A 39-year-old, Caucasian 1G0P0A0T woman at 5 Gestational Weeks (GW) consulted with a chief complaint of a non-desired pregnancy. She also complained about an indolent swelling of the right interlabial fossa measuring 7 × 3 × 3 cm. The mass has not significantly changed in 9 years. Her medical history was unremarkable. Her sexual history revealed no dyspareunia and physiological sexual response. On physical examination, we observed a soft, painless bi-lobated fluid-filled swelling of the right interlabial fossa slightly diverting the clitoris on the opposite side (Fig. ). Speculum, digital and general examination were normal.
A transvaginal ultrasound was performed for pregnancy datation and localization, which confirmed an intrauterine pregnancy of 5 + 3/7 GW. According to the patient’s request, surgical excision of the cyst combined with dilation and curettage was performed. Dilation and curettage were uneventful. During the enucleation of the cyst, we saw a clear mucinous fluid dripping off because the cyst wall was very thin. We applied a Foley catheter swollen with 5 cc of NaCl to maintain a proper cleavage plan of the lesion. Cystectomy was uneventful. The specimen was sent for pathological analysis which identified an 8 × 2 × 1.5-cm cyst of the Bartholin’s gland. Surprisingly, after the excision of the first cyst, we noticed a second smaller mass of 1.5 cm adherent to the right side of the body of the clitoris. The mass had an adipose aspect at sight and consistence at palpation (Fig. ). We proceeded to the ablation of the second cyst (Fig. ), respecting the clitoris’ neurovascular bundle. Pathological analysis revealed a 2 × 1.5 × 1.5-cm benign leiomyoma arising from the right side of the clitoris (Fig. ). The immediate postoperative period was uneventful and the patient was discharged on day 1. Our patient presented with a defect of the cystectomy scar that required surgical correction 6 months after the first surgery, with full recovery (Fig. ). Considering the genetic implications of an extrauterine leiomyoma, we offered our patient a genetic consultation, which she declined.


A 14-year-old female of Lebanese origin, presented with B-symptoms and multiple enlarged lymph nodes on the right side of the neck. Fine-needle aspiration suggested plasma cells or cells with thyroid or paraganglioma origin. A lymph node biopsy was taken and histology showed MTC metastasis. After this, basal calcitonin was measured to 18.3 μg/L (<0.1 μg/L). The patient underwent a total thyroidectomy and right-sided neck dissection. Histology displayed multifocal MTC (largest tumor 7 mm) with metastases to 17 of 20 removed lymph nodes and a normal parathyroid gland. The final TNM-stage was T1aN1bM0. Two months postoperatively basal calcitonin was 19.0 μg/L (<0.1 μg/L) and adjuvant radiotherapy was given. RET testing revealed the L790F (c.2370G>T) germline mutation. There was no family history of MEN 2A. The father was tested negative for RET mutations, while the mother was positive for the L790F mutation. The latter, however, declined further work up. Fourteen years later basal calcitonin had risen to 59,280 ng/L (<7.3 ng/L). Distant metastases were cytologically verified in mediastinal lymph nodes and suspected in the neck, lungs, mamma, liver, and in proximity to the transverse colon. The patient was initiated on Vandetanib, a tyrosine kinase inhibitor. Thirty months after initiation, the patient had basal calcitonin of 80 ng/L and apart from the suspected liver metastasis that was assessed without change there were no radiological evidence of metastases on CT scan. Neither pheochromocytoma nor primary hyperparathyroidism has been diagnosed during the 16 years of follow-up. shows clinical characteristics and results of genetic analyses for patient 1.


A 70-year-old female, presented with a right-sided thyroid tumor, but was otherwise asymptomatic. Fine-needle aspiration showed follicular neoplasm of unknown malignant potential. The medical history was unremarkable apart from a right-sided ductal carcinoma in situ treated with lumpectomy and radiotherapy 18 months earlier. The patient underwent a left-sided hemithyroidectomy without prior measurement of serum calcitonin, as MTC was unsuspected. Histology revealed multifocal MTC with the largest tumor size of 15 mm. At this point, basal serum calcitonin was 28 ng/L (<7.3 ng/L) and family history revealed that the mother and aunt had undergone thyroid operations for unknown causes. The patient underwent right-sided completion thyroidectomy. Histology showed multifocal MTC with several tumors measuring 1–3 mm. Also, a removed lymph node was without metastasis. The final TNM-stage was T1bN0M0. A RET test identified the L790F (c.2370G>T) germline mutation. Subsequently, normal tissue from the deceased mother was also tested positive for the L790F mutation. Basal serum calcitonin was immeasurable and no biochemical signs of pheochromocytoma or primary hyperparathyroidism have been present after 1 year of follow-up. Clinical characteristics and results of genetic analyses for patient 2 can be seen in .


A 67 year-old Japanese man was referred to our hospital for the treatment of diabetes with the concomitant concern about his severe hypouricemia. He was admitted to our hospital and biochemical data were collected under hospitalized conditions. On admission, his body mass index (BMI) was 25.1 (height: 174.1 cm, weight: 76.2 kg), excluding the possible contributions of obesity-induced alteration of urate metabolism. Although the historical onset and progression of his hypouricemia was unclear, he exhibited severe hypouricemia with hyperuricosuria (serum urate levels: 0.7 mg/dl (3.8–7.0 mg/dl) (41.6 μmol/l (226–416 μmol/l)), fractional excretion of urate (FEUA) was 65.5%) without any signs of kidney dysfunction (serum creatinine levels: 0.7 mg/dl, creatinine clearance: 109.1 ml/min, estimated glomerular filtration rate (eGFR): 85.4 ml/min/1.73m2). His urinary fractional excretion of urates was elevated but relatively modest compared to the reported cases of severe hypouricemia [, ]. He did not have any past medical history of either nephrolithiasis or exercise-induced acute renal failure to which hypouricemia sometimes predisposes [].
We also assessed his glucose metabolism biochemically. On admission, he was treated with 25 units of insulin degludec with 1500 mg of metformin, 20 mg of teneligliptin and 20 mg of tohogliflozin with 8.9% of glycated hemoglobin (HbA1c) levels. Fasting and postprandial serum C-peptide levels-blood glucose levels were 0.09 ng/ml - 5.67 mmol/l, 1.45 ng/ml - 13.0 mmol/l, respectively while his urinary excretion of C-peptide was 25.7 μg/day, indicating impaired insulin secretion. Glutamate decarboxylase (GAD) auto-antibody was negative, and he did not have any medical histories of autoimmune diseases, excluding the possibility of autoimmune diabetes.


A five-year-old male non-Caucasian patient presented with fever, myalgia, headache, and conjunctivitis for 5 days. His past medical history was unremarkable, with normal psychomotor development, no family history neurological diseases and no consanguinity. The patient was born and lived in Ceará, northeast Brazil, and family reported no recent travels.
After 1 week he developed tonic-clonic seizures. Neurological examination was normal at this point. Complete blood count, liver functions and acute reactants were normal. Serologies for HSV-1, HSV-2, CMV, EBV, VZV, HIV, and toxoplasmosis were negative. Brain MRI was normal. Cerebrospinal fluid analysis revealed 15 cells, protein 16.6 mg/dL and glucose 68 mg/dL. He was started on acyclovir and ceftriaxone.
Two weeks after seizure onset, he presented with dystonia () and oromandibular dyskinesia. On physical examination the patient was awake, his speech output was decreased, pupils were normal. Cranial nerves examination was unremarkable. Muscle strength was symmetric and deep tendon reflexes were normoactive and symmetric. One week later he developed focal motor seizures followed by decreased level of consciousness, dysautonomia, and central apnea. EEG showed extreme delta brush and valproate and phenytoin were started. He also received methylprednisolone followed by intravenous immunoglobulin with seizure resolution and improvement of level of consciousness, dysautonomia and orofacial dyskinesias within 2 weeks.
Anti-NMDAR antibodies were detected in serum (titer 1:25600) and CSF (titer 1:1024) after 3 weeks of symptom onset using tissue and cell-based assays as previously reported (). CHIK serology was positive for both IgM and IgG, suggesting a recent infection. Dengue and Zika serologies were negative. CSF PCR for herpes viruses and arboviruses (CHIK, Dengue and Zika) were negative. Whole body CT and testis ultrasound were normal. Because of partial improvement (persistence of orofacial dyskinesias and impaired speech), the patient received rituximab and cyclophosphamide with good response. After 8 months he is seizure-free and has returned to school with only mild restlessness and inattention. describes the timeline of clinical features, investigation and treatment of the case report.


A 24-year-old Hispanic male presented to outpatient clinics with a past medical history of a persistent cough and shortness of breath for 10 years. Recently, his symptoms progressively worsened to chronic hypoxemic respiratory failure. He required long-term supplemental oxygen therapy of 5 liters/minute by nasal cannula and high flows of up to 15 liters/minute during pulmonary rehabilitation. His pulmonary function tests revealed a markedly decreased forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO), which were only 35% and 34% of predicted, respectively. Computed tomography (CT) of the chest revealed diffuse ground glass opacities, punctate calcifications, and extensive subpleural cysts consistent with PAM (). A prominent pulmonary trunk, right cardiac chamber dilation, and mild interventricular septum straightening suggested a component of pulmonary artery hypertension. Right heart catheterization confirmed pulmonary artery hypertension with normal cardiac output and cardiac index. Because of his progressive symptoms with significant oxygen requirements, he underwent bilateral lung transplantation.
Gross examination of the bilateral pneumonectomy specimens revealed enlarged lungs (right lung 1750 grams, left lung 1438 grams). The pink-tan pleural surfaces had multiple small plaque-like structures. The cut surfaces were pink-red and spongy with a gritty, sand-like texture (). Hematoxylin- and eosin-stained sections revealed the characteristic diffuse intra-alveolar lamellar microliths (). The background lung parenchyma showed interstitial fibrosis, numerous hemosiderin-laden macrophages, interstitial inflammation, and acute pleuritis.
His lung transplantation was complicated by intraoperative hemorrhage requiring >20 units of red cells and various other blood products. His hospital course was complicated by persistent leukocytosis and stenosis to the left mainstem bronchus, mucosal ischemia, and recurrent mucous plugging requiring repeated bronchoscopies. At 1 year post transplant, his pulmonary function tests revealed an improved FVC and DLCO of 50% and 76% of predicted, respectively. Since PAM has an autosomal pattern of inheritance, family screening was being considered for this patient.


A seven-day-old male presented to pediatric urology with antenatally diagnosed right hydronephrosis with a severely dilated ureter. A follow-up ultrasound one month later demonstrated increased ureteral dilation which was further evaluated with a voiding cystourethrogram which was normal, and a renogram which demonstrated approximately equal differential function with obstruction. He was initially managed with serial renal ultrasound and observation. Follow-up ultrasound at six months of age demonstrated concern for possible duplication of the right collecting system (Figure ).
Cystoscopy at eight months of age revealed a single right and left ureteral orifice orthotopically located. Left retrograde pyelogram was normal. Right retrograde pyelogram revealed a non-dilated but deviated right upper pole ureter (Figure ). The right lower pole ureteral orifice was not identified.
Magnetic resonance urography confirmed a duplicated collecting system on the right with upper pole hydronephrosis and a tortuous ureter due to displacement by the massively dilated lower pole ectopic ureter and scarring of the lower pole renal moiety (Figures , ).
He had normal renal function with a creatinine of <0.15 mg/dl. Due to the space-occupying nature of the right lower pole ureter, surgical excision with right lower pole heminephrectomy with ureterectomy was pursued. Intraoperatively, the right lower pole ureter was massively dilated causing displacement of the upper pole ureter, small bowel, and ascending colon (Figure ).
There was visible lower pole moiety renal parenchymal tissue or dilated collecting system associated with the ureter, so the ureter was ligated where it appeared to arise from the normal appearing renal parenchyma of the upper pole moiety (Figure ). The proximal segment of the ureter was excised down to the level of the iliac vessels. The distal segment of the ureter was marsupialized. The ectopic insertion of the lower pole ureter was unable to be visualized.
His postoperative course was uneventful, and he was discharged home on postoperative day 2. Pathology revealed ureteral tissue with hypertrophy of the muscularis, fibrosis, and patchy mild chronic inflammation consistent with a duplicated blind ending ureter.


A 51-year-old female travelled from Illinois to Colorado for a winter vacation with her family. She was a previous smoker (< 1 pack/day) and had been abstinent for more than 10 years. Past medical history consisted of a remote Caesarean section, medically controlled hypertension, no know allergies, and minimal social alcohol consumption. On March 6, 2020, she presented with an unstable ankle fracture to a local hospital and underwent surgery by open reduction with internal fixation the following day. Prior to her surgery, she had reported “mild cold symptoms”. Upon awakening from general anesthesia, during extubation she was noted to have an unusual consistency of her respiratory secretions described as “pink and frothy”. Empirical broad-spectrum antibiotics were initiated for the treatment of a presumed aspiration pneumonitis. The patient deteriorated over the subsequent days with fever, hypoxemia, and bilateral pulmonary infiltrates. She required intubation and mechanical ventilation. COVID-19 testing was performed by nasopharyngeal swab and was positive for SARS-CoV-2 by polymerase chain reaction (PCR). The patient was transferred to our center, an established ECMO program, for higher level of care 1 week after her initial admission.
The timeline of the patient’s course of events is summarized in Table .
Upon arrival to our facility, she was hemodynamically stable, sedated, intubated and mechanically ventilated on 60% FiO2 and 10 cm H2O positive end-expiratory pressure (PEEP). Figure demonstrates the patient’s chest X-ray on admission. She was admitted to our designated COVID-cohorting unit in the ICU and placed with strict respiratory droplet isolation precautions in a negative airflow room. Her admission laboratory studies demonstrated a low white blood cell count of 3110/μL with lymphocytopenia (22.5% or 700/μL). A bedside transthoracic echocardiogram showed normal left and right ventricular function, no valvular abnormalities, and normal estimated pulmonary artery pressures. By hospital day 2, her oxygen requirements increased and intermittent prone positioning was initiated in conjunction with pharmacologic paralysis and inhaled nitric oxide treatment.
Within the next few days, the patient’s pulmonary compliance and hypoxemia worsened. Isolated end-organ pulmonary dysfunction persisted despite maximal ventilator support resulting in a PaO2/FiO2 ratio of 66 while still receiving inhaled nitric oxide iNO at 40 ppm. The arterial blood gas analysis (ABGA) showed a pH 7.36, pCO2 45 mmHg, and pO2 66 mmHg. The patient had a calculated “Respiratory ECMO Survival Prediction” (RESP) score of 1 with a risk class III and an estimated ECMO survival probability of 57% [].
Percutaneous femoral-femoral veno-venous ECMO support was initiated on day 7 of hospitalization. In brief, following systemic heparinization (10,000 units; maintenance target PTT 40–60 s), cannulation was accomplished with a 21-French venous multi-stage drain and a 21-French single-stage inflow cannula connected to a CardioHelp™ extra-corporeal support system (Maquet Cardiovascular, Wayne, NJ). Initial ECMO settings were 3.8 l/min flow, 3.2 l of gas sweep, and ECMO FiO2 of 1.0. A lung protective ventilator strategy was initiated with an airway pressure release ventilation (APRV) mode (rate: 16, pressures: 28/10, FiO2: 0.8, inhaled nitric: 20 ppm, and plateau pressures were limited to 30 mmHg). Antiviral therapy with remdesivir (RDV / GS-5734; Gilead Sciences Inc., Foster City, CA) was initiated on hospital day 9 under a humanitarian use protocol for “compassionate use” indication [], with a loading dose of 200 mg RDV intravenous on the first day, and once-daily maintenance doses of 100 mg RDV intravenous for a total treatment duration of 10 days.
A repeat echocardiogram showed no change in her left or right ventricular size or function. A bedside ultrasound demonstrated increasing bilateral pleural effusions which were managed by percutaneous drainage with bilateral 14-French chest tubes. The patient’s pulmonary compliance, oxygenation, and ventilation, gradually improved over the subsequent days, and the ECMO sweep was slowly weaned (ventilator settings at pressure control; mean airway: 25 mmHg; rate 25; FiO2 0.50; inhaled nitric oxide 20 ppm). Subsequently, the ECMO gas sweep was weaned off and the patient was successfully decannulated at the bedside on ECMO day 11 (hospital day 17). Her overall pulmonary function improved to the point in which she was extubated to heated high-flow oxygen. The patient’s oxygen requirements were weaned to 2 l nasal cannula on post-ECMO day 4 (hospital day 21). Room air blood gas analysis revealed pH 7.46; pCO2 33.6 mmHg; pO2 74.4 mmHg; HCO3–23 mEq/L, SO2 94%. A limited bedside spirometry yielded a negative inspiratory force (NIF) of − 50 mmHg.
Two repeat COVID-19 tests were negative for SARS-CoV-2 prior to discharge form the hospital. The patient was discharged to a rehabilitation facility on hospital day 28 requiring 2–3 l/minute of supplement oxygen which was weaned to room air within the week. At discharge, she was weak but able to stand and walk short distances and had an otherwise normal neurologic examination. Upon discharge she was greeted by a large group of health care providers as part of a farewell ceremony for our COVID-19 survivor (Fig. ).


A 77-year-old male patient with a history of chronic obstructive pulmonary disease was referred to our emergency department as a heart attack case. He presented 4 days of progressively intense pain in the right lower quadrant along with a syncopal episode preceded by dyspnea and oppressive thoracic pain. In the remission site troponin was positive and the electrocardiogram (ECG) was normal; This required initial anti ischemic management and transfer to our service. Upon admission his abdomen showed marked abdominal distension with peritoneal irritation signs, absent bowel sounds and an incarcerated hernia in this level. The patient did not report thoracic pain or dyspnea during the physical exam and the cardiopulmonary auscultation was normal.
The ECG () showed Q waves in DII, DIII and AVF, negative T waves in VI V2 and V3 without alteration of the ST segment. The laboratories showed an ultrasensitive positive troponin of 0.040 with a delta positive at 0.030, The blood count, renal function, electrolytes and arterial gases were normal.
A transthoracic echocardiogram showed a moderate dilatation of the right ventricle with signs of pressure and pulmonary hypertension without contractility disorders. The complementary computed tomography (CT) showed findings of acute appendicitis and probable Amyand’s Hernia ().
The treatment consisted of oral restriction, antibiotics, analgesia, and hydration. This combination was highly approved by the cardiology and surgical teams who decided to perform an emergency laparotomy. The intraoperative findings included a right inguino-scrotal hernia incarcerated with a necrotized hernia sac that contained the cecal appendix which was gangrenous and perforated, with significant tissue edema in the right inguinal region, blind, parietal peritoneum with pelvic peritonitis (, ). The patient required Intensive Care with invasive ventilatory support and vasopressor.
With managed multidisciplinary care by intensivists, cardiologists, nutritional support and surgeons, the patient presented an evolution of improvement, achieving, on the second postoperative day, removal of the ventilatory and vasopressor support. He was transferred to the hospitalization area and administered a liquid diet, analgesia and cardiac catheterization to establish the etiology of the MI. Acetylsalicylic acid which was added at a dose of 100 mg every day, along with an angiotensin receptor antagonist (ARA II), due to high blood pressure during hospitalization, and anticoagulation with enoxaparin. He was taken for cardiac catheterization with evidence of healthy coronaries and no signs of atherothrombosis which could lead to the diagnosis of MIT2.
His hospitalization lasted about 6 days with a positive outcome. Consequently, he was discharged with antibiotics therapy for 7 days, analgesia as needed and an outpatient’s order controlled by general surgery and cardiology at 10 days presenting an adequate postoperative.


Our patient was a 65-year-old Japanese woman whose NFomas began to appear when she was in elementary school. She was born without any perinatal anomalies. At age 28, she was diagnosed as having NF1. In 2012, a spinal compression fracture was identified during a visit to a local orthopedic surgeon for lumbago. In 2017, she visited a local orthopedic surgeon with a chief complaint of lateral chest pain, and multiple rib fractures were identified. Hence, she was referred to our department for endocrinological examination. Pregabalin 50 mg was administered daily, and loxoprofen sodium hydrate 60 mg was used at the time of pain.
She was 147.1 cm tall, weighed 47.5 kg, body mass index was 22.0 kg/m2, body temperature was 36.6 °C, blood pressure was 105/72 mmHg, and pulse was 72 beats/minute and regular. She showed no mental retardation, and no pigmentation on her skin and oral mucosa. Her cardiopulmonary examination was normal. She had no abnormal abdominal and neurological findings or skeletal abnormalities. Soft NFomas of various sizes were scattered all over her body, and relatively large masses approximately 4 cm in diameter were present on the surface of her right forearm and left upper arm (Fig. ). Her eldest daughter has also been diagnosed as having NF1. She was a caregiver; our patient drank alcohol occasionally but did not smoke tobacco. Her serum levels of inorganic phosphorus (IP), 25(OH)D3, and maximum transport of phosphorus in the renal proximal tubules (TmP/GFR) were inappropriately low (Table ). Serum alkaline phosphatase (ALP), intact parathyroid hormone (intact PTH), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP 5b), and undercarboxylated osteocalcin (ucOC) levels were all elevated. Her serum level of FGF23 was high. The results of total blood cell count and other biochemical parameters were almost within normal limits (Table ). BMD using dual-energy X-ray absorptiometry of the second to fourth lumbar vertebrae (L2–4, total) and left femoral neck were 0.764 g/cm2 and 0.504 g/cm2, with a young adult mean (YAM) of 64% and 54%, respectively. Computed tomography displayed no space occupying lesions other than NFomas on the body surface. Multiple areas of abnormal tracer uptake were seen in her rib on 99technetium (Tc)-methylene diphosphonate bone (MDPB) scintigraphy. Slight abnormal accumulation of tracers was observed in the NFomas located on the surface of her right forearm and left upper arm on 111indium-pentetreotide scintigraphy (Octreoscan) (Fig. ). She did not agree with venous sampling because of difficulty in maintaining her supine position for prolonged periods because of systemic pain. Since she strongly desired resection of the NFomas on her right forearm and left upper arm, we respected her wish and excised them in February 2018. Pathology evaluation demonstrated benign NFomas. Unfortunately, there was no improvement in serum IP levels after surgery. Therefore, we administered eldecalcitol (active vitamin D3 analogue) 0.75 μg per day, which also failed to produce improvement in hypophosphatemia and other abnormal data. Subsequent combination with dibasic calcium phosphate hydrate (3.0 g/day) led to improvement in some of the abnormalities, including hypophosphatemia: IP, 3.1 mg/dL (2.7–4.6); ALP, 209 U/L (106–322); intact PTH, 46 pg/mL (10–65); BAP, 12.4 μg/L (3.8–22.6); and TRACP-5b, 309 mU/dL (120–420) (data not shown). After 6 months, serum calcium, IP, intact PTH, and BAP were 9.1 mg/dL, 3.6 mg/dL, 37 pg/mL, and 14.4 μg/L, respectively, and were stable in the normal range. Furthermore, pain also improved.
Immunohistochemical staining was performed on formalin-fixed and paraffin-embedded tissue from the resected NFomas, which demonstrated FGF23 weak positivity of the NFomas (Fig. ). Pathological processing and evaluation was performed by GenoStaff Co., Ltd. (Tokyo, Japan).
Total ribonucleic acid (RNA) extraction from the formalin-fixed paraffin-embedded tissue samples was performed according to the manufacturer’s instructions. Human pancreas total RNA (Zyagen, San Diego, California, USA) was prepared as a control []. Next, we performed real-time polymerase chain reaction (RT-PCR) testing for housekeeping genes and actin β gene (ACTB), and the fibroblast growth factor 23 gene (FGF23), according to the manufacturers’ instructions. Amplification curve plotting using fluorescence intensity by ABI PRISM SDS 2.4 (Thermo Fisher Scientific Inc., USA) was performed (Fig. ). All samples were amplified in triplicates. Once out of three times, the threshold cycle (CT) value for FGF23 was 35.95 in resected NFomas, but it was not detected in human pancreas (Table ). Unfortunately, these results did not clearly confirm expression of FGF23 in the excised NFomas. These tests were conducted by GeneticLab Co., Ltd. (Sapporo, Japan).


A 28-year-old female presented to Fatmawati Hospital, Jakarta, Indonesia due to progressive tetraparesis accounting for seven months. Initially there was mild neck pain, and then she experienced numbness along with weakness of all four extremities. The symptoms were gradually worsened such that at the time of admission, she could not walk.
A series of radiographic and CT scan depicted multiple vertebral body destruction anteriorly, along with facet joint dislocation and mild retrolisthesis of C4-C5 segments (Figs. , ). MR images of the cervical region was demonstrated pathologic contrast enhancement on C4 to T7 vertebrae, a total of fourteen contiguous segments, with spinal canal stenosis on the level of C4 to T4 and bilateral anterolateral paravertebral soft tissue abscess at the level of C4 to T9 (). Those findings were highly typical of spinal tuberculosis.
The patient was administered anti-tuberculous agents for two months before undergoing one-staged posterior-only debridement, decompression, and instrumentation. Postoperative radiographs demonstrated that the kyphosis was obviously improved (). After the surgery, the patient was put on a cervicothoracic brace. The patient was closely followed up, and after 12 months postoperatively, she regained neurological recovery with only mild residual neck pain. The patient demonstrated a satisfying level of functional improvement as recorded by the Neck Disability Index (NDI) and SF-36 scores of 4/100 and 94%, respectively.
Bony bridge on CT images was discovered at 18 months of follow-up, along with the normal value of erythrocyte sedimentation rate and C-reactive protein; it was the time we discontinued the anti-tuberculous therapy.


A 59-year-old man with alcohol abuse-related liver cirrhosis was treated for refractory ascites (model end-stage liver disease (MELD) score 17) by means of a transjugular intrahepatic portosystemic shunt (TIPS) procedure. The procedure succeeded uneventfully, however, transient right hepatic artery branches opacification was observed during an attempt to position the Colapinto needle within the portal venous tree (Figure ).
The patient was discharged from the operating room with no signs of complications. Two days later, a massive gastrointestinal hemorrhage with associated rettorragia occurred, leading to a significant decrease in hemoglobin (from 12 mg/dl to 6 mg/dl); concomitant increased total bilirubin blood levels was detected (from 10 µmo/L to 290 µmo/L). Computed tomography angiography (CT-A) was performed to assess haemobilia. Arterial phase images revealed contrast media filling of the biliary tree, the choledocus and the duodenum (Figure ).
The patient underwent an attempt at percutaneous embolization. Selective angiography of the celiac trunk revealed an arteriovenous-biliary fistula between the proximal branch of the right hepatic artery, the right hepatic vein, and the right biliary system (Figure and Figure ).
A microcatheter (Progreat 2.7 F; Terumo Corporation, Tokyo, Japan) was advanced within the fistula; contrast media injection confirmed opacification of the hepatic vein, the biliary tree, the choledocus and the duodenum (Figure and Figure ).
Pushable microcoils (0.018 Coils; Boston Scientific, Marlborough, Massachusetts) were released inside the fistulous tract (Figure ).
Final angiogram demonstrated the exclusion of the hepatic vein and the biliary tract and the patency of the right hepatic artery and its distal branches (Figure ).


50-year-old man, accountant, from a town in the countryside of Alagoas. He sought medical attention two years before a nephrological evaluation, complaining of pain in the right iliac and suprapubic fossa, nausea, vomiting and intense dysuria. He had no hematuria, fever, or weight loss. After consultation with an urologist, he used ciprofloxacin and tamsulosin for seven days. With no symptom improvement, the treatment regimen with ciprofloxacin was extended for another 14 days. The following exams were ordered in the investigation: urinary tract ultrasonography, prostate-specific antigen dosage and urodynamics, which results remained within the normality range. Urinalysis showed a pH of 7 and numerous pyocytes; and the erythrocyte sedimentation rate was 75 mm/1st hour. Computed tomography and ultrasound images of the abdomen revealed discrete renal pelvic ectasia and prostate calcifications ( and ).
The initial physical examination of the nephrological evaluation did not detect significant alterations besides discomfort to deep palpation in the hypogastric region. Inflammatory markers, uroculture and EAS were requested for control purposes. Inflammatory markers were altered, leukocyturia persisted in the EAS, and uroculture was repeatedly negative. In this way the possibility of M. tuberculosis urinary infection was raised and specific culture was requested for this infectious agent. Two months later, the patient returned for consultation complaining of persistent dysuria, bladder discomfort (pressure), voiding urgency and nocturia. The uroculture resulted positive for M. abscessus. In the Löwenstein-Jensen solidified medium, fast-growing mycobacteria formed acromogenic colonies with rough-to-smooth morphology. The biochemical tests revealed a reduction of nitrate (-), β-glycosidase (-), 5% tolerance to sodium chloride (+), sodium citrate (-), fructose fermentation (-), mannitol fermentation (-); picric acid (+) and Tween 80 hydrolysis (+).
We started treatment with clarithromycin (500 mg twice daily) and amikacin (15 mg/day), for 18 months. In the fifth month of treatment, the patient remained with urinary symptoms; however, in the tenth month he already showed important improvements. In the eighteenth month of outpatient follow-up, there was no clinical complaint and two urocultures for mycobacteria were negative.


A 53-year-old male with chronic myeloid leukemia (CML), who failed to respond to imatinib (tyrosine kinase inhibitor), underwent allogeneic HSCT for lymphoid blast transformation eighteen months after his initial presentation. Following lymphoid blast transformation, imatinib was also switched to nilotinib (tyrosine kinase inhibitor). The allogeneic HSCT was performed using a conditioning regimen consisting of fludarabine, busulphan and anti-thymocyte globulin (ATG) with ciclosporin A as GvHD prophylaxis. An unrelated male donor matched for HLA A, B, C, and DR loci was used (). Neither donor nor patient had the HLA-DRB1*15:01 genotype associated with increased risk of MS (). Engraftment of neutrophils and platelets occurred promptly, but the patient had routine transplant related toxicities, including post-transplant cytomegalovirus (CMV) reactivation and possible posterior reversible encephalopathy syndrome for which GvHD prophylaxis was switched from ciclosporin A to tacrolimus. There were no changes suggestive of demyelination on brain magnetic resonance imaging (MRI). Tacrolimus was successfully weaned off without GvHD. In view of the high relapse risk, he was maintained on nilotinib post-transplant. Subsequent bone marrow examinations along with peripheral blood monitoring showed full donor chimerism and molecular negativity for BCR-ABL transcripts confirming ongoing molecular remission of leukemia consistent with cure.
Despite a good initial recovery, 10 months later the patient was admitted with confusion, slurred speech, left sided facial weakness, and ataxia (). He had no systemic features suggestive of GvHD, such as rash, deranged liver function, or gastrointestinal disturbance. A brain MRI showed contrast enhancing tumefactive lesions in the left peri-insular area, both corona radiatae and brainstem (). Screenings for human immunodeficiency virus (HIV), Borrelia burgdorferi, syphilis and toxoplasmosis in serum were negative. Analysis of the cerebrospinal fluid (CSF) showed a white cell count of 3 × 106 /L with marginally elevated protein of 0.76 g/L and normal CSF to serum glucose ratio. He had matching bands in CSF and serum (type 4). Screenings for herpes simplex virus (type 1, 2, 6, and 7), varicella zoster virus, adenovirus, enteroviruses, Epstein-Barr virus (EBV), CMV and John Cunningham (JC) virus in CSF were negative. Immunophenotyping of CSF cells and a computed tomography (CT) scan of thorax, abdomen and pelvis did not detect any new or recurrent malignancy. Autoantibody screening for connective tissue diseases and systemic vasculitis were negative.
The patient underwent a brain biopsy, which showed a heavy infiltration of macrophages (CD68-positive), with isolated T (CD3-positive), and B (CD79a-positive) lymphocytes. A luxol fast blue stain revealed severe myelin loss whilst immunohistochemistry to neurofilament protein revealed preserved axons, although some were showing damage and swellings. Reactive astrocytes were present. There was no frank necrosis. Apoptotic cells were not conspicuous and there was no neoplastic infiltration. Special stains for bacteria and fungi were negative, as was immunohistochemistry for JC virus (SV40 antigen). The biopsy findings of a macrophage rich lesion with severe myelin loss but relative axonal preservation suggested a demyelinating pathology (). Culture, 16s rRNA gene detection test, screening for pan-fungal and Aspergillus sp. were negative in the biopsy sample.
In the absence of systemic features suggesting GvHD, infections and relapse of CML, his clinical presentation and investigation results were considered to be in keeping with possible ADEM. He was treated with a 3-day course of intravenous methylprednisolone followed by tapering doses of oral prednisolone. His neurological symptoms gradually resolved, and he was walking 3−5 miles daily without assistance.
Six months later, he was re-admitted with a 3-week history of paraesthesia and weakness of lower limbs and urinary retention. A brain MRI revealed a new enhancing lesion in the occipital horn adjacent to the left lateral ventricle and a spine MRI showed a contrast enhancing lesion in the thoracic cord extending to the conus (). Similar to previous lumbar puncture results, CSF analysis showed mildly elevated protein with matching bands in CSF and serum. Neuromyelitis optica (NMO) antibody in serum was negative. He was treated with another course of intravenous methylprednisolone and a tapering dose of oral prednisolone. He made a full recovery within several weeks and continued to walk 3–5 miles a day. An enquiry to the donor registry confirmed that the donor remained fit and healthy without neurological or autoimmune diseases.
This case therefore posed a unique diagnostic challenge of differentiating between CNS demyelinating disorders and “pure” CNS GvHD. This presentation neither fulfilled the international consensus diagnostic criteria for NMO spectrum disorder nor the Grauer et al. criteria for the CNS manifestations of GvHD due to the lack of systemic involvement (, ). The relapsing remitting disease course was unlikely to be caused by fludarabine or nilotinib toxicity. As the clinical and radiological presentations together with brain biopsy results were thought to be more compatible with relapsing remitting MS, he was commenced on glatiramer acetate and continued on oral prednisolone 5 mg daily.
Two months later, he had another episode of severe myelitis, which was treated with a further course of intravenous methylprednisolone. As the CSF was negative for JC virus, glatiramer acetate was switched to natalizumab, but his disability did not improve and his expanded disability status scale (EDSS) score remained 8.0.
The patient continued to deteriorate requiring another admission with left sided facial and arm weakness five months after starting natalizumab. In view of the diagnostic uncertainty the patient was continued to be investigated for an alternative diagnosis. A spine MRI showed an enhancing lesion in the cervical cord. A third lumbar puncture did not show any new changes and JC virus in CSF remained negative. He was treated with another course of intravenous methylprednisolone. Over the ensuing 15 months, serial MRI scans identified multiple new enhancing lesions in the brain and spinal cord. Visual evoked potentials did not show any evidence of optic nerve involvement on two separate occasions. NMO and myelin oligodendrocyte glycoprotein (MOG) antibodies in serum remained negative.
As he had highly active disease clinically and radiologically despite treatment with a high efficacy DMT, autologous HSCT was considered. As his hematopoietic system was entirely derived from the matched unrelated donor used for the allogeneic HSCT, this was a “domino” autologous HSCT where the patient, a recipient of the previous allogeneic transplant, served as a “donor” for his second transplant. Natalizumab was discontinued and his peripheral blood hematopoietic stem cells were mobilized with cyclophosphamide 2 g/m2 and granulocyte-colony stimulating factor. This admission was complicated by confusion secondary to hyponatremia and a urinary tract infection from which he fully recovered.
A cautious approach was adopted, with a decision to observe the neurological response following cyclophosphamide-primed stem cells mobilization, before pursuing with the “domino” autologous HSCT. However, the patient was re-admitted with dysarthria and dysphagia three months later and a brain MRI showed four new enhancing lesions. A decision was therefore made to proceed with the “domino” autologous HSCT following immunoablation with cyclophosphamide and ATG. Similar to the first transplant, the engraftment of neutrophils and platelets occurred promptly. He had routine transplant related toxicities and also made an unhindered recovery following discharge from hospital. Nilotinib was discontinued after the transplant. Three months later his EDSS score was 7.0.
Twelve months after the transplant, he was admitted with confusion, swallowing difficulties and aspiration pneumonia. A brain MRI revealed new enhancing lesions in the left occipital lobe. He was re-investigated for opportunistic infections and malignancies. Sputum culture, throat swabs, galactomannan, and β-d-glucan tests, multiple blood cultures and viral screenings for HIV, hepatitis B and C, syphilis, toxoplasmosis and cryptococcus were negative. Autoimmune screening for connective tissue disease and vasculitis were also negative. A lumbar puncture showed CSF protein of 0.99 g/L and white cell count of 56 × 106 /L with lymphocytosis. CSF to serum glucose ratio was normal. CSF culture and screening for JC virus, EBV, CMV, toxoplasmosis, Cryptococcus, and acid-fast bacilli were negative. On this occasion, there were matching bands in serum and CSF as well as additional monoclonal bands. Neither immunophenotyping of cells in CSF nor CT scan of chest, abdomen and pelvis showed any evidence of recurrence or new malignancy. A second brain biopsy was offered but declined by the patient.
Over the next ten months, he had several brain and spine MRIs, which continued to show radiologically active disease with new T2 lesions and contrast enhancements. He continued oral prednisolone 5 mg daily. He was started on ocrelizumab but died of progressive disease four months later.
The patient underwent a post-mortem limited to the examination of the brain which weighed 1,208 g and was examined after fixation. Coronal slices of the brain revealed multifocal, irregular white matter lesions in frontal, temporal, and occipital lobes, measuring up to 30 mm in diameter. The lesions had a yellowish granular appearance with a tendency to cavitation. Subcortical arcuate (U-) fibers were not spared. These lesions did not have the appearance of classical MS plaques. In places lesions were sharply circumscribed but elsewhere had more diffuse margins. Myelin stains demonstrated virtually total myelin loss and neurofilament immunohistochemistry showed severe axonal loss with a few remained axonal threads at the lesion margins in contrast to the biopsy. Beta amyloid precursor proteins was upregulated in axons and pyramidal cells at the lesion margins. Ameboid macrophages were highlighted by CD68, particularly in a perivascular location but immunohistochemistry to CD3 and CD20 did not reveal T or B cell infiltration. Occasional vessels showed perivascular sclerosis, but immunohistochemistry to smooth muscle actin showed preservation of vascular media suggesting that there was not a vasculopathy process. S100 labeled small round nuclei in the lesions, suggesting some preservation of oligodendrocytes. No oligodendroglial inclusions were seen and immunohistochemistry for JC virus (SV40 antigen) was negative, as were stains for bacteria and fungi. Focal brown pigment was present, staining with both the Perl's and Masson Fontana methods, suggesting that haemosiderin and some melanin was present. The findings were of a multifocal leukoencephalopathy, with severe loss of both axons and myelin ().


A 56-year-old female with a past medical history of asthma and dyslipidemia presented to a community ED with one week of fever, non-productive cough, dyspnea, headache, nausea and vomiting. She denied smoking history or drug use. Travel history was significant for returning home from an amusement park in Los Angeles one week prior to onset of symptoms. Vital signs at triage were temperature (oral) 38.6° Celsius; heart rate 117 beats per minute; respiratory rate 20 breaths per minute; and pulse oximetry 93% on room air.
Significant laboratory results were as follows: rapid influenza diagnostic test was negative; white blood cells 11.7 10*3 per microliter (mcL) (reference range 4.5–11.5 10*3/mcL), neutrophils relative 92% (reference 50–70%), lymphocyte absolute 0.55 10*3/mcL (reference 0.8–4.80 10*3 /mcL), and lactic acid was 1.0 millimoles per L (reference 0.5–2.2 mmol). A two-view chest radiograph (CXR) was interpreted by the radiologist as pneumonia of the left lower lobe with interstitial changes (). After symptomatic therapy and a first dose of azithromycin, the patient was discharged home with instructions to continue antibiotic therapy and return for worsening symptoms.
Approximately 12 hours after discharge the patient returned to the same ED with worsening dyspnea. Upon arrival she was noted to be ill appearing, tachypneic and with moderate respiratory distress despite similar triage vital signs as the initial ED visit. Her lung exam was significant for poor inspiratory effort and rhonchi at the bases. A multi-organ POCUS exam was performed to determine the cause of the patient’s dyspnea.
A cardiac parasternal long-axis view demonstrated normal systolic ejection fraction and no pericardial effusion (). The IVC in the subxiphoid view showed greater than 50% collapse during inspiration (). A lung exam using a low frequency (5–2 megahertz) curvilinear transducer in the anterior, lateral, and posterior portions, showed the presence of diffuse scattered B-lines with small subpleural consolidations and effusions in each lung zone, with confluent B-lines in the posterior inferior lobes bilaterally (). POCUS findings were interpreted as the presence of a non-cardiogenic multifocal interstitial lung process with COVID-19 being high on the differential. The patient was placed in a negative pressure room, and all staff were informed to wear full personal protective equipment when interacting with the patient.
Based on the POCUS multi-organ findings, the patient was resuscitated with an intravenous bolus normal saline and treated with broad-spectrum antibiotics (levofloxacin). SARS-CoV-2 oropharyngeal and nasopharyngeal swabs were sent from the ED for testing. The infectious disease consultant agreed with a plan for admission and continuation of droplet, airborne, and contact precautions given the progression of symptoms and worsening respiratory status. She was admitted to a negative pressure room on the medical floor for continued therapy and monitoring of respiratory status. An eventual non-contrast CT of the chest demonstrated diffuse multifocal infiltrates ().
As an inpatient, the patient’s antibiotic regimen was adjusted to doxycycline and cefepime. She was under observation and isolation for six days at the hospital of presentation. At this point the SARS-CoV-2 testing had not yet resulted, but her clinical course had improved. She was discharged home with instructions to self-quarantine at home or return to the ED if symptoms worsened. SARS-CoV-2 testing resulted the day after discharge as positive for SARS-CoV-2 ribonucleic acid.


A 58-year-old female patient was admitted to our hospital in September, 2018. But the history of breast related diseases started eight years ago. In October 2010, the patient had a painless mass about 0. 5 cm in the upper quadrant of the right breast. Standard mammography examination indicated cystic changes in double breast and nodules in the right breast. The patient underwent a minimally invasive resection of the tumor. Postoperative pathology indicated breast hyperplasia and fibroadenoma. In July 2012, the patient's right breast mass recurred. Right breast mass resection was performed again, and the postoperative pathology was still fibroadenoma of breast.
The recurrence of the right breast mass occurred in June 2013. At that time, the size of the tumor was about 1 × 1 cm, but the patient chose not to have surgery. Five years later, in September 2018, the mass of the right breast increased to about 15 × 10 cm. The pain in the right breast was obvious. The volume of the right breast increased significantly, with high skin tension, local redness and obvious tenderness, occupying most of the breast. Magnetic resonance examination of the breast suggested space-occupying lesions in the right breast, which was considered as breast cancer [BI-RADS category 5] with enlarged lymph nodes in the right axilla (Fig. ). The patient underwent right breast mass biopsy under ultrasound guidance. Postoperative pathology indicated a right breast phyllodes tumor. Then, the patient underwent surgical treatment, and the surgery was as follows: right breast phyllodes tumor expanded resection + axillary lymph node dissection + free DIEP skin flap repair + fibrous vascular anastomosis×4 +umbilical angioplasty. The histopathologic findings: a right breast malignant phyllodes tumor with chondrosarcomas and osteosarcomas in some areas. No tumor was found in the nipple, incised line and marked incised margin. Immunohistochemistry: CK-,CKT-,Vimentin+. No metastatic tumor was found in the right axillary lymph node (0/27).
The patient rested for 2 months after surgery. Then the patient was found to have a 1 × 1 cm nodule in the surgical scar on the right chest wall. The skin at the nodule is reddened without tenderness. Computed tomography (CT) imaging of the chest revealed a small tissue density mass in the right chest wall (Fig. ). The pathological results of nodular puncture showed malignant tumor, which tended to be phyllodes tumor. The oncologist gave radiotherapy to the right chest with the recurrent nodule. The prescription dose was PTV 60Gy/30 fractions. Because of the patient refused chemotherapy, she was treated with apatinib. The apatinib dose applied was 0. 5 g per day continuously.
Half month after radiotherapy, the patient presented lumbosacral pain. PET-CT showed that the patient had multiple bones metastasis (Fig. A). The retraction of the tumor in the radiotherapy area was not obvious (Fig. B). Oncologists recommend systemic chemotherapy and radiation therapy for metastatic lesions. The patient refused other treatments and continued to take apatinib. A month later (in March 2019), the patient had frequent seizures at home, combined with headache and mental disorder. In the end, we speculated that she died of brain metastases, brain hernia.


A 59-year-old female patient was admitted because of jaundice and general weakness. On the computed tomography (CT) scan, a pancreatic head mass with lung nodules was detected (Fig. A and B). The initial laboratory findings were as follows: aspartate aminotransferase level, 275 IU/L; alanine aminotransferase level, 413 IU/L; total bilirubin level, 14.9 mg/dL; and direct bilirubin level, 8.7 mg/dL. The mass was confirmed to be pancreatic adenocarcinoma by endoscopic ultrasonographic fine-needle aspiration. Multiple hypermetabolic lesions were found not only in the pancreatic head but also in the lung, pelvic cavity, and peripancreatic area on positron emission tomography-CT (Fig. C). Biliary stenting was performed using a metal stent (uncovered metal stent, 7 cm; Mitech Co Ltd, Seoul, South Korea) into the bile duct. After metal stenting, the total bilirubin level decreased to <3.0 mg/dL. As her Eastern Cooperative Oncology Group performance status score was 1 to 2, 1st-line chemotherapy was initiated with gemcitabine and nab-paclitaxel. Despite the systemic chemotherapy for 4 months, cancer progression was observed on the follow-up CT scan, and the therapeutic plan was changed to conservative treatment.
During the course of the chemotherapy, she had repeated aggravation of jaundice due to food impaction and stent clogging. Therefore, an antireflux valve stent (8 cm; S&G BioTech Inc, Seoul, South Korea) was inserted after removal of the inner full-covered metal stent. Finally, an external uncovered metal stent with an internal antireflux valve stent was inserted (Fig. ).
She was admitted because of severe abdominal pain and septic condition 1 month after insertion of an antireflux valve stent. A diffuse dilated peripheral bile duct was observed, but no filling defect was found in the common bile duct and metal stent. In the endoscopic view of duodenoscopy, a hardened and tightly stuck antireflux valve was found (Fig. ).
The flexible liner tip was firmly obstructing the reflux tip with deformity, making intraluminal cannulation through the stent impossible. Therefore, forceps were used to roughly tear the stent, and bile juice gushed out after partial tearing of the hardened portion of the stent (see Supplemental Video 1; Forceps were used to roughly tear the hardened stent opening, and congested bile juice gushed out afterwards). Then, the antireflux valve stent was extracted using a snare basket (Fig. ). Instead of another metal stent, 2 double pigtail stents were inserted through the firstly inserted metal stent to prevent food impaction.
Six weeks later, a partially covered metal stent (9 cm; BONASTENT, Standard Sci Tech Inc, Seoul, South Korea) replaced the plastic pigtail stents after confirming these stents being clogged by endoscopic retrograde cholangiography. Hyperbilirubimenia was improved (total bilirubin 8.96 → 7.53) after the change of stents. Unfortunately, the patient died 1 week later due to acute respiratory distress syndrome.
Informed consent was obtained from the patient for the purpose of publication.


This 46-year-old male underwent a superficial parotidectomy following presentation to
our unit with a right parotid lump. He was previously fit and well with no family
history of note. Histology confirmed a pT1 pN0 M0 ACC with risk factors including R1
resection at the deep margin and perineural invasion for which he completed adjuvant
radiotherapy (60 Gy in 30 fractions) in February 2016. Post treatment magnetic
resonance imaging (MRI) of his neck 3 months later showed no residual or recurrent
disease, and he continued with standard 3 monthly clinical follow-up in the ENT
(ear-nose-throat) clinic.
In April 2018, he complained of 3 episodes of headache, associated with temporary
visual changes in his right eye, thought to be migraines. At follow-up 3 months
later, he was noted to have tanned skin despite little sun exposure. Metabolic
changes such as weight gain, hyperglycemia, or hypertension were not noted. He was
referred via his general practitioner to a consultant gastroenterologist for
investigation of hemochromatosis. By August 2018, he was reporting increased
fatigue, had developed multiple subcutaneous nodules, and attended our emergency
department with a focal seizure in his left arm, reported to follow another episode
of migraine-type headache.
Imaging with computed tomography (CT) confirmed extensive disseminated malignancy
with nodal, pleural, peritoneal, liver, and renal metastases (). An MRI of head and whole spine
showed metastases in the right frontal lobe and bilateral parietal lobes, a deposit
along the L4 nerve root, as well as bone metastases throughout his cervical,
thoracic, and lumbar spine. There was no evidence of locoregional relapse.
Biopsy from a supraclavicular fossa node showed poorly differentiated carcinoma
infiltrating within fat (). Immunostaining for α1-antichymotrypsin, a marker commonly expressed
in ACC, was positive. Review of the previous histology from the right parotidectomy
showed an ACC, mostly showing a microcystic pattern but with more poorly
differentiated areas with higher proliferation, resembling the metastatic lesion
from 2018. Again, expression of α1-antichymotrypsin was demonstrated on
immunostaining. It was concluded that the supraclavicular fossa lesion represented
metastatic ACC. Subsequent immunostaining of the original tumor showed focal
expression of ACTH within scattered tumor cells, consistent with the clinical
picture of increased skin pigmentation. The nodal biopsy was too small to perform
ACTH staining on. No genetic studies were done on the tumor.
On examination, he had Cushingoid fat distribution, hyperpigmentation, signs of
agitation, proximal weakness, and hypokalemia at 2.5 mmol/L. An early morning
cortisol level was markedly high at 1619 nmol/L in keeping with Cushing’s syndrome.
In view of the very high cortisol level and significant symptoms, our endocrinology
team did not want to delay starting treatment. Consequently, other tests, such as a
dexamethasone suppression test, were not performed at this time. He was started on a
block and replace regimen of metyrapone and dexamethasone the same day, with a view
switching to hydrocortisone pending response to chemotherapy. The MRI of head had
shown unremarkable appearances of the anterior and posterior pituitary. Ectopic ACTH
secretion was the likely underlying cause.
He commenced palliative chemotherapy with carboplatin and paclitaxel. In addition, he
had a single 8 Gy fraction of palliative radiotherapy to his lumbar spine for
pain.
Despite chemotherapy, he deteriorated with increasing generalized edema, back pain,
and restrictions in mobility along with development of distal weakness in his right
upper limb. His cortisol levels improved to 558 nmol/L, and his potassium normalized
at 3.7 mmol/L. Repeat imaging after 3 cycles confirmed progressive disease in his
liver and extensively throughout the spine along with a new metastatic deposit on
the left adrenal gland. His nodal and intracranial disease was stable, and there was
some regression in the right renal metastasis. By this point, his performance status
had fallen to World Health Organization 3, and a decision was made with the patient
to stop chemotherapy and focus on symptomatic care.


A 35-year-old female complained of pain and instability in right knee following twisting injury a year back. Clinical examination revealed positive Lachman, grade I pivot shift, and grade II anterior drawer. Her knee range of motion (ROM) was near full with a positive patellar apprehension on the affected side. Beighton score was normal.
MRI evidence showed complete ACL tear and MPFL tear from femoral attachment. She underwent arthroscopic ACL along with open MPFL reconstruction.


A 39-year-old female presented to outpatient department with pain and instability in right knee following slip and fall two weeks back. Mechanism of injury was of valgus and external rotation. She had a childhood history of bilateral patellar dislocation. Clinical examination revealed positive Lachman, grade II pivot shift, and grade II anterior drawer. Her knee ROM was full with a positive patellar apprehension on the affected side. Beighton score was normal.
Plain radiographs were normal. MRI evidence showed complete ACL tear and MPFL tear from femoral attachment. CT scans of both lower limbs revealed normal bony alignment and tibial tuberosity trochlear groove (TTTG) distance. We went ahead with arthroscopic ACL along with MPFL reconstruction.


A 28-year-old female came with complaints of left knee pain and instability following valgus injury while dancing three weeks back. Since then she had experienced four episodes of patellar dislocation. Clinical examination revealed positive Lachman, grade II pivot shift, and grade III anterior drawer. She had a positive patellar apprehension test with terminal restriction of knee ROM. We arrived at a clinical diagnosis of ACL and MPFL insufficiency. Beighton score was normal.
Plain radiographs were normal. MRI evidence revealed complete ACL tear from femoral attachment (Figure ). However, MPFL was normal and no classical contusion pattern was also seen (Figure ). CT scans showed normal TTTG and bony alignment with patellar maltracking (Figure ). In view of recent episodes of recurrent patellar instability, positive patellar apprehension, and patellar maltracking we went ahead with MPFL reconstruction along with ACL reconstruction.
Surgical technique
Under spinal anesthesia, examination under anesthesia (EUA) was done to confirm positive Lachman, pivot shift, and lateral patellar translation. The patient was positioned supine on operating table with lateral thigh and foot post. Pneumatic tourniquet was applied to both the thighs.
Semitendinosus (ST) graft and gracilis graft were harvested from ipsilateral leg. Gracilis graft was prepared to reconstruct MPFL. If the harvested ST graft is of inadequate dimensions for ACL reconstruction, then contralateral hamstring was used. Through standard anterolateral and anteromedial portals, ACL tear was visualized (Figure ). Femoral and tibial tunnels for ACL reconstruction were made.
For MPFL reconstruction, patellar fixation of graft was done using two tunnel transosseus suture loop technique with the graft secured medially over the patella without going through patellar tunnels (Figure ,B). The graft was then passed between layer 2 and layer 3 of medial aspect of knee and isometric fixation to the femur was done using an interference screw (Figure ). Patella was found to be centrally tracking after reconstruction. Following MPFL fixation, prepared ST graft was passed through femoral and tibial tunnels and fixed using suspensory button proximally and interference screw distally to reconstruct ACL. Postoperative radiographs were taken to confirm proper tunnel placement (Figure ,C). Patients were made to partial weight bear for the first three weeks.
Follow-up
Rehabilitation protocol was different from isolated ACL reconstruction in that ROM was started after week 1. Patient 1 and patient 2 had restricted knee ROM postoperatively. However, with continued rehabilitation, ROM improved and the patients regained full range at one-year follow-up. Both have returned to preinjury activity level at one-year follow-up. They had no episodes of instability at five years follow-up with satisfactory Kujala and IKDC knee scores.
In view of knee stiffness in the initial three weeks with patients 1 and 2, we started immediate aggressive ROM rehab for patient 3. She did not experience any difficulty and regained full range at 2 months follow-up.


Our subject was an 8-year-old girl born at 36 weeks’ gestation and the first child of healthy non-consanguineous French parents. Family history was unremarkable. She has one healthy younger brother. Her birth weight was 2200 g. Newborn hearing screening was not performed at birth. Developmental milestones were normal with walking at the age of 16 months and first words at 12 months. At the age of 4 years, she started to present difficulties at nursery school that led to hearing screening. A bilateral severe sensorineural hearing loss was finally identified at the age of 7 years. Tonal audiograms (Fig. ) did not show the upsloping pattern considered as typical for HARS2 mutations and described in one case of a LARS2 mutation []. Hearing loss was severe on both sides with a discreet U-shaped curve centered on the 1000 Hz frequency. Transient otoacoustic emission and distortion product otoacoustic emission of both ears were absent. Auditory evoked potentials showed recognized curves at 80 dB on both sides and confirmed severe hearing loss. A temporal bone computed tomography scan and magnetic resonance imaging (MRI) performed to exclude other inner ear malformations were normal.
At the age of 7 years, she received a cochlear implant on the right side (CI-522 cochlear) and responded well. One year later, the tonal free field audiogram showed 25 dB hearing levels on conversational frequencies and the vocal audiogram showed 100% of comprehension at 60 dB (intensity of normal voice). She had no neurological symptoms and her cognitive development was normal. At physical examination, she exhibited normal growth parameters and no dysmorphic features. She had astigmatism and three small café-au-lait macules. At the age of 8 years and 7 months, an endocrinological workup showed a chronological bone age that predicted a normal adult height. Hormonal assessments showed normal prepubertal values of follicle-stimulating hormone (FSH) (2.8 IU/L) and luteinizing hormone (LH) (0.7 U/L). Estradiol was below the detection limit of 17 pmol/l. Inhibin B was undetectable and the anti-Mullerian hormone (AMH) was 1.0 pmol/l. A pelvic ultrasound showed a normal prepubertal uterus measuring 32 mm in length. A right ovary measuring 16 × 6 × 6 × 6.5 mm was visualized. The left ovary was not clearly visualized. Thyroid function, insulin-like growth factor 1 and morning cortisol values (275 nmol/l) were normal. Glucose metabolism was normal with fasting blood glucose values of 4.7 mmol/l, insulin, 3.3 mIU/l, and glycated haemoglobin, 5.0% (31.0 mmol/mol).
Written informed consent from the parents was obtained prior to molecular studies and whole-exome sequencing was performed. Exome of the patient was captured using the SureSelet QXT Human All Exon V5 kit (Agilent Technologies Inc., Santa Clara, CA, USA) and sequenced on a NextSeq500 instrument (Illumina, San Diego, CA, USA).
Reads mapping and variant calling were performed using BWA 0.7.13, Picard 2.9.0 and GATK HaplotypeCaller 3.7 and annotated with annovar 2017-07-17 and UCSC RefSeq (refGene) downloaded on 2018-08-10. The variants were searched for in various databases including dbSNP151, gnomAD 2.1, ClinVar 2018 and HGMD 2016.
Pathogenicity prediction scores were obtained for missense variants using SIFT, PolyPhen, MutationTaster and CADD. Splicing effect alterations were assessed using dbscSNV.
Our patient was found to carry two missense variants in the LARS2 gene (NM_015340.3.3): c.457A > C, p.(Asn153His) in exon 6 rs786205560, and c.1565C > A, p.(Thr522Asn) in exon 14, rs199589947. Segregation analysis showed that the patient inherited the p.(Asn153His) variant from her father and p.(Thr522Asn) from her mother, consistent with an autosomal recessive mode of inheritance.
The c.457A > C, p.(Asn153His) variant is absent from the gnomAD database and has been classified once in ClinVar as “likely pathogenic” and once as “of uncertain clinical significance”. The amino acid change was predicted as pathogenic by all used algorithms. As the c.457A > C variant changed the second nucleotide of exon 6, it could therefore have affected splicing, as predicted by the dbscSNV (score = 0.93) and recently reported in homozygosity by Al-Jaroudi et al. [] The c.1565C > A, p.(Thr522Asn) variant is present in the gnomAD database (MAF = 2.8 × 10− 4) at a frequency compatible with a recessive mode of inheritance. It is also predicted as pathogenic by all used algorithms and is classified three times as “pathogenic” and once as “likely pathogenic” in ClinVar. It has already been reported in the literature as associated with Perrault syndrome [, ]. According to the ACMG guidelines [, ], we classified the p.(Asn153His) and p.(Thr522Asn) variants as pathogenic. The presence of these two variants in compound heterozygosity indicated that our patient presented a Perrault syndrome.


A 34-year-old man was hospitalized for preemptive living KT. He was diagnosed with end-stage renal disease secondary to IgA nephropathy 1 year prior. He underwent ABO-incompatible living KT. The donor was his brother, and his right kidney was selected for allograft because the 99 m-Tc-diethylenetriamine pentaacetic acid renogram revealed that the glomerular filtration rate of the right kidney was > 10% of that of the left kidney. The allograft had three renal arteries (Fig. a, b) and four renal veins (Fig. c, d). The renal arteries and veins were cut at the dotted line shown in Fig. b and d. The donor’s gonadal vein was harvested for vascular graft because of vascular complexity. The diameter of gonadal vein was approximately 3 mm. The renal arteries and veins were trimmed and prepared on the back table, as shown in Fig. a, b, and c. The renal arteries were reconstructed into one piece using the internal iliac artery graft obtained from the recipient by interrupted 7/0 Proline stitches. The two arteries, both had a diameter approximately 5 mm, at the middle of the renal hilum were reconstructed into one piece using the conjoined method by interrupted 7/0 Proline stitches. The superior renal artery was too short to anastomose to the internal iliac artery graft. The inferior epigastric artery was insufficient for anastomosis to the renal artery or interposition. The diameter of inferior epigastric artery was approximately 1 mm, compared to that of superior renal artery was approximately 3 mm. Although an interposition method using an artificial blood vessel graft was also considered, we decided to use the gonadal vein graft obtained from the donor for long-term patency of the graft. The superior renal artery was lengthened using the donor’s gonadal vein and subsequently anastomosed to the internal iliac artery graft (Fig. d). The internal iliac graft was anastomosed to the original internal iliac artery (Fig. e) using 6/0 Proline suture in an interrupted fashion. The renal veins were anastomosed to the external iliac vein and the recipient’s gonadal vein (Fig. f). Intraoperative Doppler ultrasonography (US) revealed that the blood flow in each renal artery was adequate, resulting in sufficient blood flow throughout the allograft. Urine output was observed immediately after the blood flow returned. Doppler US showed no evidence of anastomotic stenosis, obstruction, or aneurysm of the renal arteries on postoperative day (POD) 10 (Fig. a), 17, 24. There were no surgical complications, and the patient was discharged on POD 32. The renal arteries and allograft were evaluated annually by Doppler US (Fig. b, c, and d). The renal graft function has been maintained with a serum creatinine level of approximately 0.9 mg/dL, and there was no evidence of vascular complications on Doppler US performed 3 years after KT.


A 37-year-old Japanese man had his right eye hit by a fist in an accident. He felt visual impairment in his right eye and was transferred to the emergency unit of Chiba University Hospital. His visual acuity was 20/200 in the right eye and 20/16 in the left eye at the initial presentation. The refractive error of spherical equivalent was −12.0 diopters in his right eye and −4.0 diopters in his left eye. He had a laceration of the lower eyelid, hyphema, and angle recession for 180 degrees and commotio retinae. The ultrasound biomicroscopy presented a cyclodialysis cleft in the nasal half. The intraocular pressure was 5 mmHg in the right eye and 15 mmHg in the left eye. He started topical steroids and atropine. Although the inflammation gradually decreased, the IOP in the right eye remained at a low level. There were significant findings of hypotony maculopathy with retinal and choroidal folds at macular, and his visual acuity was 20/50 (). At 11 months after the trauma, his visual acuity decreased to 20/200 because of the progression of cataract concomitant with maculopathy. He underwent phacoemulsification and aspiration, implantation of the intraocular lens, and encircling with a 7 mm width silicone tire to increase IOP by blocking the suprachoroidal outflow. There was no complication during the surgery. His visual acuity improved to 20/20 with a refractive error of −6.0 diopters at one month after the surgery. The intraocular pressure in his right eye increased to 12 mmHg, and the retinal and choroidal folds were completely resolved at 3 months postoperatively (). The visual acuity and intraocular pressure were stable for 7 years after the surgery.


A 4-year-old girl was noted to have CSP without intellectual disability, and she seemed to have a short palate and a deep pharynx. On assessment using the University of Pittsburgh weighted values for speech symptoms associated with VPI, her speech outcome was: nasal emission, 5/5; facial grimace, no; hypernasality, 3/4; phonation, N.A; and articulation, 6/10 [,]. NPS and LPG were performed preoperatively to evaluate the movement of the soft palate and the lateral wall of the pharynx, as well as the anatomical structure of the palatopharynx. There was no contact between the posterior pharynx and soft palate during phonation, and a large defect was seen on NSP (). Furthermore, her soft palate length was classified as Randall classification type III at the beginning of the operation []. As for intraoperative findings, her LVPM continued from side to side completely, as in the normal anatomy, and the anterior portion was attached to the posterior border of the hard palate (). Therefore, Furlow’s palatoplasty and intravelar veloplasty, which separate the LVPM from the nasal mucosa, were not performed to maintain the continuity of the LVPM, and for the first operation, a right BMMF (35 mm × 12 mm), of which the pedicle was denuded, was performed for soft palate elongation on the nasal side, along with Z-plasty without LVPM separation on the oral side ( and ). The operative time was 3 h, and the hospital stay was 8 days. After the first operation, her speech outcome improved from severe to moderate, but her VPI remained. For the second operation, oral mucosal flaps were raised because the soft palate already had scar formation from the previous Z-plasty, and the LVPM remained without separation again, because the LVPM was confirmed to be completely continuous. Therefore, a left BMMF (35 mm × 12 mm) for soft palate elongation on the nasal side was performed again, and a skin graft, taken from her groin on the oral side, was performed for the defect of the hard palate ( and ). The defect of the nasal surface was closed during phonation on NPS after the second operation. She was fed through a gastric tube for 7 days to prevent misalignment of the dressing on the graft due to food in the mouth, and over the next 7 days, the food was changed from a light diet to a regular diet. Her postoperative speech outcome improved (nasal emission, 0/5; facial grimace, no; nasality, 0/4; phonation, 0/3; and articulation, 0/10) after two operations. There was also no space between the posterior pharynx and the soft palate during phonation on LPG (, ).


We present the case of a 67-year-old Caucasian female with prior tobacco use, essential hypertension, hyperlipidemia, coronary artery disease, status post (s/p) remote percutaneous coronary intervention (PCI) to the right coronary artery who presented to the hospital with complaints of chest discomfort and shortness of breath. The patient was found to have acute lateral ST segment elevations on the presenting electrocardiogram (EKG) (Figure ). The patient was treated for acute coronary syndrome and urgently taken to the cardiac catheterization laboratory where she underwent left heart cardiac catheterization and coronary angiography. Angiogram revealed the previously placed mid right coronary artery stent to be widely patent. The left circumflex and main left anterior descending arteries showed minimal luminal irregularities. However, the second diagonal branch of the left anterior descending artery did reveal a dissection plane (Figure ). Due to small caliber vessel, no further intervention was attempted. The coronary angiogram was followed by ventriculography which revealed a typical TCM pattern of the left ventricle with hyperkinesis of the basal segments and akinesis/ballooning of the mid and apical segments (Video ). The patient was managed medically for SCAD and given guideline directed medical therapy for stress induced cardiomyopathy.


The patient was a 57-year-old female who had been diagnosed with FD in 2007, confirmed by genetic tests that detected an abnormality of the GLA gene with the p.R342Q variant. She was a smoker, had systemic arterial hypertension, and was free from renal and cardiac complications. She had hyperhidrosis, hypoacusia, and angiokeratoma on the hands. She stated that she had had no other symptoms during the course of the disease. Her surgical history included three caesarean deliveries, varicose veins surgery, blepharoplasty, lipoaspiration, and mamoplasty. She was one of nine siblings, five of whom had been diagnosed with the disease (two males and three females), including the patient. Her mother, who had not been diagnosed, and both brothers suffered renal failure around the fourth decade of life. The patient had had an ischemic stroke episode at 40 years of age, without sequelae. Two years previously, she had complained of onset of pain at rest in the right lower limb, had undergone angiography of the limb and had been treated with percutaneous transluminal angioplasty with placement of a Supera Abbott® stent in the right superficial femoral artery (SFA), which was a technical success and resulted in resolution of the pain. The patient was put on double platelet antiaggregation with 100 mg acetylsalicylic acid (ASA) and 75mg clopidogrel and control color Doppler ultrasonography (CDUS) was conducted at 3-month intervals, showing that the stent was patent until, at 9 months of follow-up, the patient began to complain of intermittent claudication of the right lower limb after walking 50 meters. Angiotomography was conducted, showing the stent was patent, but revealing critical stenosis of the distal right popliteal artery (). During the second procedure, we only conducted angioplasty with a Freeway Eurocor® drug-eluting balloon, with excellent results (
). After the procedure, we put the patient on 20 mg/day rivaroxaban and 100 mg/day ASA. After 12 months of follow-up after the second intervention, the patient presented with acute pain and paresthesia in the right leg and foot. She underwent urgent arteriography, which showed proximal occlusion of the right SFA (). A Fountain Merit® catheter was fitted and 50 mg of alteplase was administered by continuous infusion with an infusion pump over 24 hours. After the infusion, the patient was taken to the hemodynamic room for arteriography, which demonstrated complete patency of the SFA and segment 1 of the right popliteal artery () and with 90% stenosis of segment 2 of the right popliteal artery. The decision was taken to deploy another Supera® stent and perform angioplasty, with excellent results and total reperfusion of the arterial tree (
). Rivaroxaban was reintroduced at 20 mg/day and the patient is in follow-up with CDUS at 3-month intervals. This patient has certain symptoms that are not typical of the disease, such as hyperhidrosis. The thrombotic events are the result of Gb3 deposition in the vascular endothelium, constituting a prothrombotic state that explains the recurrence of symptoms and arterial thrombosis in the lower limb.


A 67-year-old male with a past medical history of asthma and hypertension presented to the emergency room for evaluation of a 5-day history of fever, cough, chest pain, shortness of breath, and body aches (). The patient was seen at an urgent care center and was diagnosed with bronchitis, but his symptoms worsened. He also had a chest X-ray, which indicated pneumonia and was treated with Augmentin and doxycycline. He traveled recently to Aruba, but he denied sick contacts. The initial vitals showed a temperature of 97.9 Fahrenheit, pulse rate of 104 beats per minute, respiratory rate of 20 cycles per minute, blood pressure of 143/91 mmHg, and pulse oximetry of 97% on room air. Physical examination was unremarkable. Initial laboratory showed normal complete blood count but a white blood cell count of 4.1 k/μL, platelets of 121 k/μL, aspartate transaminase of 48 U/L, and alanine transaminase of 92 U/L. Urine was negative for Legionella and Streptococcus pneumoniae antigens. Chest X-ray demonstrated diagonal band-like density in the right upper lobe and linear densities at the bases (). His oronasal swab was positive for SARS-CoV-2. He was started on ceftriaxone and azithromycin before he was transitioned to levofloxacin and hydroxychloroquine.


A 46-year-old male with no significant past medical history presented to the emergency room because of an episode of seizures, cough, fever, vomiting, diarrhea, and syncope (). His symptoms started three days before presentation. His home temperature was 101.6 Fahrenheit, but it resolved with acetaminophen. On the day of presentation, he syncopized, vomited, and had one episode of seizures. He had an involuntary loss of feces, but he regained consciousness after 30 seconds. He also had a similar episode in the emergency room on the same day but for a duration of two minutes. He denied a headache, chest pain, shortness of breath, palpitations, abdominal pain, or runny nose. His initial vital signs revealed a temperature of 99.1 Fahrenheit peaking at 102.9 Fahrenheit the following day, pulse rate of 86 beats per minute, blood pressure of 130/90 mmHg, and pulse oximetry of 95% on two liters of intranasal oxygen. Physical examination was essentially unremarkable. The initial laboratory investigations revealed a normal complete blood cell count but sodium of 131 mmol/L, creatinine of 1.9 mg/dl, aspartate transaminase of 62 U/L, alanine transaminase of 73 U/L, and alkaline phosphatase of 225 U/L. A urine drug screen and urinalysis were insignificant. However, his creatine phosphokinase was elevated at 1427 U/L. A chest X-ray revealed grossly clear lungs. A head CT and MRI were unremarkable. A lumbar puncture for cerebrospinal fluid was temporarily deferred because of the lethality of the disease and its unlikeliness to change the management. Laboratory result was eventually positive for SARS-CoV-2. He was originally treated with vancomycin, ceftriaxone, and acyclovir before they were switched to azithromycin and hydroxychloroquine.


A 43-year-old male with no significant past medical history presented to the emergency room with shortness of breath, cough, fever, chest pain, and headache for about one week (). He was taking doxycycline for pneumonia before presentation; however, his symptoms did not resolve. He denied sick contacts, recent travel, or being in contact with someone who traveled. He also denied vomiting, diarrhea, or abdominal pain. Initial vitals showed a temperature of 98.7 Fahrenheit but rising to 101.2 Fahrenheit, pulse rate of 76 beats per minute, respiratory rate of 18 cycles per minute, blood pressure of 121/75 mmHg, and pulse oximetry of 95% on room air. Physical examination revealed breath sounds that were equal bilaterally. The initial laboratory showed a white blood cell count of 2.1 k/μL, hemoglobin of 12.8 g/dl, and platelets of 110 k/μL, but a complete metabolic panel was normal. Laboratory investigation was also negative for HIV 1 and 2, influenza A and B, and respiratory syncytial virus. A chest X-ray demonstrated mild fullness in the right perihilar region (.). He was diagnosed with COVID-19 and was started on levofloxacin but he received hydroxychloroquine for two days.


Patient 1 was a 28-year-old, gravida 1 para 0 woman whose elective triple marker screen revealed a low risk of trisomy 21/18/13. Nuchal translucency (NT) was 1.3 mm at 13 gestational weeks. However, with the help of prenatal ultrasound series monitoring, a mild echogenic bowel (grade 1) and hydramnios with amniotic fluid volume (AFV) 74 mm were noted at 28 gestational weeks. The patient’s past medical history was significant only for Southeast Asian deletion α0-thalassemia (−-SEA). Two months prior to pregnancy, she started taking 0.4 mg folic acid and calcium tablets. Furthermore, the social history of the patient was negative for alcohol, tobacco, and illicit drug use before/during pregnancy.
NIPT based on low coverage (0.1×) whole-genome sequencing using an Ion Proton Sequencer (CapitalBio Technology Inc., Beijing) was performed at 28 gestational weeks, and it suggested that there was a 1.1 Mb deletion, with a z-score of − 10.76, located at 21q21.1. The estimated fetal DNA concentration in the maternal plasma was 19.7% on analysis (Table and Fig. a). To explore the precise details, umbilical cord blood samples were punctured at 29 gestational weeks for the aCGH analysis. However, the aCGH analysis revealed a 422 kb deletion at 15q13.3, rather than the 21q21.1 deletion (Fig. a).
After extensive counseling, the patient told us that her husband had a history of epilepsy, which made us reconsidered this result. We then collected the peripheral blood of the parents for aCGH analysis. The mother’s blood showed a 1.1 Mb deletion at 21q21.1. The father’s blood showed the same deletion (422 kb deletion) at the region of 15q13.3 (Fig. b and c).
As is routine practice, an ultrasound was conducted to monitor the developmental status of the fetus, and no obvious abnormalities were recorded. The parents decided to continue the pregnancy. A male baby 3160 g and 51 cm high was delivered at term with no phenotypic abnormalities, and the Apgar score was 9 at 5 min. As follow-up, the neonate was normal in growth and psychomotor development at 6 months of age.


A 31-year-old, gravida 6 para 1 woman presented for prenatal counseling at 12 gestational weeks. First-trimester serum screening (FTS) indicated that the fetus was at intermediate risk of trisomy 21 syndrome (1/750) in another hospital. The woman had experienced three spontaneous abortions and one labor induction for intestinal malformation. She asked for NIPT at 13 gestational weeks due to FTS results and abnormal reproductive history. NIPT revealed a 1.5 Mb deletion at 22q11.21, which overlaps the critical region of DiGeorge syndromes. The cffDNA was 14.7%, and the z-score was − 6.71 (Table and Fig. b). Conventional cytogenetic analysis of cultured amniocytes revealed a normal karyotype of 46, XY in all 40 cultured colonies. Then, aCGH was applied to the remaining uncultured amniocytes, and aCGH revealed a 1.377 Mb duplication rather than a 1.5 Mb deletion at 22q (Fig. a). The result of the fetus was arr[hg19] 22q11.21(1935464–20312661)×3. Furthermore, aCGH analysis of the parental blood samples was performed to explore the real origin of the CNVs. It revealed the result of arr[hg19] 22q11.21(20716876–21363447)×1, indicating a 647 kb deletion of 22q11.21 in the mother, and an arr[hg19] 22q11.21(18636749–21461017)×3, indicating a 2.8 Mb duplication of 22q11.21 in the father (Fig. b and c); the area almost overlapped with the CNV of the fetus. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature 2016 (ISCN 2016) criteria []. Continuous prenatal ultrasound monitoring and III level ultrasound screening at 24 gestational weeks did not find remarkable malformations. The location and volume of the fetal thymus and fetal echocardiogram were normal. A male infant with a weight of 2870 g and height of 46 cm was born at 37 + 3 weeks with no phenotypic abnormalities, and the Apgar score was 8 at 5 min.


A 47-year-old man presented with a 2-year history of swelling and accompanying pain in the left wrist, but no paresthesia. Massage and infrared treatment had resulted in no obvious improvement in these symptoms. Ultrasound examination revealed a 4.0 cm × 3.0 cm subcutaneous hypoechoic mass with no blood flow. Physical examination indicated no swelling of the superficial lymph nodes. There was an intumescence at the distal end of the left forearm, with no dark purple skin (Fig. A). On palpation, the local, diffused soft mass had an unclear boundary and normal skin temperature, was nonpulsatile, and did not move in different positions. Tinel sign was negative at the wrist.
Wide-awake technique[ was used for mass resection: a 6-cm arc-shaped incision was made at the ulnar edge of the long palmar muscle of the distal forearm, followed by peeling back the skin and subcutaneous tissues (Fig. B). No subcutaneous edema was observed. There was no obvious inflammation in the deep fascia and sarcolemma. Local intumescence was obvious, and no enclosed mass was felt in the flexor tendons or muscles. Subsequently, the seromuscular layers were exposed, and there was no synovial hyperplasia or other inflammatory changes in the tendon. After moving the flexor tendons, a yellowish-white mass wrapped with muscle fibers was observed on the lunar side of the pronator quadratus (Fig. C). The muscle fibers were bluntly peeled, and a 4.0 cm × 3.0 cm oval, yellowish-white, soft mass with an intact capsule emerged (Fig. D). The mass was not pedicled, and was not associated with the wrist capsule, joint cavity, ulnar nerve vascular bundle, or median nerve. The mass was completely separated from the capsule and the peripheral muscle bundles and sarcolemma were removed (Fig. E). After fully stopping the bleeding, the incision was rinsed and closed layer by layer. The mass was dissected after operation, and the section was composed of homogenous, yellow fine adipose tissues, with no clear infiltration, fibrosis, thrombosis, or necrosis of the muscle bundles (Fig. F). Pathological examination indicated a lipoma with no pathological changes in the muscle bundle and sarcolemma.
The resection was completed on an outpatient basis, and the patient went home immediately after the procedure. No antibiotic or pain medications were required. The symptoms of swelling and pain were resolved within 3 weeks post-surgery, and there was no clear abnormality in wrist and finger movement and sensation. There was no recurrence in 2 years of follow-up.


A 67-year-old female was brought to the emergency room for three episodes of unprovoked syncopal attack. Electrocardiogram (ECG) monitoring showed long pauses with atrial activity but no ventricular activity and additionally revealed trifascicular block with intermittent complete heart block (CHB) (. She reported a history of right breast malignancy, hypothyroidism, diabetes, and hypertension. She had been subjected to modified radical mastectomy, radiotherapy, and intravenous chemotherapy previously in 2009. Chemotherapy was delivered through a venous access port implanted through the right internal jugular vein (. Subsequently, she had experienced a recurrence with metastasis to the bone and lungs. At the time of the current presentation, she was taking 50 mg of atenolol in tablet form (Aten; Zydus Cadila, Ahmedabad, India), 125 mg of palbociclib in tablet form (Palbace; Pfizer, New York, NY, USA), and 2.5 mg of letrozole in tablet form (Healing Pharma, Mumbai, India) daily. A 24-hour Holter recording was obtained after cessation of the atenolol for 72 hours, which revealed long pauses with atrial activity and no ventricular activity. Considering the patient’s symptoms and long cardiac pauses, a permanent pacemaker was implanted after discussing the role of the pacemaker with both the patient and her family.
Under local anesthesia, a temporary pacing lead was inserted via the right femoral vein and placed at the right ventricular apex. Additionally after local anesthesia, the left axillary vein was punctured using an 18-gauge Seldinger needle. When a 0.032-in guidewire inserted through the needle met with resistance (, it was withdrawn and contrast was injected through the needle (. Venography revealed distal total occlusion of the left subclavian vein and extensive venous collaterals. At this point, a 0.014-in percutaneous transluminal coronary angioplasty (PTCA) guidewire was negotiated across the subclavian vein and innominate vein into the inferior vena cava under fluoroscopy (. A 6-French sheath was then threaded over the PTCA wire into the axillary vein and the distal subclavian and left innominate vein were dilated serially with a 2-mm × 10-mm coronary PTCA balloon followed by a 4-mm × 20-mm peripheral balloon (. Subsequently, an active fixation (screw-in) pacing lead was implanted into the right ventricular apex (.


A 46-year-old woman presented with a 7-year history of intractable hiccups that had worsened over the past 3 years. Seven years ago, the patient had experienced an episode of depression accompanied by occasional hiccups after social disputes. In such cases, the hiccups resolved spontaneously without treatment. Fifteen days after the depressive episode, the hiccups began to occur frequently, especially at night; each episode lasted 3 to 4 hours, preventing the patient from sleeping. The patient's hiccups were induced by angry emotions and cold or rainy weather. After 30 days, these hiccup attacks became more frequent; still, each episode lasted 3 to 4 hours. Each attack was accompanied by chest and abdominal convulsions and pain as well as asphyxia. The patient felt frightened. Her hiccups were sometimes relieved by pinching the skin between her eyebrows. The patient subsequently noted that her episodes of hiccups could also be temporarily relieved by pinching the lumbosacral skin.
The patient was admitted to the local hospital. Gastroenteroscopy showed no abnormalities; spasmolysis and sedation drugs were prescribed, but they provided no benefit. Then, the patient was treated with traditional Chinese medicine (>1000 doses), but this exacerbated her hiccups. Physical examination revealed a pale complexion, dull expression, and continuous attacks of hiccups. During each attack, the patient was forced to bend down. She complained of chest tightness, dyspnea, palpitations, dreaminess, dysphoria, intolerance of cold, and hypohidrosis. She preferred hot drinks. The patient's blood pressure, heart rate, respiration, pulse, and other vital signs were all normal. After the patient had provided written informed consent, she underwent extracranial acupuncture treatment for the first time.
A sitting position was adopted, with the patient's hands folded on the treatment bed. The patient's head was bent forward, with hers forehead against the back of her hands. The acupuncture point was located 0.5 cm distal to the point of attachment between the occipital ligament and the external occipital protuberance. After routine skin disinfection, the distance between the skin and the bone surface was evaluated with one hand holding the needle and the other hand pressing the skin at the acupuncture point. Then, the tip of the needle was placed against the skin and quickly inserted. After the percutaneous puncture, the needle angle was adjusted to ensure that the needle was perpendicular to, and in contact with, the bone surface. Then the acupuncturist's auxiliary hand quickly squeezed the lower part of the needle, until it had penetrated approximately 1 mm into the bone. Once the needle had been clamped by the bone, the needle was pulled out (Fig. ). Sterile gauze was applied to the acupuncture point with pressure for about 5 minutes. Ten minutes after the treatment, the patient's symptoms (including chest tightness, dyspnea, and hiccups) had completely disappeared. The patient was relaxed and in a comfortable mood. The first acupuncture treatment gave the patient more confidence. The patient's subsequent treatment included 10 acupuncture sessions (once daily), with the acupuncture point repositioned 1.5 to 2 cm distally toward the top of the head each time. After the first therapeutic course, the duration of the patient's nighttime hiccups decreased to 1 hour, and the quality of her sleep improved. The duration of the patient's daytime episodes of hiccups decreased to 2 hours. The patient then underwent a second course of treatment after a 7-day interval. During this period, acupuncture was performed every 2 days. After the second course of treatment, the patient experienced an episode of hiccups every other day but reported no continuous attacks. The hiccups had resolved completely by the time the patient had completed 3 courses of treatment. During a follow-up period of 1 year, the hiccups did not return.


A 75-year-old man was admitted to the Department of Gastroenterology with a 7-day history of persistent hiccups and hematemesis for 3 hours. A diagnosis of Mallory-Weiss syndrome was made. Seven days prior to admission, the patient caught a cold and experienced an episode of hiccups (20 per minute) that lasted for 1 hour. The patient's hiccups were transiently relieved by drinking water but aggravated by eating. No specific treatment was given. Three hours before admission, the patient's hiccups began to be accompanied by nausea and hematemesis (about 15 mL per episode). There was no melena, dizziness, fatigue, ataxia, syncope, palpitation, chest or abdominal pain, or abdominal distension. The patient had a 15-year history of hypertension and a 7-year history of diabetes, and he regularly took oral nifedipine and subcutaneous insulin. Fourteen years earlier, the patient had undergone coronary artery bypass surgery; since then, the patient had taken oral isosorbide mononitrate. Three years prior to presentation at our hospital, the patient had undergone surgical resection of nucleus pulposus caused by lumbar disc herniation; he recovered rapidly from the procedure. One year prior to presentation at our clinic, the patient had been implanted with a stent because of cerebrovascular stenosis; since that point, he had been prescribed oral clopidogrel. On admission, the patient's body temperature was 36.9 °C; heart rate was 96 bpm; respiratory rate was 22 breaths per min; blood pressure was 110/80 mmHg. The results of the patient's laboratory tests were as follows: white blood cells 6.26 × 109/L, hemoglobin 115 g/L, fibrin 3.22 mg/L, prothrombin 12.3 second, and international standardized ratio 1.15.
After admission, a diagnosis of acute erosive-hemorrhagic gastritis was suspected. Oral omeprazole, hemocoagulase, octreotide acetate, and vitamins were administered. The patient's persistent hiccups were treated using traditional Chinese acupuncture, but there were no remarkable benefits. Then, extracranial acupuncture was performed according to the methods described in case 1. The acupuncture point was located 0.5 cm distal to the point of attachment between the occipital ligament and the external occipital protuberance. Immediately after the first extracranial acupuncture, the patient's hiccups disappeared; they did not recur thereafter. During a 6-month follow-up period, the patient remained asymptomatic.