respiratory chain enzyme activity of the exceptional blood was normal. At the age of one year and four months, VEEG showed abnormal EEG: highly irregular electroencephalogram, slow background activity, and paroxysmal δ activity in bilateral frontal and occipital regions during sleep. Brain MRI showed an abnormal signal in the left pontine arm, thickening of the cerebral cortex, decrease in the medulla, enlargement of the ventricles, widening of the sulci and fissures, and increase in DWI signal in subcortical white matter.
The patient was the third child, the third delivery, full-term labor, and spontaneous delivery. There was no history of umbilical cord around the neck and postnatal asphyxia. The birthweight was 2.6 kg and healthy in the neonatal period. At present, the patient cannot sit, stand, or walk. The father of the patient was healthy. The mother complained of folic acid deficiency but no clinical manifestations, and recovered after folic acid supplementation. She supplemented folic acid constantly both before and after pregnancy. The folic acid test of the patient was normal. One of his elder sister (G1P1) had almost the same symptoms as him: developmental retardation, epilepsy, recurrent vomiting, strabismus but not blindness, and so on. She died of seizures at the age of 3. Another elder sister (G2P2) was healthy and did not have the genetic detection. His younger brother had a genetic examination on amniotic fluid before delivery after the patient's gene was confirmed. The results showed that his GFM1 gene carried heterozygous c.1765-2-1765-1delAG and did not carry c.679G > A (p.G227R) mutation (Figure ). The study protocol was approved by the ethical committee of Linyi People's Hospital Affiliated to Shandong University (No.13003). The parents signed informed consent forms.
Total DNA from peripheral blood leukocytes of the patient and his parents was extracted using the Genomic DNA Extraction Kit (Sangon Biotech) and stored at −20°C prior to use. Gene capture and high-throughput screening were performed using whole-exome sequencing (MyGenostics).
Software CASAVA (v1.8.2) was used for base calling of original image data of sequencing results. Short read mapping and alignment with human reference genome (hg19) were performed using BWA software (version 0.7.12, RRID: SCR_010910) (Li & Durbin, ). SNV/InDel identification was carried out by using SAMTOOLS software (Li et al., ), and the specific sequencing information of each site was analyzed by SAMTOOLS Mpileup module and Bcftools. The detected mutation sites were annotated by ANNOVAR software (RRID: SCR_012821) (Wang, Li, & Hakonarson, ). At the same time, we detected the gene package of mitochondrial disease in the patient and his family, and the results were consistent with the sequencing of high-throughput exons.


A 67 year-old male living in tropical northern Australia presented with left sided abdominal pain, fever and pyuria. Computed tomography (CT) demonstrated abnormal enhancement of the lower pole of his left kidney, thickened pelvic urothelium and perinephric fat stranding. A provisional diagnosis of pyelonephritis was made, and he was empirically treated with intravenous ampicillin and gentamicin. His past medical history was significant for recurrent sinusitis with eosinophilia and positive perinuclear antineutrophil cytoplasmic antibodies, and he was on treatment for eosinophilic granulomatosis with polyangiitis (EGPA) with mycophenolate mofetil 750 mg twice daily and prednisone 5 mg daily.
Urine microscopy showed > 100 × 106 leucocytes/L, but no pathogen was isolated. Despite antibiotic therapy he had ongoing fevers and persistent flank pain. On day five, he developed an erythematous, indurated lesion on his left upper thigh, and the following day a similar lesion developed on his anterior abdominal wall, with the appearance of ischemic panniculitis (Fig. ). A repeat CT scan on day 6 demonstrated absent perfusion in the lower pole of the left kidney, consistent with infarction (Fig. ). A skin lesion biopsy was performed 2 days later, and he was commenced on methylprednisolone as treatment for presumed vasculitis. Twenty-four hours later, culture of the skin biopsy demonstrated growth of a fungus with the appearance of an organism of the order Mucorales on Sabouraud dextrose agar at 30° and 37 °C. He was commenced on intravenous (IV) liposomal amphotericin B 8 mg/kg daily for treatment of presumed disseminated mucormycosis, and both skin lesions were extensively debrided. Intraoperatively, panniculitis with necrosis was found to extend to the deep fascia. Histologic examination showed fungal hyphae with angioinvasion and infarction of subcutaneous tissue (Fig. a). In light of this, all immunosuppression was ceased. Four days later the patient underwent a left nephrectomy, and histologic examination of the kidney revealed necrosis with aseptate, branching hyphae consistent with organisms of the order Mucorales (Fig. b).
Fungal microscopy with calcofluor staining following 10% potassium hydroxide (KOH) digestion of renal tissue confirmed the presence of wide ribbon-like aseptate fungal hyphae consistent with zygomycete infection. Tissue was cultured on Sabouraud’s dextrose agar which grew a white cottony fungus at 30, 37 and 40 °C on day 3. The isolate was referred to the National Mycology Reference Centre, where the fungus was identified as Saksenaea species (sp.) via sequencing of the internal transcribed spacer (ITS1–5.8S-ITS2) region of the ribosomal deoxyribonucleic acid (DNA) and Nucleotide Basic Local Alignment Search Tool (BLASTn) comparison to publicly accessible sequence databases. This demonstrated 93 and 91% sequence similarity to S. trapezispora and S. oblongispora Type material, respectively, in both the National Center for Biotechnology Information (NCBI) database () and the Westerdijk Fungal Biodiversity Institute database () [], and 81% similarity to S. vasiformis using the International Society of Human and Animal Mycology (ISHAM) barcoding database (). This was considered insufficient for definitive species identification. Further investigation of the species identification, including the possibility of a novel species, will be conducted. The isolate failed to sporulate after 6 weeks of incubation, despite the use of a range of sporulation-inducing media including Potato Dextrose agar and Tap Water agar at 25 °C and 35 °C; therefore antifungal susceptibility testing could not be performed. The patient received 6 weeks of IV amphotericin; oral posaconazole was added 3 weeks into therapy, though significant improvement had been observed following surgical intervention. Posaconazole was given in the form of delayed release tablets 300 mg, with a 12-h interval between the first two doses and daily dosing thereafter. His treatment course was complicated by acute kidney injury likely secondary to IV liposomal amphotericin requiring dose reduction, and abnormal liver function tests likely secondary to posaconazole. He was discharged home after 57 days in hospital on oral posaconazole treatment. Therapeutic drug monitoring of posaconazole was performed and levels were considered therapeutic between 1.5 and 3.3 mg/L.
Three months following discharge, he represented with dyspnoea, rhinorrhoea and cough. CT demonstrated consolidation in the lower lobe of the left lung and upper lobe opacities with inflammatory change in the sinuses. Bronchoscopy was unremarkable and fungal culture was negative. This presentation was thought to be secondary to a flare of eosinophilic granulomatosis with polyangiitis in the setting of cessation of his immunosuppression. He received prednisone, which was slowly weaned, and was later switched to mepolizumab (an interleukin-5 inhibitor) for ongoing treatment of EGPA. The patient has received 18 months of posaconazole treatment with no evidence of recurrence of infection, and we remain cautiously optimistic.


A 38-year-old man, who was deprived of his liberty at prison for several years until three months before his admission, arrived at another institution for ecchymotic lesions, productive cough, weight loss, anorexia, epistaxis, and low-grade fever of 20-day duration, without previous trauma. His past medical history was otherwise unremarkable, and he reported not having previous alterations in clinical and laboratory examinations whatsoever. Laboratory tests at admission were as follows: leukocytes 9,460/mL (NR: 4,230 - 9,070), neutrophils 82% (NR: 34-67.9), hemoglobin 10.4 g/dL (NR: 13.7-17.5) hematocrit 30 mg/dL (NR: 40.1-51), erythrocyte sedimentation rate 83.3 mm/h (NR: 0-15), platelets 5000/mL (NR: 163 000-337 000), PT 11.8 (control: 11.3), PTT 29 (control: 30.9), Fibrinogen 509 mg/dL (NR: 150-400), D-dimer 13 080 μg/mL (NR: 0-0.5), total bilirubin 0.95 (NR: 0-1.2), lactic dehydrogenase (LDH) 206 IU/L (NR: 135 - 225), alkaline phosphatase 80 IU/L (NR: 20-140), folic acid 11.49 ng/mL (2.6-17), and vitamin B12 357 ng/mL (NR: 197-771). He had negative ELISA for HIV, negative hepatitis B surface antigen, and hepatitis C antibody; nonreactive RPR, direct bacilloscopy was negative; urinalysis had macroscopic hematuria; and urine culture was negative. A chest X-ray showed a cavitating lung lesion with thick edges in the left pulmonary apex (Figure ). The case was interpreted as an idiopathic thrombocytopenic purpura, and due to platelet count, intravenous (IV) immunoglobulin G was started, along with methylprednisolone 1 mg/kg/day. Ivermectin 70 drops single dose and Albendazole 400 mg/d for 3 days were initiated before immune therapy, in order to prevent opportunistic helminthic infections.
On his fourth day of hospitalization, he developed hemodynamic instability, given by persistence of active bleeding: hematemesis, epistaxis, hematuria, and severe secondary anemia, requiring blood transfusion and apheresis platelets. He was referred to our institution in poor general conditions. On physical examination: blood pressure 110/70 mm Hg, heart rate 75 bpm, respiratory rate 13 bpm, oral cavity with petechial lesions, coarse crackles in both lungs, multiple petechiae, and ecchymoses spread all along the extremities. The rest of the physical examination was unremarkable. Laboratory tests showed leukocytes 11 200/μL, neutrophils 10 240/μL, lymphocytes 530/μL, hemoglobin 9.8 g/dL, hematocrit 28%, platelets 1000/μL, PT 15, INR 1.38, PTT 27.5, Fibrinogen 738, total bilirubin 0.95, ALT 12 mg/dL (NR: 0-41), AST 28 mg/dL (NR: 0-38), LDH 397 IU/L, IgA: 1.88 (NR: 0.7-4.0), IgG: 33 (NR: 7-16), and IgM: 1.17 (NR: 0.4-2.3). HIV antibodies were negative, and viral load was undetectable. Chest X-ray showed a thick-walled cavitating image in the left pulmonary apex with effacement of the left costophrenic angle probably due to effusion or pleural thickening. A thoracic CT scan showed a left apical cavity with irregular borders and hydro-aerial level, with nodules of inflammatory aspect, ipsilateral endobronchial dissemination, and left pleural effusion (Figure B-D). Bacilloscopy was positive in urine. Bone marrow aspirate and biopsy were negative for neoplastic infiltration. A fibrobronchoscopy plus bronchoalveolar lavage (BAL) was performed, showing generalized severe endobronchial inflammation without obstruction or masses. BAL showed inflammatory cells in cytology study, macrophages, and plentiful lymphocytes with no evidence of malignancy. Ziehl-Neelsen stain was positive +++, and galactomannan was negative. GeneXpert was positive without evidence of antibiotic resistance. The aforementioned test is a rapid, simple-to-use nucleic acid amplification test, which detects DNA sequences specific for M. tuberculosis and rifampicin resistance using polymerase chain reaction.
Supervised shortened oral anti-TB treatment was initiated on a weight-based dosing, as follows: rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, ethambutol 275 mg four tablets, and pyridoxine 50mg daily. Due to thrombocytopenia and evident hemorrhagic manifestations, he required multiple blood transfusions and apheresis of platelets. Following the findings in the bone marrow in which there was no neoplastic or lymphoproliferative infiltration, a diagnosis of ITP was made in the context of active tuberculosis. Concomitant treatment with dexamethasone 40 mg/d for 4 days and immunoglobulin G 50 g/d for 2 days was initiated.
The patient improved his general condition one week after starting the therapeutic scheme, without new bleeding episodes and improvement of laboratory tests: leukocytes 5190/μL, neutrophils 3160/μL, lymphocytes 1170/μL, hemoglobin 10.6, hematocrit 30.8%, platelets 53 000/μL, creatinine 0.77 (NR: 0.67-1.17), ALT 64.4, AST 73.2, sodium 132 mmol/L (NR: 136-145), potassium 4.49 mmol/L (NR: 3.5-5.1); chloride 98 mmol/L (NR: 98-107), magnesium 2.19 mmol/L (NR: 1.59-2.56), and phosphorus 3.34 mmol/L (NR: 2.5-4.5).
The patient continued steroid therapy with oral prednisolone 1 mg/kg with a gradual dose decrease in the following month as well as supervised shortened TB treatment for six months, without adverse effects or recurrence of ITP.


A 24-year-old Caucasian woman with a past medical history significant for congenital BWS presented with vague abdominal pain that waxed and waned in intensity beginning in August 2018. The patient had clinical manifestations of BWS at birth with characteristic umbilical hernia, macroglossia, and hemihypertrophy of her right lower extremity. Genetic analysis confirmed the diagnosis of BWS in January 2011 with uniparental disomy of the chromosome 11 region, hypermethylation of the H19DMR (IC1) loci, and hypomethylation of the KvDMR (IC2) loci. In addition to diagnosis of BWS, the patient's past medical history was significant for partial pancreatectomy due to pancreatic cystic lesions, left mastectomy, and several right-sided lumpectomies due to breast fibroadenomas, refractory immune thrombocytopenic purpura requiring splenectomy, and systemic lupus erythematosus.
In May 2019, she was found on CT chest, abdomen, and pelvis to have interval development of parenchymal heterogeneity and multiple enhancing nodules and masses in the liver measuring up to 3.6 cm in the right dome (). Two months later on MRI, the patient was found to have a 3 cm lesion in the right hepatic dome of the liver (). Tumor and autoimmune laboratory markers at this time demonstrated a normal alpha fetoprotein at 2.7, a mildly elevated carcinoembryonic antigen at 3.8, an elevated carbohydrate antigen 19–9 at 136, a positive antinuclear antibody 1:1280, and a positive smooth muscle (F-actin) immunoglobin G. Ceruloplasmin, antimitochondrial antibody, alpha-1-antitrypsin, and viral hepatitis serologies were negative. Liver function was preserved, but a marker of liver inflammation, aspartate aminotransferase, was mildly elevated to 65. Alanine aminotransferase was normal at 39, and the patient's alkaline phosphatase was elevated to 211.
Given the above imaging and laboratory results, an ultrasound-guided liver biopsy was performed by interventional radiology in October 2019. The biopsy was described as a hepatocellular proliferation with thickened cell plates and pseudoglands (). No portal tracts were observed, but some unpaired arteries were noted. A low-grade, well-differentiated hepatocellular neoplasm was diagnosed due to the frequent pseudoglandular formations and the thickened cell plates. At this time, the patient denied other symptoms, including fever, chills, nausea, vomiting, weight loss, headache, dyspnea, flank pain, constipation, diarrhea, melena, hematochezia, focal weakness, or back pain. Right posterior sectionectomy of the liver was performed in December 2019.
Serial sections of the surgical specimen revealed a 2.9 × 2.8 × 2.0 cm tan, soft, and hemorrhagic mass with irregular borders. Histological examination demonstrated similar findings to those seen in the biopsy, with diffusely thickened cell plates and pseudoglands (Figures and ). The reticulin stain confirmed the presence of thickened cell plates (). The tumor was extensively sampled, and no areas were concerning for embryonal or fetal differentiation, which would have been suggestive of hepatoblastoma. The background of the liver showed mass-effect changes and focal perisinusoidal fibrosis. The surgical specimen confirmed the diagnosis of low-grade, well-differentiated hepatocellular carcinoma. The patient was discharged home a week later. Written informed consent was obtained from the patient for this case report.


The patient was a 53-year-old right-handed female who presented an unknown onset seizure with motor activity (tonic- clonic) at the age of 17 years. Personal history for other neurological conditions was negative. Epilepsy risk factors, including febrile seizures, head trauma, central nervous system (CNS) tumor, and family history, were also negative. The patient denied smoking, drinking alcohol, or using illicit drugs. The neurological exam was normal, and she scored 26/30 on the Montreal Cognitive Assessment (MOCA) test. Interestingly, she did not have more seizures until she was 26 years old. This last seizure had a focal onset, with impaired awareness, and a motor component that involved manual automatism, blinking, cephalic version to the right, and asymmetric tonic limb posturing with progression to bilateral tonic-clonic seizures.
Her seizures worsened progressively due to increased frequency and severity, with an ictal frequency of five per month. She was on carbamazepine 400 mg daily, levetiracetam 3000 mg daily, lacosamide 250 mg daily, and lamotrogine 100 mg daily with poor response. Then, she was referred to our hospital (Hospital Universitario Mayor—Méderi) to characterize her seizures. A long-term (72 h) video EEG with scalp electrodes was performed with a 50% reduction of the antiepileptic drug (AED) doses. The video EEG recorded 14 seizures in total. She presented two different types of seizures with different semiology: the first type was a seizure with a focal onset, impaired awareness, and non-motor components such as behavior arrest, cognitive impairment due to disorientation and emotional seizures (psychomotor agitation, fear, and anxiety) and eye blinking. The second one was a focal onset seizure with impaired awareness, motor components such as eye blinking, cephalic version to the right, dystonic extension posture in the right arm (Figure 4 sign), and finally a progression to bilateral tonic-clonic seizure. After video EEG was completed, she was restarted on the full dose of AEDs, achieving seizure control within the next 24 h.
The scalp EEG showed interictal rhythmic spike activity in the left mesial temporal region maximal at the T3 electrode. A Left F7-T3 spike with intermittent fronto-central delta slowing was found. A right interictal temporal spike was also seen at the end of the recording (). Ictal scalp EEG showed 4–5 Hz rhythmic activity that involved the right frontotemporal region. It spread to the contralateral hemisphere, where it was associated with epileptiform activity ( and ).
A computed tomography (CT) scan showed a left frontal parasagittal lesion with calcifications without mass effect. Then, a 1.5 Tesla brain magnetic resonance image (MRI) was obtained and confirmed the presence of a 9 × 6 mm left frontal parasagittal lesion with the so-called ‘popcorn’ appearance. The nodule showed smooth, thin, and hypointense borders, with a homogeneously hyperintense core on the T2W (weighted) images. The T2 gradient echo (GRE) images defined the hemosiderin component of the lesion, also known as ‘the blooming effect’. It did not enhance on T1W post-gadolinium images (). Positron emission tomography (PET) brain imaging using [18] FDG fluorodeoxyglucose showed a pseudonodular lesion with internal calcifications of 9 × 6 mm approximately without radiopharmaceutical uptake (ametabolic). No abnormal perfusion in the surrounding area next to the cavernoma was found. An acceptable distribution and radiofrequency uptake by other brain structures, including the temporal lobes, was shown ().
In summary, the present case characterized by ictal semiology and onset in the left hemisphere matched to the side of the cavernoma localization. However, the scalp EEG showed a right onset and fast spread to the contralateral hemisphere, meaning there was conflicting evidence regarding lateralization.
According to several guidelines for cavernoma-related epilepsy management [,], surgical resection of the cavernoma was offered to the patient by our epilepsy group. However, the patient declined the procedure for personal reasons, and AED therapy was restarted. Medication dosage was adjusted (levetiracetam 2000 mg daily and lamotrigine 400 mg daily) due to the development of somnolence and drowsiness, resulting in partial control of the seizures.


Our patient is a 24-year-old black male, who presented to us for the evaluation of persistent abdominal pain, diarrhea, and weight loss. He describes a six-month history of episodic, diffuse, and crampy abdominal pain. Each episode would last about five to ten minutes and was mild to moderate in intensity. The pain would resolve spontaneously, and there were no associated symptoms, aggravating, or alleviating factors. Three months prior to his presentation, he started experiencing loose, watery diarrhea which would occur every two to three days. He described having three to four loose bowel movements per day, with no presence of mucus or blood. He also complained of anorexia and a 10 lb weight loss over the previous three months.
A comprehensive review of systems was otherwise negative. He denied any fever, chills, or any relation of his diarrhea to food intake, and there was no history of nocturnal diarrhea. There was no recent antibiotic use and no history of recent travel or sick contacts. He denies any joint pain, skin rash, or mouth ulcers. There was no history of shortness of breath, cough, wheezing, chest pain, or urinary symptoms.
His past medical history was significant for Lyme disease in childhood and attention-deficit hyperactive disorder. There was no history of surgery in the past. He denied any history of smoking, alcohol use, or recreational drug use. There was no family history of inflammatory bowel disease (IBD), colon cancer, or any other GI malignancies.
On physical examination, the patient appeared malnourished, evident by temporal wasting. His vital signs were generally unremarkable. He weighed 134 lb (60.8 kg) which puts him at a BMI of 17.80 kg/m2. Examination of the gastrointestinal system was unremarkable, with a soft, nontender abdomen, with no visceromegaly. There was no scleral icterus or conjunctival pallor. The remainder of the physical exam was normal.
Results of routine hematology and biochemistry investigations including liver enzymes were all within normal limits. Celiac serology was negative, and stool workup including fecal leukocytes, stool culture, ova and parasites, giardia, and cryptosporidium were all negative. His carcinoembryonic antigen (CEA) was within normal limits.
Colonoscopy showed a circumferentially encasing, partially obstructing, stenotic mass, with overlying granular and inflammatory mucosa in the hepatic flexure (Figures –). The colonoscope could not be negotiated through the mass to evaluate the cecum. The colonic biopsy revealed soft consistency of the mass, and there was excess of bleeding from the biopsy site (). The colonic mucosa of the remaining part of the colon appeared normal, and random colon biopsy was obtained. The histopathology of the hepatic flexure mass was significant for focal active chronic colitis with ulceration, polypoid granulation tissue formation, reactive epithelial changes, and noncaseating granulomata formation that was consistent with granulomatous inflammation (). Special stains for tuberculosis, fungi, and other microorganisms were all negative. The crypt architecture was preserved (), and the histopathological findings were devoid of the basal cell plasmacytosis to conclude to inflammatory bowel disease. Esophagogastroduodenoscopy was performed and was unremarkable; biopsies of gastric and duodenal tissues and subsequent testing for Helicobacter pylori infection, celiac disease, and Whipple disease were all negative.
An abdominal CT scan of the abdomen performed with contrast was remarkable for circumferential thickening of the cecum and ascending colon without any evidence of obstruction. There were perihepatic and pelvic ascites in the cul-de-sac and nodular thickening of the peritoneum in the right lateral abdominal wall and minimally at the omentum. The patient subsequently underwent a laparoscopic peritoneal biopsy. The biopsy specimen showed noncaseating granulomas and confluent granulomatous inflammation. Special stains for tuberculosis and fungi were negative.
A CT scan of the chest was performed and revealed a slightly irregular 1 cm pulmonary nodule in the superior segment of the right lower lobe. The area of nodular sarcoid cannot be excluded. There was also minimal fissural nodularity which could represent underlying sarcoid.
A diagnosis of colonic sarcoidosis was made, and the patient was treated medically with oral prednisone, starting at 40 mg daily for one week with a gradual taper to a target maintenance dose of 5 mg daily over the course of eight weeks. Upon starting prednisone, the patient improved clinically with the resolution of his abdominal pain and diarrhea, along with a 20 lb weight gain, and remained in sustained symptomatic remission after three months of treatment. A colonoscopy performed five months after treatment revealed interval improvement of colonic stenosis resolution of the inflammatory mass, and the scope could be traversed through the stricture (). Some mucosal inflammation and granularity could be noted; however, there was significant improvement as compared to the index colonoscopy (). The biopsy specimens from the previously involved areas showed chronic mucosal injury with no evidence of dysplasia, malignancy, or noncaseating granulomas ().


A 77-year-old Caucasian man with a history of Hodgkin’s lymphoma treated with thymectomy and radiation at the age of 28 presented to the hospital with a chief complaint of a painless mass in his left breast of a few days’ duration. His other comorbidities included atrial fibrillation on anticoagulation, obstructive sleep apnea, and a remote history of pulmonary embolism. He denied any known family history of breast or other types of cancer.
On examination of the left breast, the area was non-erythematous with a palpable 1.5 cm firm, circular, painless mass in the left lower quadrant, subareolar region. The patient had a mammogram showing a 1.8 cm x 1.8 cm x 1.5 cm left subareolar lobulated mass highly suggestive of malignancy (BIRADS 5) (Figure ). Left breast ultrasound showed a hypoechoic vascular mass with microlobular margins of similar size (Figure ). Left axillary lymph nodes and right breast appeared normal at the time of imaging. A positron emission tomography (PET) scan for initial cancer screening was performed with no signs of nodal or distant metastasis. Needle core biopsy of the mass was performed and showed infiltrating ductal carcinoma (IDC) Grade 1 (mitotic rate: score 1, pleomorphism: score 2, tubules: score 3, total score: 5) (Figure ). Immunohistochemical results were estrogen receptor (ER) positive (>90%), progesterone receptor (PR) positive (>90%), HER2/Neu 2+ equivocal with no amplification on fluorescence in situ hybrid (FISH), and E-Cadherin positive within tumor cells. The patient tested negative for mutations in the genes BRCA 1 and 2, TP53, PTEN, and PALB2.
The patient underwent a left modified radical mastectomy and a 1.7 x 1.5 cm solid, pale pink, well circumscribed mass was found subjacent to the nipple with a 0.4 cm central area of hemorrhage. Eight lymph nodes were dissected with one positive for metastatic carcinoma with three metastatic foci in the node. The largest focus measured 0.3 cm and was HER2 negative. Microscopic evaluation determined the patient to have invasive micropapillary carcinoma of the left breast and pathologic staging was evaluated at PT1c N1a Mx. Oncotype DX for breast recurrence was four, distance recurrence risk at nine years at 3%, and no apparent benefit of chemotherapy. After discussing the treatment options at length, the patient opted for surveillance with annual mammograms and no adjuvant chemotherapy, hormonal therapy, or radiation therapy.


A 50-year-old female patient was admitted with a 7-week history of postural headache deteriorating in upright position accompanied by nausea and vomiting. At neurological examination, she presented without any pathological findings, especially no symptoms of lumbar nerve root compression. The medical history of the athletic patient revealed no relevant previous disease or trauma.


A 19-year-old male collegiate athlete with no chronic illnesses presented to the Emergency Department with typical anginal symptoms after running a 5K race. He had chest tightness and sharp pain localized to his center and left chest. Associated symptoms included mild back pain and left arm tingling. He had similar symptoms for the month prior to presentation, which he would experience 15-20 minutes following a strenuous workout and lasting up to 2 hours. He presented to the hospital after his race because his pain was persistent and unremitting through the day.
His family history includes hypertension and type 2 diabetes mellitus in his parents. The patient denied history of tobacco, alcohol, or illicit drug use including cannabis and cocaine.
On arrival to the hospital, vital signs were stable with blood pressure 143/87 mmHg and heart rate of 81 beats per minute. Physical exam was unremarkable. The patient's ECG showed diffuse ST-segment changes and T-wave inversions. Troponin was 0.12 ng/ml on presentation and peaked at 17.7 ng/ml. CK-MB was 28.1 IU/L.
The patient was given aspirin, morphine, and metoprolol and admitted for workup and treatment of NSTEMI.


A 32-year-old man who had been diagnosed with Crohn disease 7 years previously was admitted to our hospital with TB. Since diagnosis, his Crohn disease had been managed with infliximab. Before starting infliximab, he had tested negative for M. tuberculosis using an interferon-γ release assay. He visited a clinic complaining of persistent fever and cough that had started one week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. A computed tomography (CT) scan of his chest revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of M. tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB and was started on antituberculous therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol). Six days after starting antituberculous therapy, he was transferred to the University of the Ryukyus Hospital in Okinawa, Japan, for further management.
The patient's clinical course and chest X-ray findings are shown in Figure . His symptoms initially improved after starting antituberculous therapy, but his high fever recurred within 2 weeks of starting treatment, and his cough recurred within 3 weeks. Initially, his fever was thought to be a reaction to the antituberculous drugs, so his TB treatment regimen was changed to a combination of streptomycin, ethionamide, and levofloxacin on Day 15. However, his clinical condition continued to deteriorate. A repeat chest CT scan, done on Day 23, revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion (Fig. ). This paradoxical exacerbation was diagnosed as anti-TNFα-induced TB-IRIS, associated with infliximab, and a systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)] on Day 24. After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. He was discharged on Day 41.
After discharge, the M. tuberculosis strain that had been cultured from a sputum sample was found to be fully susceptible to the antituberculous drugs that were being administered. Prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. Infliximab was withdrawn at the initiation of antituberculous therapy and had not been restarted at the time of his most recent follow-up, 14 months after his discharge.
The patient provided written informed consent for his case history, and chest X-ray and CT scans to be published (University of the Ryukyus Hospitals consent form).


A 49-year-old woman hospitalized at the Department of Plastic and Maxillofacial Surgery, presented with a growing mass in her left maxillary hard palate dating 2 months back. She was diagnosed with an oral ulcer at a local clinic, and received antibiotics. However, the symptoms did not improve; the mass became bigger and painful. Her past medical history was unremarkable without any systemic disease. No obvious physical findings were noted during general examination. She had no bouts of fever, chills, night sweats, vomiting, or weight loss. The intraoral examination revealed that there was a mass measuring 3.0 cm × 2.0 cm in size, with ulcerated surface mucosa in the left maxillary hard palate (Fig. ).
To obtain a definitive diagnosis, an incisional biopsy of the oral mass was performed under local anesthesia. Histologic examination using hematoxylin and eosin staining revealed that there was diffuse cell infiltration growth. Most cells were large, with vacuolated nuclei, obvious nucleoli and a basophilic cytoplasm containing granules (Fig. ). For the final diagnosis, immunohistochemistry (IHC) was performed, and the tumor cells tested positive for MPO, CD4, BCL-2, KI-67 (Fig. ), and CD117 and negative for CD3, CD5, CD20, CD56, bcl-6, Mum-1, CD123, MUM-1, TdT, Syn, SOX11, and C-myc. These results supported the diagnosis of GS.
The patient was then referred to the Hematology Department. Bone marrow aspiration was negative for malignant cells, and the laboratory test results revealed only monocytosis. Standard bone marrow cytogenetic analysis showed a normal karyotype and leukemia-related fusion gene detection was normal. Therefore, according to IHC and bone marrow aspiration results in combination with morphological features, the final diagnosis was intraoral primary GS.
A chemotherapy regimen comprising idarubicin 8 mg VD d1–3 and cytarabine arabinoside 150 mg VD d1–7 idarubicin and cytarabine arabinoside was initiated. During chemotherapy, the patient only appeared mild nausea, vomiting and canker sores (grade II). These symptoms gradually eased without special therapy. After 2 cycles of idarubicin and cytarabine arabinoside regimen chemotherapy, the patient achieved complete remission. The tumor was barely visible in the left maxillary hard palate (Fig. ). The patient denied consolidation therapy or bone marrow transplant. Nevertheless, there has been no evidence of disease spread and progression after 1 year of follow-up.


A 60-year-old woman presented with dyspnea and cough. She had a history of Stage IB squamous cell cervical carcinoma in 2005, treated with surgery and adjuvant radiotherapy, and brachytherapy. Chest and abdominal computed tomography (CT) scans and fludeoxyglucose (18F) positron emission-computed tomography (PET-CT) showed mediastinal metastases without lung, pelvic, or abdominal disease. Mediastinal biopsy by mediastinoscopy confirmed metastatic disease from squamous cell carcinoma. She was evaluated by thoracic surgeons who considered her metastases to be unresectable due to compromise of the superior vena cava, azygos vein, and right main bronchus. Therefore, she was treated with mediastinal intensity-modulated radiotherapy (IMRT) 60 Gy at 2.0 Gy per fraction, concurrent with weekly intravenous cisplatin 40 mg/m2 per week, for six weeks. This treatment was done between April and May 2016. Post-treatment chest CT showed a partial response, with only one right parahilar lymphadenopathy persisting. After this, a control PET-CT reported residual-appearing lymphadenopathy, with a reduction in its hypermetabolism (Figure ). Subsequently, successive PET-CT showed progressive decrease in metabolism until its total resolution at the time of her last visit at our hospital in July 2019. She remained alive and free of tumor relapse or progression (Figure ) as of June 2020.


A 57-year-old woman with a medical history of cervical adenocarcinoma in 2013 treated with concurrent pelvic IMRT and weekly cisplatin for six doses, followed by brachytherapy, with complete response presented in 2016 with biochemical recurrence with elevated cancer antigen 125 (CA-125) of 67.65 U/mL (reference range, 0.0 to 35 U/mL). Her CT showed metastatic relapse with mediastinal lymphadenopathies (Station 2L, pretracheal, and aortopulmonary window; Figure ). She did six cycles of chemotherapy with carboplatin and paclitaxel for six cycles, with stable disease. Then, she received thoracic IMRT at 60 Gy in 2-Gy fractions, concurrent with cisplatin 40 mg/m2 weekly for six weeks, from May to June 2017. After this, she had normalization of tumor marker and a progressive decrease in size and metabolism of the lesions until she reached complete response (Figure , ). In her last follow-up visit in March 2020, her CA-125 levels were within the reference range. Table presents her biochemical profile.


A 68-year-old woman with a past medical history of hypertension with prior hysterectomy presented with acute pain over her right groin. On arrival to the emergency room, her vital signs were stable, and clinical examination was remarkable only for pain and tenderness at the right groin on palpation. Her blood work was significant for leukocytosis of 20x103 WBC/mL. A computed tomography (CT) of the abdomen and pelvis revealed an incarcerated right femoral hernia with an inflamed appendix as its contents (Figure ).
She underwent laparoscopic exploration where an inflamed appendix entering the femoral hernia sac was found intraoperatively (Figure ).
After reducing the appendix, an appendectomy was done, with thorough saline irrigation of the dependent areas. The hernial sac was reduced, and no mesh was placed. The postoperative course was uneventful as the patient tolerated a regular diet on postoperative day one and was discharged home. Three months follow up, the patient did not have a symptomatic inguinal hernia.


A 56-year-old male with a past medical history significant for non-insulin-dependent diabetes mellitus presented with a painful right groin bulge. On arrival to the emergency room, the patient had sinus tachycardia with a heart rate of a 110 bpm. Physical examination was remarkable for pain and tenderness to palpation on right inguinal hernia. Blood work revealed leukocytosis of 21x10^3/mL. A CT scan of the abdomen and pelvis showed an incarcerated right groin hernia with an inflamed appendix as one of its contents (Figure ).
The patient was taken emergently for laparoscopic surgery which revealed an inflamed and purulent appendix (Figure ).
Since it was not possible to proceed with the reduction of the hernial sac laparoscopically in view of severe inflammation, conversion to open surgery occurred. First, the inflamed contents were mobilized laparoscopically and brought out via a small midline incision using a wound protector device. Second, an ileocolectomy and a side-to-side anastomosis was performed extracorporeally. Third, the contents were subsequently reduced back into the abdomen with the closure of the fascia using running polydioxanone (PDS) sutures. The postoperative course was complicated by a scrotal abscess that requiring drainage. The patient was discharged home on postoperative day seven with a one-week course of cephalosporin for Escherichia coli growth in wound. Three months follow up time was significant for no visible hernia.


A 45-year-old male patient with no past medical history presented with an acutely painful umbilical bulge. On arrival to the emergency room, his vital signs were stable and physical examination was positive for a very tender and erythematous bulge at the umbilicus consistent with an incarcerated hernia. Blood work was remarkable for leukocytosis to 11x10^3/mL. The patient was emergently taken for diagnostic laparoscopy and an inflamed appendix was seen incarcerated into the umbilical hernia (Figure ).
An appendectomy was performed with saline irrigation of the pelvis and paracolic gutters after which no pockets of pus were seen. Primary repair of the hernial sac was performed with absorbable polyglactin sutures and the patient was discharged on postoperative day three. No visible hernia was seen on three months follow-up.


We presented the case of a 5-year-1-month-old boy who was referred to our outpatient clinic when he was 4-year-10-month-old (timeline of clinical course—Fig. illustrates the clinical course).
The patient was examined because of prolonged unresolved pretibial haematoma (Fig. a) that measured 6.5 × 6.5 cm2 after falling down to the floor with initial impression of cellulitis. Easy bruising, multiple ecchymoses (Fig. b), joint hypermobility (Fig. c) and poly-arthralgia were noted since childhood; however, no specific medical advice was sought before the clinic visit. Clinical examination revealed body height 108 cm (23th percentile) and body weight 21 kg (75th percentile). The patient had joint hypermobility, Beighton score 7 (including bilaterally passive dorsiflexion of fifth finger beyond 90, score 2; bilaterally passive flexion of thumb to forearm, score 2; hyperextension of the elbow beyond 10 degree, score 0; bilateral hyperextension of the knee beyond 10 degree, score 2; forward flexion of the trunk with knees fully extended and palms resting on the floor, score 1) [], poly-arthralgia without inflammatory signs, mildly hyperextensible skin, and ecchymoses over multiple sites. Among the minor diagnostic criteria for cEDS, muscle hypotonia, delayed gross motor development, easy bruising without obvious causes, and positive family history (similar symptoms of joint hypermobility in his father and aunt) were also observed. Chest wall deformity, kyphoscoliotic posture, periodontal lesions were not observed during physical examination. No tumors and vasculopathy were observed on ultrasound and magnetic resonance imaging of the pretibial mass. Echocardiographic assessment revealed no mitral valve prolapse and aortic root dilatation. The myopathy was less likely due to normal range creatine kinase. Hematological studies for coagulation and platelet disorders and study for autoimmune diseases all provided normal results (Supplementary Table. ). With aforementioned presentation, the patient was suspected of having EDS. Skin biopsy was performed, and whitish subcutaneous fat spheroids were observed during the biopsy (Fig. d). Light microscopy revealed fibrosis in the subcutaneous fat and organizing haematoma without malignancy. Transmission electron microscopy of the skin biopsy revealed irregular interfibrillar spaces, collagen fibers with variable diameter, and collagen cauliflowers (Fig. e) []. Molecular evaluation of genomic DNA extracted from a blood sample was performed. Whole exome sequencing and conventional Sanger sequencing were performed using the CytoOnearray sequencing panel (Phalanx Biotech, Taiwan). These analyses identified the frameshift mutation NM_000093.4(COL5A1):c.4211_4212delAG in exon 54, which resulted in a glutamine to arginine substitution at codon 1404 [NP_000084.3: p.Gln1404ArgfsTer77] (Fig. ). Based on disease-causing mutation databases, such as Leiden Open Variation Database (LOVD) [] and ClinVar [], this frameshift mutation identified in our patient is a novel finding. At least 45 pathologic variants of a frameshift mutation in cEDS have been found; however, no pathological variants and mutation loci were detected, as in our patient. This is a novel frameshift mutation in CO5A1 first identified in this patient with cEDS. This patient was regularly followed in the multidisciplinary team and accepted the rehabilitation program in outpatient clinic.


An eight-year-old boy without significant past medical history was brought to the outpatient department by his parents with a four-day history of non-documented, low-grade intermittent fever, which became persistent from the very next day. There were no associated symptoms at the time of the presentation. Additionally, parents reported no history of sore throat, cough, nausea, vomiting, and bowel and bladder abnormalities. There was no history of any drug intake, contact with a sick patient, or known exposure to someone COVID-19 positive. Initial evaluation revealed a temperature of 99°F, blood pressure (BP) of 115/75 mmHg, heart rate (HR) of 90 beats/minute, respiratory rate (RR) of 18 breaths/minute, and oxygen saturation (SpO2) of 98% while breathing ambient air.
The patient was discharged on acetaminophen (Tylenol). The next day, the patient presented with a fever again, but this fever was accompanied by lethargy and tachypnea. He also developed mild-to-moderate maculopapular eruptions all over the body with sandpaper-like texture and a mild degree of bilateral conjunctivitis.
He was admitted to the pediatric floor, and per hospital protocol, reverse transcriptase-polymerase chain reaction for COVID-19 was also advised along with other laboratory investigations. Physical examination at the time of the second presentation demonstrated a temperature of 100°F, BP of 105/75 mmHg, HR of 95 beats/minute, RR of 27 breaths/minute, and SpO2 of 91%. His workup revealed the following: white blood cell count of 10 x 109/L, a prothrombin time of 19.3 seconds, an activated partial thromboplastin time of 33.2 seconds, C-reactive protein (CRP) of 41 mg/L, an erythrocyte sedimentation rate (ESR) of 30, and a D-dimer concentration of 1.8 µg/ml. A chest x-ray (CXR) showed a parenchymal opacification in the left upper lobe with pleural effusion on the same side (Figure ). His COVID-19 test result was negative.
The patient was empirically started on 1.2 g of intravenous (IV) ceftriaxone and 320 mg of IV vancomycin three times per day in normal saline at a slow rate. In addition, echocardiography was performed. On the following day, his fever was 101°F, and his SpO2 started dropping dramatically to 85% along with worsening tachypnea. He was started on supplemental oxygen at 2 L/min via face mask. A portable CXR was done, which showed worsened inflammatory changes with local patchy infiltrates in the right middle lobe (Figure ).
The echocardiography findings were unremarkable. Blood serology for measles was negative. Additionally, a strep throat test result was negative. After carefully ruling out all possible differentials like a drug-induced allergic reaction and infections (e.g., SSSS, scarlet fever, measles, varicella), the patient was highly suspected of having atypical KD based on the clinical presentation and history of fever. He was also started on high-dose IV immunoglobulins (IVIG) at 2 g/kg on day one (given the patient weighed 24 kg) along with a high dose of aspirin (80 mg/kg/day every six hours) as per guidelines. Moreover, an anti-severe acute respiratory syndrome-coronavirus-2 serologic test result was positive, with an immunoglobulin G titer level of 2.1. Hence, he was diagnosed with COVID-19-associated atypical KD.
Twenty-four hours after completion of IVIG, his breathing issues started resolving. His repeated CXR showed mild inflammatory changes without any new lung infiltrates or lesions. Additionally, his fever also subsided, and the rash started disappearing. His daily temperature chart is shown in Figure . On day six, he was discharged from the hospital on a low dose aspirin of (5 mg/kg/day) as maintenance therapy. On his follow-up visit, the patient was doing well.


A 64-year-old man suddenly developed severe dysarthria 2 days before admission. Neurological examination revealed no other deficit. There was no risk factor for stroke, except hypertension. The patient was under regular medication of calcium channel blocker and his blood pressure was well-controlled. Diffusion-weighted image revealed symmetric high-signal intensity in bilateral paramedian pontine (Fig. A). The midline of basis pontis was spared. The magnetic resonance angiography displayed fenestration of the proximal mid-BA (Fig. B). High-resolution magnetic resonance image (HRMRI) showed endothelium-lined partial intraluminal septa within the fenestrated artery at the level of bilateral symmetric pontine infarction (Fig. C). No atheroma was observed from HRMRI. Flow dynamic study with GTflow (GyroTools, Winterthur, Switzerland) was performed. Flow was divided at the fenestrated area (Fig. D). Flow velocity and wall shear stress was measured at before, after, and at the level of fenestration (Fig. E). Among those 3 points, peak flow velocity was highest and the wall shear stress was lowest at the area of fenestration (Fig. F). Aspirin and cilostazol were started and 3 months later patient was maintained with cilostazol mono therapy. Calcium channel blocker was reused after the acute period of stroke. Blood pressure was controlled under 130/80 mmHg. Dysarthria improved and no stroke recurrence was observed during the follow-up.


A 15-year-old male presented to the clinic with a complaint of right hip pain and decreased range of motion of his hip. A detailed history was performed, which included the patient recalling an injury 18 months prior when he was playing in a nonorganized soccer match. He felt a muscle pull in his right groin. He took a break from playing but resumed after a 10-minute rest. Due to continued pain he eventually stopped playing for the day. Over the next year, he noticed an increased difficulty with hip flexion especially with squatting and kicking a soccer ball with an associated increase in pain. He presented to our clinic for evaluation 18 months after the initial injury. We were the first doctors to see him regarding his right hip injury.
On physical examination, there was a large hard mass in the area of his right groin. His hip flexion was limited to 70 degrees on the injured extremity compared to 120 degrees on the contralateral side. He had 0 degrees of external rotation. However, he still had 40 degrees of internal rotation.
Imaging with X-rays was remarkable for a large heterotopic bone mass at the AIIS that extended 117 mm distal to the AIIS and a maximum lateral distance of 64 mm (). Computed tomography (CT) imaging was obtained, which confirmed our suspicion of the diagnosis of an AIIS avulsion fracture with a 117 mm × 65 mm bony “mass” (Figures and ). At this time, his diagnosis was consistent with extra-articular subspinal impingement. The patient failed 6 months of conservative management including physical therapy, activity modification, and nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, surgical treatment for excision of the mass was offered.
We proceeded to the operating theater and removed the heterotopic ossification through an anterior Smith-Peterson approach to the hip (). We found that a large part of the origination of the rectus femoris was still attached to the distal aspect of the mass. This was detached and tenodesed. Postoperatively, the patient was placed on a course of indomethacin for 1 month. He returned to playing soccer after his two-month follow-up visit. The postoperative X-rays at one-year follow-up demonstrated no new bone deposition (). He had 120-degree hip flexion and full internal and external ranges of motion at his two-year follow-up visit. Importantly, the patient rated his pain at 0/10 at his 2-month, 12-month, and 24-month postoperative visits.


The 67-year-old man who last January 2020 presented to the Emergency Department of our hospital for relapse of heart failure (HF) was already known to our Cardiology Unit. His medical history had begun in 2015 with an acute anterior myocardial infarction, treated with percutaneous angioplasty and stenting on left anterior descending coronary artery. That time, a CMR had been performed before discharge, showing a mildly dilated left ventricle (LV), slight decrease of LV systolic function (LV ejection fraction [EF] 47%) and a subendocardial late gadolinium enhancement (LGE) involving the apical and septal segments. Five years later, because of a new-onset atrial flutter and a severe pleural effusion (Fig. a, b), he had been admitted again to our hospital. Echocardiogram had revealed the signs of the previous apical myocardial infarction, and besides, a biventricular hypertrophy (LV mass 116 g/m2, interventricular septal and posterior wall thickness 1.1 cm and 1.4 cm, respectively), LV high filling pressures (E/E′ 27) and a severe biatrial enlargement (left and right atrial volume 56 cm3 and 51 cm3, respectively) (Fig. ). Pleural effusion had been treated with thoracentesis. Because of the telemetry detection of high-degree atrio-ventricular block with long pauses (> 6 s), a single-chamber pacemaker had been implanted. Six months after the discharge, he came again for fatigue and dyspnea. Laboratory tests showed high cardiac troponin and high B-type natriuretic peptide, and the recurrence of severe pleural effusion required a thoracic drainage. Given the rise of troponin, and the echocardiographic worsening of LV EF, coronary angiography was repeated, showing a critical three-vessel disease. For testing myocardial viability and proceeding to coronary revascularization, CMR was performed and, despite image artifacts due to pacemaker, showed a hypertrophic LV with reduced systolic function (LV mass 97 g/m2, LV EF 35%) due to diffuse akinesia (Fig. a; Additional file : Video 1). Pleura and pericardium effusion were well appreciable. Inversion time scout sequence was not able to identify the appropriate inversion time to null normal myocardium (Additional file : Video 2), suggesting an abnormal gadolinium kinetics. Post contrast images detected a diffuse transmural LGE (Fig. b, c), a pattern which raised the suspicion of CA. However, a subsequent BS with technetium-99 m-3,3-diphosphono-1,2 propanodicarboxylic acid (99mTc-DPD) did not detect any cardiac uptake of tracer (Fig. c). AL amyloidosis was ruled out by urine and serum immunofixation. A careful revision of the CMR findings, combined with the recent medical history, forced us to perform EMB, which at first sight showed replacement-type fibrosis and no evidence of amyloid deposits at Congo Red staining under polarized light microscope as well as at thioflavin T fluorescence []. Despite this, given the high clinical suspicion of CA, immunoelectron microscopy against kappa and lambda light chains and TTR was performed, showing some TTR amyloid fibrils deposits with diameters of about 9 nm in the extracellular matrix of the myocardium (Fig. ). A genetic testing was then performed, but no pathogenic variants were detected, so that a wild type TTR-CA diagnosis was made. The patient was then discharged with anticoagulant, aspirin, statin, diuretic and mineralocorticoid receptor antagonist therapy, and referred to a tertiary care center for evaluation of TTR-targeted treatment. At 6-months follow up, he did not experience readmissions to hospital for HF.


A 27-year-old male presented at the emergency department on September 10, 2015. The chief complaint was neck and shoulder pain for a week after sleeping against the wall with cervical proneness for 1 night. On admission, he had sudden headache, dizziness, nausea, slurred speech, a skewed mouth, and left side weakness, for 1.5 hours. He was 187 cm tall with about 45 kg in weight, and had disproportionately slender limbs, thin wrists and long fingers and toes. Neurologic examination revealed speech impairment and left-sided weakness (National Institute of Health stroke scale [NIHSS] = 10). He underwent mild reversion of the mitral valve many years ago. The patient denied any cocaine or amphetamine abuse. No other medical history was positive. Family history was not remarkable. Blood test indicated homocysteine at 17.4 μmol/L (normal ranges, 0–15 μmol/L), anti-myeloperoxidase antibody and protease 3 both at levels <2.00 IU/mL (normal ranges, 0–20 IU/mL), and rheumatoid factor levels at 9.19 IU/mL (normal ranges, 0–15.9 IU/mL). Other blood parameters were within the respective normal ranges. Abdominal ultrasound showed no abnormality.
Head computed tomography performed 15 minutes upon admission was unremarkable. Then, the patient underwent MRI 1.5 hours after admission, and ischemic areas were detected in the pons and the cerebellum (Fig. ). T1 weighted sequence showed high signals for the left vertebral artery (VA) and the basilar artery wall, indicating hematoma (Fig. ). MRA showed irregular and narrowed basilar artery and origin of posterior cerebral artery (P1 segment) (Fig. ). The patient was diagnosed with acute cerebellar and pons stroke. Within 4 hours of symptom onset, intravenous thrombolytic therapy was initiated. For treatment, recombinant tissue plasminogen activator at the standard dose of 0.9 mg/kg was administered (initial 10% of the total dose as a bolus over 1 minute, and the remaining dose over 60 minutes). Left side weakness symptoms were improved 30 minutes after the treatment. Emergency DSA confirmed the initial MRI and MRA findings, showing bilateral intraluminal filling defects in the V2 segment of VAs. The left VA was occluded, while the right one was irregular and narrowed (Fig. ).
Neurologic symptoms were improved significantly after the treatment (NIHSS = 6). Control computed tomography examination at 14 hours ruled out intracranial and cervical hemorrhage. High resolution-MRI revealed irregular stenosis and intimal flap in the right VA and left VA occlusion, which are dissection signs (Fig. ). Anticoagulant therapy was started with low molecular weight heparin calcium (Fraxiparine, GlaxoSmithKline) (0.4 mL; hypodermic injection; q12h∗12 days). On the sixth day, oral Dabigatran was added at 110 mg bid for 9 days. Combination of both drugs was further administered for 7 days. After discharge, the patient was prescribed oral Dabigatran for 6 months at 110 and 160 mg mornings and evenings, respectively. The patient recovered well 3 days after the stroke (NIHSS = 0). Marfan syndrome was considered. FBN1 gene test was negative. In subsequent DSA examinations performed 3 months after stroke, the lumen of the right VA had almost returned to normal (Fig. ) with left VA occlusion finally remaining. He recovered well and had no recurrence in the subsequent 4 years of follow-up.
This study was approved by the Ethics Standard Committee on Human Experimentation at Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong. Research has been conducted in accordance with the principles expressed in the declaration of Helsinki and its later amendments. The current patient provided informed consent to report this case.


A 76-year-old woman visited the Emergency Room complaining of swelling, redness, and warmth on the left anterior chest wall for 4 days. She had a medical history of cerebral infarction 15 years ago, and had since been taking aspirin and clopidogrel. She had been diagnosed with endometrial cancer and had undergone hysterectomy 8 years ago, which had been followed by chemotherapy and radiotherapy. Moreover, she had developed a lumbar spine tumor 7 years ago and had subsequently undergone radiotherapy, although she and her family were unaware of the pathological diagnosis of the tumor. Both her cancers were completely treated. Three months before visiting our hospital, she had been diagnosed with delirium and was taking risperidone and donepezil. She did not have history of diabetes mellitus or hypertension. Her estimated glomerular filtration rate was slightly decreased to 43.8 mL/min/1.73 m2. The patient appeared acutely ill. There was no cardiac murmur on auscultation. Her initial blood pressure was 107/56 mm Hg, heart rate was 96 beats per minute, respiratory rate was 24 breaths per minute, and body temperature was 38.1°C. Her white blood cell count was 6.5 × 109/L (normal range: 4.0–10.0 × 109/L), with 82.3% neutrophils (normal range: 40.0–75.0%); her C-reactive protein level (CRP) was 25.08 mg/dL (normal range: 0–0.5 mg/dL) and ESR was 127 mm/h (normal range: 1–22 mm/h). Physical examination revealed no abnormalities in her teeth or throat. Cardiac echocardiography reveled no vegetation or structural abnormalities on the valves. Magnetic resonance imaging showed infectious arthritis in the left SCJ, with multiple abscess pockets measuring 3.2 cm × 3 cm × 1 cm at the subcutaneous layer of anterior chest wall communicating with the joint cavity (Fig. A and B). In addition, small abscesses were observed posterior to the left SCJ and sternum, and posterior to the clavicle. Osteomyelitis was observed at the sternum, and erosions were observed in the clavicle. Ultrasound-guided aspiration of the joint fluid for culture was performed. Cefazolin was initially started, empirically targeting methicillin-susceptible S aureus (MSSA), which is the most common pathogen of SCJ septic arthritis.
Penicillin-sensitive (minimum inhibitory concentration ≤0.12) Streptococcus agalactiae was isolated on both peripheral blood and aspirated joint fluid. The sensitivity of S agalactiae is shown in Figure . The antibiotic was switched to penicillin G 24 million units per day. After 2 weeks of treatment, the CRP level of the patient decreased from 25.08 to 1.67 mg/dL (Fig. ). However, she developed leukopenia and thrombocytopenia, which were suspected to be the side effects of penicillin. Despite changing the antibiotic to cefazolin, her leukopenia worsened. Subsequently, cefazolin was replaced by vancomycin, and the treatment was continued for another 2 weeks. After a total treatment duration of 6 weeks, the CRP level of the patient decreased to the normal range (0.25 mg/dL), and follow-up computed tomography of the chest showed improved SCJ swelling and abscess (Fig. C and D). She was discharged, and she did not show any signs of recurrence after 3 months, after which she was lost to follow-up.
The daughter-in-law of the patient has provided informed consent for publication of the case (attached as supplement).