Case 1 was a 55-year-old male heavy smoker with a history of epigastric pain and melena for about one month. Physical examination showed conjunctival pallor but no palpable mass. Laboratory analysis demonstrated anemia (Hct 24.9%) and leukocytosis (WBC 10.6 × 109/L), while other laboratory results were almost normal, including electrolytes, blood sugar, tumor markers, liver and renal function. A previous CT scan from another hospital had demonstrated a mass in the left upper lobe.
A gastroscopy was performed to investigate the cause of melena and anemia, which detected erosive gastritis, dodecadactylitis and mild esophagitis. PET/CT images revealed a peripheral mass with intensely increased 18F-FDG uptake in the left upper lobe measuring 3.7 × 3.3 × 3.1 cm. The maximum standardized uptake value (SUVmax) was calculated to be 33.2, which indicated a considerable high possibility of malignancy. The CT images of the lung mass showed both carcinomatous features including lobulation, irregular cavity, spiculation and pleural retraction, and sarcomatoid features including increased size, obvious necrosis unmatched with size, pleural involvement, and cavitation within the tumor. The mediastinal lymph node next to the aortic arch was mildly enlarged, measuring 1.5 × 0.9 cm with a SUVmax of 3.4. It is unusual for an enlarged lymph node to be palpated in the area beside the aortic arch and several mediastinal lymph nodes with this metabolic pattern have been proven by surgery to be metastasic in clinical practice, and this lymph node was therefore considered as suspect mediastinal lymph node metastasis.
A left adrenal gland mass with obvious necrosis and remarkably increased FDG uptake was detected (SUVmax: 30.8; size: 7.6 × 5.1 × 5.0 cm), which was suspected to be metastases. Circumferential thickening of the small intestinal wall (up to 2.5 cm thickness) was found incidentally in the right middle abdomen (Fig ), with intense FDG uptake (SUVmax: 41.6). The length of the involved intestine was about 4.5 cm. Based on these findings, we concluded that the patient had a possible intestinal metastasis of pulmonary sarcomatoid carcinoma. Subsequent pathology results from a CT-guided biopsy confirmed adenocarcinoma, and immunohistochemical (IHC) staining results were as follows: cytokeratin (CK) (+); CK5/6 (−); P40 (−); thyroid transcription factor (TTF-1) (+); programmed cell death 1 (PD-1) (5%+); programmed cell death 1 ligand 1 (PD-L1) (80%+); Ki-67 (70%+); CK20 (−); CK7 (+); villin (−); and Satb2 (−). The surgical specimen of the intestinal mass following laparoscopic surgery showed poorly differentiated carcinoma with local sarcomatoid differentiation, infiltrating the whole layer with visible nerve and intravascular tumor thrombus, with IHC markers CK (+); CK7 (+); CK20 (−); TTF-1 (+); vimentin (+); CD34 (vessel+); CD31 (vessel+); ETS related gene (ERG) (vessel+); CD117 (−); Dog-1 (+); P63 (−); desmin (−); smooth muscle actin (SMA) (−); S-100 (−); and Ki-67 (70%+) (Fig ). Taking the IHC markers into consideration, this patient was diagnosed as PSC with intestinal metastasis. He died four months after surgery.


Case 2 was a 61-year-old man whose main complaint was of melena of more than one month’s duration, and an intermittent fever up to 39.7°C for more than 20 days. He denied any symptoms of cough or abdominal pain, or other pulmonary or gastrointestinal discomfort. Gastrointestinal endoscopy at a local hospital had demonstrated an antral ulcer with normal intestinal mucosa. There was no improvement after administration of Yunnan white medicinal powder and colloidal bismuth pectin capsules. Initial laboratory tests indicated iron deficiency anemia and an albuminemic state with low hemoglobin (Hb) (73 g/L), total protein (51.1 g/L), albumin (27.5 g/L), prealbumin (39 mg/L), serum iron (2.3 umol/L) and total iron binding capacity (35.44 umol/L) level. The other laboratory results were normal, including electrolytes, blood sugar, tumor markers, hepatic and renal function.
18F-FDG PET/CT showed an irregular large mass about 4.7 × 3.3 × 3.5 cm, with an SUVmax of 13.4 in the left upper lobe. The lesion showed malignant features including an irregular margin, lobulation, spiculation, pleural traction, and obvious necrosis of more than 30% without bronchial stricture and occlusion (Fig ). The bilateral hilar lymph nodes were mildly enlarged with high density and symmetrically increased 18F-FDG uptake (SUVmax: 4.0–5.3), and were considered as lymphadenitis. Meanwhile, 18F-FDG PET/CT detected wall-thickening of the descendant duodenum and part of the jejunum in the left upper quadrant of the peritoneal cavity with SUVmax of 10.4. The local intestinal cavity was dilated, and the surrounding fat gap was clear.
Histopathological results from CT-guided puncture of the pneumonic lesion suggested poorly differentiated NSCLC with massive necrosis, indicating PSC with IHC markers AE1/AE3 (+), vimentin (+), P40 (−), TTF-1 (−), S-100 (−), SMA (−), desmin (−), and Ki-67 (20%+). Subsequent gastroscopy demonstrated nodular eminence at the descendant duodenum with an obscure boundary, erosion and necrosis of the mucosal surface with dirty moss-like appearance (Fig ). Biopsy of the duodenum confirmed a poorly differentiated carcinoma with AE1/AE3 (+), CK7 (+), CK19 (−), CK8/18 (+), hepatocytes (−), epithelial membrane antigen (EMA) (+), TTF-1 (−), and Ki-67 (approximately 60%+) (Fig ), indicative of sarcomatoid carcinoma. The patient survived for five months after diagnosis.


A 28-year-old man, with a history of CoA repair using Dacron patch aortoplasty at the age of 10 years, presented with shortness of breath and sudden, severe central chest pain that radiated across his chest and back. The patient had been lost to clinical follow-up over the last 15 years. He was conscious, hypotensive (90/60 mmHg on both arms), and in distress with tachycardia (120 BPM) and relatively weak pedal pulses with cold distal extremities. A chest X-ray (CXR) demonstrated the widening of the upper mediastinum (Figure ).
He underwent emergency CT angiography, which demonstrated extensive mediastinal hematoma and contrast leaking from a 4x12 cm complex pseudoaneurysm of the proximal thoracic descending aorta (Figure ).
The intimal disruption started about 2 cm distal to the origin of the left subclavian artery (LSCA), which was probably the site of the patch repair. The aortic diameter just prior to the disruption was 2.5 cm, and the normal distal thoracic aortic diameter was 2 cm. Of note, there was compression to the distal aorta by the pseudoaneurysm, leading to significant narrowing, which explained the weak distal pulses and cold extremities. After the heart-team discussion, the decision was made to proceed with transcatheter endograft implantation. The transcatheter approach was deemed more feasible and safer than a surgical one, especially in the presence of a good landing zone for endograft placement (away from the LSCA) (Figure ).
The patient was taken to cardiac catheterization laboratory and, under general anesthesia, we implanted a tapered (28 mm - 26 mm) x 150 mm Valiant Thoracic Stent Graft with the Captivia Delivery System (Medtronic Vascular, Santa Rosa, CA). The endograft was implanted successfully with complete exclusion of the pseudoaneurysm and excellent flow distally (Figure ).
The access site (right femoral artery) was secured successfully with two Perclose ProGlide™ devices (Abbott Laboratories, Abbott Park, IL). The patient did very well and was discharged home after three days. A follow-up CT angiography revealed a widely patent stent graft with no endoleaks.


A 29-year-old male with a history of IV drug use, without any known comorbidities presented to the hospital with complaints of neck and back pain for three weeks. He denied any fever or chills, any radiation of pain, or any numbness or tingling. He was seen earlier in the emergency room during that week, given a shot of IV ketorolac for pain, and then discharged. The patient's physical exam was unremarkable for any focal neurological deficits. His illness did not subside, the pain worsened, and he subsequently presented later in the week with worsening neck and back pain. He also complained of an abscess on his right leg, located above the lateral malleolus with clean edges that he first noticed two to three weeks ago. At the time of presentation, he was alert and oriented, and vitals were within normal limits. The computed tomography (CT) scan revealed osteomyelitis at the cervical vertebra (C4-C5) level and prevertebral fluid collection. Neurosurgery was consulted, and magnetic resonance imaging (MRI) was recommended, which revealed C4-C5 osteomyelitis with an epidural abscess. The patient was started on IV vancomycin and admitted to the floor. During his hospital stay, neurosurgery performed an anterior corpectomy and posterior cervical instrumented fusion. The procedure was complicated by a cerebrospinal fluid (CSF) leak, and intraoperative cultures grew Serratia marcescens, as shown in Figure . The patient’s hospital course was complicated by the CSF leak and drainage from the surgical wound, for which he had to be taken back to the operating room (OR) for an anterior washout. A lumbar drain was placed that day for drainage. Infectious disease recommended adding aztreonam 2 g IV every eight hours for six weeks. Vancomycin was discontinued after the cultures did not grow methicillin-resistant Staphylococcus aureus (MRSA). Blood cultures were also negative during his hospital stay. The patient completed six weeks of treatment with IV aztreonam and was discharged home after completion of the antibiotics course. He was followed up in the clinic where his condition has significantly improved and he did not have any active complaints during that visit.


A 69-year-old woman presented with a 19-month history of pain and an enlarging soft tissue mass in the ulnar aspect of the PIP joint of the fifth finger of the left hand. She was a housewife who performed no particular work or sporting activity. She had a history of minor trauma involving bruising of the finger in a door and was referred to a neighboring clinic 14 months before the visit to our hospital. Plain radiographs taken at the previous clinic had shown no sign of fracture, but instead revealed an abnormal calcifying lesion of the soft tissue of the left fifth finger. She had visited several clinics and hospitals and had been treated with analgesics and splinting for more than 2 months, but the pain in the finger had gradually worsened. Thus, she was referred to our hospital for definitive diagnosis and treatment.
Physical examination revealed tenderness around the PIP joint of the fifth finger with an apparent subcutaneous tumor, measuring around 1 cm in diameter (Figs. A and B). She experienced pain around the PIP joint of the fifth finger when the fist was tightly clenched and/or when the lesion contacted another object. There were no signs of infection or neurovascular disturbances, and no history of previous infection. The range of motion of the affected PIP joint was slightly more restricted than that of the contralateral side, but there was no functional impairment of the finger. Blood chemistry analysis showed no signs of inflammation or other abnormalities.
Plain radiographs of the fifth finger taken 5 months before the initial visit to our hospital revealed a well-defined calcified soft tissue mass overlying the ulnar side of the proximal and middle phalanges that was well separated from the adjacent bone, with no periosteal reaction (Figs. A and B). Radiographs taken at the time of presentation at our hospital revealed an enlarged 2-humped calcifying lesion overlying the ulnar side of the PIP joint (Figs. C and D). Computed tomography also showed a well-defined and rimmed calcifying soft tissue mass with calcification of the outer margins on the ulnar side of the left fifth finger, without bony destruction (Figs. A–D). T1- and T2-weighted magnetic resonance imaging (MRI) showed a well-defined soft tissue mass with low signal intensity overlying the ulnar side of the proximal and middle phalanges (Figs. A–D). T1-weighted MRI also showed that the lesion was well separated from the adjacent bone and surrounded by a diffuse high-intensity area, suggesting perilesional soft tissue edema. No periosteal reaction was detected. Moreover, there was no abnormal intensity in the bone marrow observed on either T1- or T2-weighted MRI, suggesting no progression to the bone marrow. Contrast-enhanced MRI showed no enhancement of the soft tissue mass (Fig. E). There was no cartilaginous matrix formation. Taken together, these imaging modalities indicated a well-defined subcutaneous calcifying mass with a characteristic peripheral radiopaque ring overlying the ulnar side of the proximal and middle phalanges, suggesting a benign calcifying lesion, namely a calcifying deposit. An excisional biopsy was recommended to achieve a definitive diagnosis, but this was declined by the patient. Thus, no invasive treatments were administered, and she was treated with analgesics and encouraged to massage the affected finger.
The pain in the left fifth finger gradually improved during the following 6 months. In addition, the limited range of motion completely recovered, and follow-up radiographs showed complete resolution of the calcifying mass at 6 months after the initial visit to our hospital (Figs. A and B). At the final follow-up conducted 3 years after the initial visit to our hospital, the patient had a full range of motion without recurrence of acute calcific arthritis.


A 53-year-old man sought help to emergency department because of the increasing swollen left shank for 1 day, with intermittent pain, pulselessness and pallor. He denied any history of drug abuse, trauma, local infection, intermittent claudication, previous surgery, rheumatic heart disease, atrial fibrillation or infective endocarditis. Blood pressure of our patient was 162/95 mmHg, with no cardiac murmurs and peripheral bruits. Physical examination revealed swelling of the left leg and a palpable pulsatile mass. Pulsation of the dorsalis pedis artery (DPA) and PTA were vanished. Skin temperature of the shank was measured by an infrared thermometer (Bailing Medical Equipment Co. Ltd. China). The cyanotic left toes were clearly visible (Fig. A). Blood tests, echocardiography and electrocardiogram (ECG) of our patient were normal. Ankle-brachial index (ABI) of our patient measured by Vista AVS (Summit Doppler Systems, Inc. USA) was abnormal. Ultrasound images showed a PSA with a volume of 79 mm × 62 mm and a neck diameter of 3.69 mm (Fig. B and C). Computed tomographic angiography (CTA) images revealed a 61.7 mm × 72 mm PSA of the left shank (Fig. A and B). Soft tissue dropsy of the left shank was clearly visible in the image (Fig. C). Three-dimensional reconstruction image showed the volume of PSA and disruption of PTA (Fig. D). PSA was so large that it compressed muscles of the calf and some of main arteries of the calf. Therefore, we selected open surgery to remedy our patient.
Blunt dissection of calf muscle groups was operated during the operation. PSA was punctured to relieve the pressure of the left calf (Fig. A). A mass of intraluminal thrombus and clots were removed (Fig. B and C). A perforation was found in PTA which was repaired with 6–0 blood vessel sutures after the tibial nerve was protected (Fig. D). Pulsation of PTA was recovered well after the operation. Histological examination confirmed intraluminal thrombus of PSA with inflammatory cells, without any evidence of disorders of connective tissue, necrotizing vasculitis and arteritis (Fig. A and B). Skin temperature and ABI of the left shank after surgery were significantly improved compared with those before surgery. Antibiotic therapy (Ceftezole Sodium) was appropriately given for 7 days after surgery. He was discharged 9 days after surgery with no complication.
Regular activity of our patient came back a few weeks after discharge. Walking distance of the patient was undiminished. At 6-month follow-up visit, we found the left lower extremity showed a well-healing surgical incision (Fig. C). Pulsations of left PTA and DPA were easily palpable. Skin temperatures of the left shank and foot were equal to the opposite side (Table ). ABI of the left lower extremity also improved significantly compared with the previous test (Table ). Ultrasound images showed that the blood supply of popliteal artery and its branches in the left lower extremity recovered well (Fig. ). Our patient had no recurrence of PSA and no clinical symptom at 2-year follow-up.


A 49-year-old woman presented to our hospital with arthralgia, nausea, and fever lasting for seven days and chest pain over a few days. Laboratory data showed elevated serum troponin I level. Echocardiography showed reduced left ventricular (LV) ejection fraction (LVEF) with anterior wall motion abnormalities. The patient was admitted to our hospital because myocardial infarction or myocarditis was suspected.
She had no significant medical history or known drug allergies. On admission, chest pain, nausea, and inappetence persisted. Although blood pressure values were normal, she had physical fatigue and sinus tachycardia with minimal exertion. Laboratory data on admission showed a white blood cell count of 4460/μL, including 7.2% eosinophils (eosinophil count: 321/μL), serum creatine kinase (CK) level of 147 U/L (CK-MB: 3.7 ng/mL), troponin I level of 0.47 ng/mL, and B-type natriuretic peptide (BNP) level of 109 pg/mL. The levels of immunoglobulin and autoantibody were within normal limits.
The electrocardiogram showed sinus rhythm with low voltage in limb leads and poor R progression in precordial leads (). Thoracic radiography excluded cardiomegaly, pleural effusion, or pulmonary congestion (). Echocardiography revealed a LV end-diastolic diameter of 50 mm and LVEF of 42% with hypokinesis in the LV anterior region.
Coronary angiography showed no significant stenosis. Three endomyocardial biopsy specimens were obtained from the right interventricular septum. Myocardial specimens showed abundant lymphocytic infiltration with interstitial edema and slight perivascular fibrosis (). Very few eosinophils and no giant cells were found in the specimens. Based on these findings, she was pathologically diagnosed with acute lymphocytic myocarditis. However, a close observation of the specimens revealed eosinophils with degranulation (). Eosinophil degranulation was also confirmed by direct fast scarlet stain (DFS) and immunostaining for major basic protein (MBP) (Figures and ).
On the next day after admission, peripheral blood eosinophil count decreased from 321/μL to 162/μL, whereas serum troponin I level continued to rise from 0.47 ng/μL to 1.007 ng/μL. Her symptoms (chest pain, nausea, and inappetence) persisted, and LVEF remained 45%. Although she was diagnosed with lymphocytic myocarditis, we decided to initiate steroid therapy because of the presence of eosinophil degranulation in the biopsy specimens. Methylprednisolone was administered at a dose of 1,000 mg/day for 3 days. Echocardiography performed 12 hours after the first administration of methylprednisolone showed marked improvement of LVEF from 45% to 65% () and normalization of regional wall motion. The pulse rate decreased and symptoms improved. On the following day, serum troponin I level decreased from 1.007 ng/μL to 0.152 ng/μL (). Because of a dramatic response to high-dose steroid therapy, methylprednisolone was changed to oral prednisolone at a dose of 30 mg/day and tapered carefully. The troponin I level normalized by the eighth day after the first administration. The patient was discharged 20 days after admission with a normal LVEF and BNP level of 6.4 pg/mL. Paired serum viral antibodies for adenovirus, influenza virus, coxsackievirus, and enterovirus were all negative. The dose of oral prednisolone was tapered over 6 months to 2.5 mg/day and finally discontinued. There was no further recurrence of LV dysfunction or elevation of serum troponin I level.


A 26-years-old man presented to the senior author for evaluation of bilateral heel pain, more severe on the right foot, for five months. He played hockey and tennis as leisure sports and worked as a dairy-cheese maker.
The physical examination demonstrated normal alignment of the lower extremities, straight hindfoot with painless limited motion of the subtalar joint bilaterally. Elective pain was present on both sides at the insertion of the Achilles tendon. The first tarsometatarsal (TMT1) joint was hypermobile and painless bilaterally.
Standard X-rays showed insertional Achilles calcific spurs, an incidental finding of osseous cubonavicular coalition on the right foot (Figures and ), and irregularity of the cubonavicular and calcaneonavicular articular surfaces on the left foot (). Arthritic changes were visible on the dorsal aspect of the first tarsometatarsal joint on both feet (). Medial foot arch was normal with a Djian-Annonier angle of 123° on both sides (angle defined between a line tangent to the inferior surface of the calcaneus and a line between the inferior point of talonavicular joint and the inferior point of the medial sesamoid, with normal value defined between 120 and 128° []).
MRI of the right foot showed insertional Achilles tendinosis and an osseous coalition between the navicular and the cuboid (), as well as arthritic changes of the TMT1 (). Computed tomography of both feet was also performed and confirmed the osseous cubonavicular coalition on the right foot (), associated with a partial osseous coalition between the cuboid and the third cuneiform and bone irregularities between the first and second cuneiforms suggesting a nonosseous coalition (), as well as arthritis in the tarsometatarsal joint (). On the left foot, a nonosseous calcaneonavicular associated with a cubonavicular coalitions was diagnosed ().
As the patient was not symptomatic of this midtarsal arthritis and of his rigid hindfoot, no surgical treatment was proposed. Insertional Achilles tendinosis was treated with physical therapy and foot orthoses with success.


A 42-year-old male patient presented with irregular bowel movements and abdominal pain, requiring multiple hospital admissions. During these admissions, a splenic mass was identified radiographically. While this was deemed not to be the source of the irregular bowel movements, an ultrasound of his abdomen during one of these admissions 3 years prior to our evaluation revealed a left upper quadrant mass. This was subsequently assessed with computed tomography (CT) scan, which identified a fatty mass potentially arising from the spleen or adrenal gland. The mass was initially found to be 5.6 cm in size but was noted to be growing in size on repeat imaging 2 years later, with a subsequent measurement of 6 cm in size. He was advised to see a surgeon, but due to an upcoming move, he delayed further evaluation and work-up. Once settled, he established himself with a primary care physician and underwent CT scan 1 year later showing a 7.6 × 7.1 × 6.4 cm splenic mass (), which was larger than before. The mass was largely fat containing with a differential diagnosis including lipoma, myelolipoma, or dermoid cyst. Potential neoplastic etiologies included liposarcoma, which was of primary concern secondary to the growth of the lesion over time. There were no obvious features of de-differentiation or metastasis, and the mass was entirely within the spleen with no involvement of the adrenal gland. On our assessment, the patient was generally well appearing, overweight (BMI 31), with an abdominal exam that was benign with a nonpalpable spleen, and only minimal tenderness to palpation in the left upper quadrant. His heart rate was nontachycardic at 84 beats per minute. His blood pressure was normal at 139/79, and he was afebrile. His laboratory studies included complete blood count (CBC) and complete metabolic panel (CMP). CBC revealed an elevated hemoglobin at 16.8, white blood cell count of 6.6, and platelet count of 200. CMP revealed mild transaminitis with AST and ALT of 42 and 81, respectively, with other values within normal limits.
Percutaneous biopsy was not obtained due to concern for hemorrhage, and that as the mass was growing, surgery was recommended regardless of the biopsy findings. He was counselled on the risks and benefits of open splenectomy, as well as alternatives including observation. As the mass was growing in size and due to concern for sarcoma, the patient wished for operative intervention. An open approach was favored due to the overall size of the spleen along with concern for sarcoma. He gave consent to proceed with the operation. Presplenectomy vaccines were administered 2 weeks preoperatively.
Splenectomy was performed through a left subcostal incision. There was significant adhesive disease (presumably inflammatory in nature as he had not had prior abdominal surgeries) in the left upper quadrant, but the spleen was amenable to be removed intact and without violation of the mass. The patient had an unremarkable postoperative course and recovered well. Pathology identified the mass to be 8.5 × 8 × 6 cm, well-circumscribed, and with a yellow/tan heterogeneous cut surface (). Microscopically, the mass was found to be composed of mature fibroadipose tissue with islands of hematopoietic cells including scattered nucleated red blood cells and rare megakaryocytes. This was consistent with the diagnosis of a splenic myelolipoma. At 7 months of follow-up, the patient continued to do well.


A 17-year-old pregnant female, a recent Guatemalan immigrant with no known past medical history, presented to an outside adult hospital with abdominal pain at 16 weeks' gestation. She was found to have had a spontaneous abortion and underwent a dilation and curettage. Histology of amniotic sac contents showed a phenotypically male fetus with no identifiable gross abnormalities, immature internal organs with mild autolytic changes, acute chorioamnionitis, and a trivascular umbilical cord. Placental histology showed fragments of immature placental tissue and necrotic decidua.
Two weeks later, she presented to a pediatric hospital for three days of worsening abdominal pain, diarrhea, nausea, fever, and cough. Physical exam was remarkable for thin appearance, tachypnea, and suprapubic abdominal tenderness without rebound or guarding. Initial labs revealed leukocytosis with neutrophil predominance, acute kidney injury, and synthetic liver dysfunction. CT angiogram of the chest obtained for hypoxemia demonstrated an apical lung cavity with extensive interstitial thickening and micro-nodularity throughout both lungs (Figure ), while CT abdomen and pelvis showed small bowel thickening, significant nodular omental thickening, and ascites (Figure ). A pelvic ultrasound revealed a complex, septated fluid collection in the pelvis, endometrial thickening, and right upper quadrant ascites (Figure ). Notably, no lymphadenopathy was seen on CT scan. Due to concern for septic shock secondary to endometritis, the patient was started on broad-spectrum antibiotics and subsequently transferred to an adult tertiary center where she required intubation for acute hypoxic respiratory failure.
Although TB was on the differential at transfer, lack of lymphadenopathy on imaging was considered unusual for this presentation; however, a repeat dilation and evacuation revealed necrotizing granulomatous endometritis with moderate numbers of Mycobacterium tuberculosis (M. tuberculosis) bacteria, and degenerative first trimester products of conception (Figure ). Bedside paracentesis also demonstrated M. tuberculosis in ascites fluid (Figure ). Endometrial swab performed days following dilation and evacuation revealed numerous M. tuberculosis organisms(Figure ). Bronchoscopy/bronchoalveolar lavage (BAL) was performed, which revealed pulmonary M. tuberculosis. Human immunodeficiency virus (HIV) screen and a serum QuantiFERON®-TB Gold testing were both negative. Rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy was initiated, and the patient completed a three-week course of piperacillin-tazobactam given the initial septic presentation with retained products of conception.
Although the patient hemodynamically stabilized and was successfully extubated, despite two weeks of RIPE, she continued to spike fevers and experience night sweats. A complete MRI spine was performed to screen for spinal involvement and showed L2-L3 disc desiccation and a Schmorl’s nodule, but no active infection (Figure ). An MRI brain revealed two restricted diffusion lesions concerning for septic emboli, and subtle linear enhancement along the 7th, 8th, and cisternal trigeminal nerves, suspicious for early basilar meningitis (Figure ). A lumbar puncture was performed with cerebrospinal fluid studies, which came back negative for active TB. Repeat fallopian tube fluid sampling after nearly five weeks of RIPE therapy continued to demonstrate numerous acid-fast bacilli.


A 37-year-old woman, with a history of cholecystectomy due to recurrent biliary colic, came to the emergency room with complaints of abdominal pain and nausea for the last two days. The pain was in the epigastric region, 10/10 in intensity and cramping with radiation to the back. At the time of admission, the patient was hemodynamically stable with positive findings of epigastric tenderness on deep palpation. Blood pressure was 118/85 mmHg, heart rate of 88 beats per min and temperature of 97.6°F. Total bilirubin was 4.1 mg/dL with a direct fraction of 3.1 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 850 IU/L and 1025 IU/L, respectively. Serum amylase and lipase were elevated at 581 IU/L and 1328 IU/L, respectively. The patient was admitted under the impression of acute pancreatitis with Bedside Index of Severity in Acute Pancreatitis (BISAP) score of zero, Ranson’s Score on admission was one. CT scan of abdomen/pelvis without contrast showed CBD measuring 1.6 cm with intrahepatic biliary system dilation and mild peripancreatic fat stranding. On the second day, she developed a temperature of 99.6°F. Hepatitis immunity panel was negative for acute hepatitis. Patient was started on antibiotics (IV ciprofloxacin and metronidazole) for suspicion of acute cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) was done which showed mild dilated intrahepatic ducts; possible variant of Caroli disease, CBD dilation of 1.6 cm, and a choledochal cyst at CBD. Sphincterotomy was done and good bile drainage was reported. Post-procedure magnetic resonance cholangiopancreatography (MRCP) showed mild intra- and extra-hepatic biliary dilation. No focal filling defect was seen in the biliary tree. Post-ERCP, the patient improved clinically and subjectively. Laboratory values showed a downward trend and the patient was discharged on oral antibiotics.


A 40-year-old male who was a previous smoker with no other notable past medical history, presented with one week of fevers, chills, and non-productive cough and a right pneumothorax on chest radiograph. On presentation, he was saturating 79% on room air which improved to 86% on the non-rebreather mask at a flow rate of 12 liters per minute. A pigtail catheter was placed and subsequent chest radiographs showed the lung to be adequately re-expanded and a 10 cm curvilinear space in addition to bilateral lung infiltrates and air bronchograms (Figure ). The patient was admitted and tested positive for COVID-19 with reverse transcription-polymerase chain reaction (RT-PCR) evaluation of a nasopharyngeal swab specimen. A chest CT scan demonstrated a large complex pneumatocele in the right middle lobe corresponding to the curvilinear space seen on previous chest radiographs (Figure ). Extensive bilateral airspace disease was also noted on radiologic studies consistent with COVID-19 pneumonia. The patient had a complicated clinical course with the development of multiorgan failure and eventual death on admission day 60.


A 68-year-old male non-smoker with no notable past medical history presented with two weeks of cough, chest tightness, and vomiting. Initial oxygen saturation was 90% on room air and improved to 95% with facemask at a flow rate of 8 L/min. A chest radiograph showed bilateral infiltrates and he was admitted to the hospital where he tested positive for COVID-19. His oxygen requirements were weaned down and he was transferred to a lower acuity facility. However, nine days after discharge the patient returned to the emergency room with worsening respiratory distress. His O2 saturation was 70% on room air and improved to 90% with a non-rebreather mask at a flow rate of 15 L/min. A chest radiograph showed a large right pneumothorax along with a smaller left pneumothorax, pneumomediastinum, and subcutaneous emphysema. Bilateral chest tubes were placed. A subsequent radiograph showed bilateral lung re-expansion but with a right-sided ovoid lucency measuring 11.3 x 5 cm suggestive of a pneumatocele (Figure ). Extensive bilateral airspace disease was also noted in these radiologic studies. The patient was admitted and transferred to one of the several critical care units in the hospital. A chest CT scan confirmed the presence of an ovoid 12 x 4.8 cm air containing structure in the parenchyma of the right lower lobe probably representing a pneumatocele (Figure ). The left chest tube was removed on day five of admission while the right chest tube was removed on day 17. His oxygen requirements were weaned down during admission and he was discharged on day 25 on 3 L/min of oxygen.


A 58-year-old female with a past medical history of hypertension and no known smoking history was brought in to the emergency room after being found at home with altered mental status. In the emergency room, she required 15 L/min of oxygen by non-rebreather mask to maintain an oxygen saturation of 90%. A CT scan of her head did not show intracranial abnormalities but did show retropharyngeal gas. Further imaging showed extensive bilateral pulmonary infiltrates along with pneumomediastinum (Figure ), subcutaneous emphysema, and a small right upper lobe pneumothorax (Figure ). Also noted were right pulmonary artery thrombosis and left renal vein thrombosis. This patient also subsequently tested positive for COVID-19. Her pneumothorax was managed without pleural cavity decompression and her oxygen requirement was weaned down to 2-3 liters per minute at which time she was discharged home on day 21 of admission. Her thromboses were managed with anti-coagulation followed by placement of an inferior vena cava (IVC) filter due to gastrointestinal (GI) bleeding.


A 20-year-old Afghan origin male immigrant was referred to the Otolaryngology - Head, and Neck Surgery Department from a hosting structure in Greece, where he had been transferred for the last month. He complained of dysphagia, cephalalgia, and neck pain during the past two months. He did gargling with warm water and salt and received mild painkillers on his own initiative. No history of cough, chest pain, fever, or loss of appetite was reported. Furthermore, the patient noted no signs of trismus or difficulty in breathing. He reported no known allergies and no smoking or alcohol drinking habits. Overall, medical and family history was unremarkable.
On arrival, vital signs were within normal range (body temperature 36.6°C, heart rate 90 beats/min, blood pressure 117/75 mmHg). Palpation of both sides of the neck revealed tenderness, though, softness and no lymph nodes were noted. Examination of the oral cavity did not reveal any pathological finds and no projection of the posterior pharyngeal wall was observed. Endoscopy (flexible nasendoscopy) of the larynx displayed normal morphology and normal functionality of vocal cords. The lungs were clear to auscultation and no neurological deficit was noted on initial clinical examination. Basic laboratory data were within normal values: hemoglobin (Hb), 14.5 g/L; hematocrit (Hct), 45.5%; white blood cell count (WBC), 5,100 cells/mm3; platelets (Plt), 284,000 cells/m3; and C-reactive protein (CRP), 0.29 mg/L. Furthermore, HIV Elisa Test was negative. Chest X-ray only revealed pulmonary portal dilatation of both lungs (Figure ).
Due to persistent dysphagia, CT of the neck and chest was performed. CT of the neck revealed an extensive multilayered retropharyngeal abscess, reaching the prevertebral space and deepening marginally into the anterior mediastinum (Figures -). Chest CT demonstrated lesions in the form of ground-glass opacities in the upper part of the right lower lung lobe (Figure ).
The patient was subjected to intraoral aspiration of the retropharyngeal abscess under local anesthesia. Sample was sent for analysis. Sixteen milliliters of pus were able to be aspirated. Immediate relief was noted as far as neck pain is concerned. Cephalalgia soon receded and the symptom of dysphagia was reported to be improved. The results of direct microscopic examination by polymerase chain reaction (PCR) gene probe demonstrated MTB.
The patient underwent antitubercular therapy. A standard nine-month course of treatment with ethambutol, rifampicin, and pyrazinamide was planned in accordance with subsequently obtained sensitivities. In summary, the patient responded to the treatment. One month later the symptoms had resolved completely. During follow-up, the patient experienced no complication and went on to make a full recovery at the end of the chemotherapy course.


A 68-year-old man presented with left hip pain six weeks after a revision of his left total hip arthroplasty (THA). His original hip replacement surgery was performed 21 years prior to presentation and had required numerous revisions for wear of the joint and one surgery related to infection with methicillin-sensitive Staphylococcus aureus (MSSA) 13 years prior. Other notable medical history included uncomplicated right THA and left total knee arthroplasty (TKA) 12 and nine years prior to presentation, respectively, remote history of polysubstance use with alcohol, cocaine, and heroin (treated with suboxone), hepatitis C with sustained virologic response after sofosbuvir/simeprevir, cirrhosis, chronic kidney disease (stage III), coronary artery disease, and hypertension.
The patient’s chief complaint was acute left hip pain, which started two days prior to presentation and progressed until he was unable to bear weight. The patient also noted redness, swelling, small amounts of rust colored drainage from the surgical site, and subjective fever. He denied any recent trauma or contact with dirt or animals to the area. He had been using an unspecified topical cream on the area. He noted occasional oral ulcers but no recent jaw pain, jaw masses, dental procedures, or other complaints. He denied any other joint pain. At the time of presentation, he was febrile to 100.6˚F but hemodynamically stable without tachycardia. Physical exam was significant for two areas of surgical site wound dehiscence of 10 mm without visible purulence but with surrounding erythema, warmth, and fluctuance as well as limited passive hip flexion secondary to pain. Notably, there was no pain on passive internal or external rotation of the joint. His admission labs were notable for a white blood cell count of 9.9 x 1,000/mm3, erythrocyte sedimentation rate (ESR) of 114 mm/hr, C-reactive protein (CRP) of >190 mg/L, and serum creatinine of 4.6 mg/dL, slightly elevated from his baseline of 3.2 mg/dL.
Preoperative joint aspiration revealed cloudy fluid with 10,553 nucleated cells (100% neutrophils), and no visible crystals. Gram stain of that fluid was negative. He was started empirically on vancomycin pending cultures. He then underwent incision and drainage with exchange of the head and liner of the joint two days after he first presented. Culture of preoperative joint aspiration fluid and culture of intraoperative tissue biopsies grew Actinomyces. The subspecies was not determined but was found to be susceptible to ampicillin-sulbactam with a minimum inhibitory concentration (MIC) of <0.25/0.12 µg/mL by broth microdilution. Notably there was also growth of oxacillin-susceptible Staphylococcus epidermidis from broth enrichment of synovial fluid from the preoperative joint aspiration but not from any other specimen. A tunneled catheter was placed, and the patient was started on intravenous (IV) ampicillin-sulbactam and discharged to a skilled nursing facility on postoperative day 8 with a plan to continue IV ampicillin-sulbactam for a four-week course followed by eight weeks of oral amoxicillin-clavulanate, and likely lifelong prophylaxis with amoxicillin-clavulanate.


A 58-year-old female with a past medical history of hypertension presented with a four-month history of right shoulder pain, complicated with paresthesia to the right hand and decreased shoulder ROM. Her symptoms had impacted her ability to perform daily activities, including her duties as a nurse. The symptoms started within 24 hours of receiving an inactivated influenza vaccine, subjectively placed two inches below her deltoid (Figure ). Despite numerous visits to the emergency room, her primary care physician, and an orthopedic surgeon, her attribution of the pain to the vaccine injection was not taken into consideration. Before seeing an osteopathic physician, she was ultimately diagnosed with a cervical spine strain and right shoulder tendonitis. In that time, she had been treated with corticosteroid injections in the acromial bursa, nonsteroidal anti-inflammatory drugs (NSAIDs) in varying strengths, ongoing physical therapy, and was advised to schedule surgical intervention due to minimal improvement. At that time, the patient sought out an osteopathic family practice for a reassessment.
Surgical, family, and social history were noncontributory. Osteopathic physical exam revealed no visible skin changes or swelling. There was limited pan-directional passive and active ROM in the right shoulder, with marked limitation on abduction and pain on palpation of the injected site. ROM at the right elbow joint was unaffected. Light and deep pressures were felt equally along the right arm and hand. Spurling compression test for cervical radiculopathy was negative.
In reviewing her radiological history, plain radiographs of the cervical spine were unremarkable. Subsequent MRI of the right shoulder, six weeks after the vaccine was administered, demonstrated mild rotator cuff tendinopathy with a partial thickness rotator cuff tear, moderate bicipital tenosynovitis, and glenohumeral joint effusion. No fracture or dislocations were appreciated (Figure ).
After her initial osteopathic assessment, the patient elected for an injection of 1.0 mL methylprednisolone and 4.0 mL of 2% lidocaine in the area of vaccination to reduce local inflammation at the site of trauma. In subsequent follow-ups, she was prescribed a 4 mg oral methylprednisolone dose pack. When symptoms did not improve, osteopathic manipulation treatment was performed weekly for four months, in which a modified Spencer’s technique sequence with muscle energy was performed (Figure ). During this time, the patient also continued physical therapy and started acupuncture treatments to the right shoulder. She reported mild alleviation of pain and increased movement in select ranges of motion, but she was still unable to perform daily activities or return to work.
After four months of standard OMM techniques, OMM under general anesthesia, in this case propofol, was offered due to minimal improvement. The same modified Spencer technique was performed, along with additional manipulations such as a scapula lift. Status post-anesthesia recovery from the procedure, the patient was assessed for pain and ROM. Compared to the minimal pan-directional movement on initial presentation, the right shoulder joint was able to abduct passively to 180° and actively to 90°, flex passively to 180° and actively to 170°, and internally rotate to 45° in both active and passive ROM (Figure ). For one month after the procedure, the patient continued weekly acupuncture treatments, nonanesthetic osteopathic manipulations, and physical therapy to the right shoulder, with continued improvement of her symptoms. One additional osteopathic manipulation under anesthesia was performed at the end of the one-month period after which the patient demonstrated near full ROM of the right shoulder with only mild pain after 130° of flexion/abduction. She continues to have occasional OMM and physical therapy sessions; however, her pain and other symptoms have largely resolved.
Patient consent for this case presentation and pictures were obtained.


A 24-year-old male presented with neck swelling without signs of respiratory distress after a traumatic blunt neck injury. There was swelling of the anterior neck without palpable crepitus. Airway ultrasound showed disruption of the air–mucosal interface suggesting endolaryngeal disruption (Fig. b). CT scan confirmed the diagnosis of endolaryngeal disruption without cartilaginous fracture. The patient was conservatively managed and discharged well on the third day.


A 28-year-old male martial art athlete was kicked by his opponent and sustained a blow to the anterior part of the neck. He complained of pain, dysphagia and hoarseness. There was an abrasion to the anterior part of his neck, which was tender to palpation with localized crepitus.
Bedside airway ultrasound revealed a displaced fracture of the thyroid cartilage, disruption of anterior cortex of thyroid cartilage with surrounding mixed echogenicity denoting endolaryngeal edema (Fig. a and Additional file : Video S1) and paralyzed right vocal cord (Fig. e), consistent with Schaefer group 3.
Direct visualization using a flexible fibreoptic scope revealed an edematous and medially deviated right arytenoid with paralyzed and erythematous right vocal cord. He was intubated and intravenous dexamethasone, proton pump inhibitor, nebulized adrenaline and prophylactic antibiotic were initiated early in the emergency department. The patient was sent for CT neck after stabilization, which showed a defect in the posterolateral wall of the trachea with a displaced fracture of right anterior lamina of thyroid cartilage and superior cornu of left thyroid cartilage, consistent with Schaefer group 3 (Fig. b), and that found on bedside ultrasound. The patient was stable throughout his entire hospitalization after open surgical repair and was allowed home on day nine with outpatient follow up.


A 35-year-old male lorry driver hit his neck against the steering wheel when he thrown forwards during a head-on collision. He presented with neck pain, severe swelling over the whole anterior region of the neck, stridor, hypoxia and a compromised airway. The patient was immediately intubated and ventilated.
Focused airway ultrasound showed disruption of the air–mucosal interface, a displaced thyroid cartilage fracture with formation of endolaryngeal hematoma and a cricoid cartilage fracture (Fig. b). He was treated as Schaefer group 3 and was started on intravenous dexamethasone, proton pump inhibitor, nebulized adrenaline, prophylactic antibiotic and open surgical repair was planned.
CT scan revealed a defect in the posterolateral wall of the trachea with a displaced fracture of the left anterior lamina of thyroid cartilage and hematoma surrounding the thyroid and cricoid cartilages. This confirmed the classification and injury details categorized under Schaefer group 3, which correlated with that of ultrasound assessment. Hospital stay was uneventful, and he went home after 2 weeks, to be reviewed in the outpatient department.


A 51-year-old healthy female without significant past medical history presented to the emergency department with severe nonradiating abdominal pain that began without an inciting event. The pain was mainly located in the epigastric region. The pain was described as sharp and was associated with nausea; multiple episodes of nonbloody, nonbilious emesis; chills; and a near syncopal episode. There were no specific alleviating or exacerbating factors, and she never had similar symptoms in the past. She denied any fever, dysuria, history of heartburn, peptic/duodenal ulcer disease, heavy nonsteroidal anti-inflammatory drugs (NSAID) use, recent illnesses, recent ill contacts, or recent travel. She denied any significant surgical history. She is a former heavy smoker and reported current moderate alcohol use and a recent increase in her stress level. The patient denied a prior history of EGD or colonoscopy. Family history is significant for coronary artery disease in both parents.
In the emergency department, she was found to be hypotensive with a blood pressure of 64/48 mmHg and a heart rate of 71 bpm. Her oxygen saturation was 100% on room air. Physical exam revealed a diffusely tender abdomen. Lab tests were significant for a hemoglobin of 9.1 g/dL and a white blood count of 14.4 k/μL. Subsequently, 2 large-bore intravenous (IV) catheters were inserted and a blood type and screen were ordered. IV fluids were started along with pain and nausea control medications.
A contrast-enhanced CT scan of the abdomen and pelvis revealed a large retroperitoneal hematoma with a lobulated focus of active contrast extravasation interposed between the pancreatic head and the duodenum (). The bleeding was localized to the retroperitoneum itself and did not involve nearby retroperitoneal organs such as the pancreas, kidneys, or duodenum; however, these organs did show displacement by the hematoma. Several nearby vessels were identified as the potential source of bleeding including the distal gastroduodenal artery as well as several prominent superior and inferior pancreaticoduodenal (PDA) arteries extending from the gastroduodenal and superior mesenteric arteries, respectively. Finally, a high-grade proximal celiac artery stenosis was noted consistent with median arcuate ligament compression (). Interventional radiology (IR) and general surgery were consulted, and a mesenteric angiogram was emergently performed to localize the bleeding for potential embolization.
Mesenteric angiography confirmed median arcuate ligament compression that was well compensated through brisk extensive collateral flow from the SMA via the pancreaticoduodenal arcade (). Embolization of an inferior pancreaticoduodenal (PDA) branch was performed with detachable 0.018-inch coils given active extravasation. Further interrogation showed the abnormal aneurysmal pancreaticoduodenal vessel, but the structure was unable to be reached given only a small network of feeding arteries measuring 1 mm or less (). No further bleeding was identified. Although the patient's condition immediately improved following embolization, there was still potential for further hemorrhage given the untreated aneurysm. Since this, after hours, treatment was prolonged with both resuscitation and procedure time, and the patient improved clinically; she was transferred to the ICU for observation and further workup. An arterial sheath was left in place for blood pressure monitoring and potential subsequent access given an incomplete interrogation of the complex anatomy. Initial management included intravenous proton pump inhibitor, placement of the nasogastric tube, and order for the serial blood counts, and a gastroenterology consult was obtained.
Later that day, the patient complained of continued epigastric abdominal pain and nausea, but vital signs remained stable. A follow-up CT scan with contrast was ordered and showed the hematoma was slightly larger containing a new bilobed 2 cm saccular area of circulating contrast. This was defined as a residual saccular pseudoaneurysm, rather than a true aneurysm, given new morphology when compared to the prior scan, and likely contained by the hematoma within the tight retroperitoneal tissues. The nearby fusiform aneurysm was not seen, presumably decompressed from rupture. The patient also required a blood transfusion given slowly dropping hemoglobin values. Although vital signs were stable, angiography was again performed given her laboratory deterioration and CT findings. The new pseudoaneurysm was identified, but unfortunately the feeding vessel remained occult after integration of multiple branches including several branches of the inferior pancreaticoduodenal artery. Given the procedure time, contrast dose, and continued relative stability of the patient, the procedure was terminated.
The vascular surgery team decided against celiac release in the acute setting given the risks of the surgery and current blood loss but agreed that a median arcuate ligament release would likely be needed as an outpatient. The patient remained stable, but there was continued suspicion for a slow hemorrhage from the ruptured aneurysm. A third mesenteric angiogram was again performed on day 2 but this time with angiography of the celiac artery and gastroduodenal artery (GDA) via the high-grade celiac artery stenosis. Using digital subtraction angiography (DSA), a prominent superior PDA branch supplying the aneurysm was identified and treated with coil embolization (Figures and ). Access from the celiac was removed, and SMA angiography demonstrated persistence of the aneurysm. Given the complexity of the PDA anatomy, cone beam CT angiography (GE Innova 540) with subsequent 3D reconstruction was performed. The 2D maximum intensity projection (MIP) images not only clearly demonstrated the PSA but also showed a second culprit posterior inferior PDA supplying the pseudoaneurysm. The gantry angle was optimized from the 3D volume rendering (), and image overlay of live fluoroscopy allowed for quick vessel selection with the microcatheter/microwire. After verification with DSA, the vessel was treated with coil embolization (Figures and ) thrombosing the PSA.
The following day, she reported feeling well with less pain and nausea. Her hemoglobin and vital signs were stable. NG was removed, and her diet was advanced. The remainder of her hospital stay was unremarkable other than hypertension treated with lisinopril, hydrochlorothiazide, and metoprolol to aid in avoiding further rebleeding events.


A 55-year-old male presented to the emergency room with complaints of worsening shortness of breath. He had contacted his physician 11 days ago complaining of low-grade fever and nasal congestion and was tested for COVID-19. On arrival to the emergency room, he was hemodynamically stable and his oxygen saturation (SpO2) was 93% on room air. Laboratory results were as shown in Table .
Chest X-ray showed patchy opacities bilaterally (Figure ).
He was started on hydroxychloroquine and azithromycin and admitted to the regular nursing floor for monitoring. Overnight, the patient started getting more hypoxic and was placed on three liters of oxygen via nasal cannula saturating about 94%. His hypoxia continued to get worse throughout the day and his inflammatory markers were uptrending (Table ). He was given one dose of TCZ 400 milligrams (mg) and intravenous methylprednisolone 60 mg once on the second day of admission and transferred to the intensive care unit (ICU) in anticipation of intubation. He was on six liters of oxygen via nasal cannula and was noted to desaturate to 81%-85% while talking. He was observed overnight and the decision was taken to hold off on intubation. The patient started improving the next day, and his inflammatory markers started trending down. He was observed in the ICU for two days and then transferred to the regular nursing floor. His liver enzymes started uptrending, and hydroxychloroquine was stopped after three days. The patient, however, received five days of azithromycin. He was discharged on the sixth day of hospitalization with home oxygen. On a one-month follow-up, the patient has been doing well and his liver enzymes are back to normal.


A 53-year-old male presented to the emergency room with complaints of shortness of breath. About 11 days ago, he started having fever, chills, fatigue, and generalized body aches. He was tested for COVID-19 six days before admission and was started on a five-day course of hydroxychloroquine and azithromycin which he completed. On arrival to the emergency room, he was found to be in mild respiratory distress and placed on five liters of oxygen via nasal cannula. He was otherwise hemodynamically stable. Laboratory results were as shown in Table .
Chest X-ray showed bilateral, predominantly peripheral and basal opacities (Figure ).
The patient was admitted to the ICU for close monitoring. The next day, he started worsening clinically, was more hypoxic, with SpO2 93% on six liters of oxygen via nasal cannula. Inflammatory markers were elevated (Table ). Intubation was being considered and the patient was given one dose of TCZ 400 mg on the second day of admission. He remained stable on six liters of oxygen via nasal cannula and was managed conservatively. After two days in the ICU, he was transferred to the regular nursing floor. He was discharged from the hospital on the seventh day with home oxygen. On a one-month follow-up, the patient has been doing well.


A 64-year-old male presented to the emergency room with complaints of fever and confusion for the last two days. His past medical history was significant for diabetes mellitus type 2, end-stage renal disease, and intermitted hemodialysis three times a week. He was tested for COVID-19 a day before admission. On admission, he had a fever of 103.1°F and was placed on two liters of oxygen via nasal cannula, SpO2 was 94%. He was otherwise hemodynamically stable and was admitted to the regular nursing floor. Laboratory results were as shown in Table .
A chest X-ray showed patchy bibasilar infiltrate, right greater than left (Figure ).
He was started on azithromycin and hydroxychloroquine. Inflammatory markers trended upwards (Table ). His oxygen requirements remained stable. He also continued to spike high-grade fevers. Given clinical worsening and uptrending inflammatory markers, he was given one dose of TCZ 400 mg on the fifth day of admission. His oxygen requirements went up on the seventh day of admission to up to four liters of oxygen via nasal cannula but improved subsequently. His inflammatory markers started trending down. He was taken off oxygen on the 10th day and discharged home on the 11th day of admission. On a one-month follow-up, the patient has been recovering well.


A 57-year-old female patient was transferred to the University General Hospital of Patras from a secondary hospital, with the diagnosis of traumatic rupture of the descending thoracic aorta, after a high-velocity motor vehicle collision with two dead passengers on the site of the accident.
On the primary survey, she had airway patency, her breathing rate was 29 per minute, her oxygen saturation was 96% with the use of oxygen supplementation, she had 89 beats per minute, and her blood pressure was 115/70. She had a good level of consciousness, and her Glasgow Coma Scale was 15/15. Clinical examination showed bilateral tenderness over her anterior chest wall, with subcutaneous emphysema on the left, tenderness over her cervical and thoracic spine, as well as over both her scapulas and right humerus, and forearm fractures. She had no abdominal tenderness. She did not have any focal neurologic deficits. She had a chest tube on the left with small drainage of bloody fluid. From her routine laboratory tests on admission, her hemoglobin and hematocrit values were 8.1 g/dl and 23.4%.
The patient's medical history included an angioplasty for myocardial infarction one month ago, and she was under dual antiplatelet and b-blocker therapy.
She was immediately transferred into the operating theatre where she was subjected to endovascular repair of the traumatic aortic rupture. The operative findings were traumatic rupture of the descending aorta distal to the origin of the left subclavian artery, at the location of the aortic isthmus, with mediastinal hematoma and bilateral pleural effusion. A GORE TAG Thoracic Endograft with Active Control System (31 mm proximal, 26 mm distal) was placed through the right common femoral artery. The proximal edge of the endograft was placed distal to the left subclavian artery (zone 3). Intraoperative angiography demonstrated a good endograft position without endoleak and with the normal angiographic appearance of the left subclavian artery. Postoperative computed tomography confirmed these findings and also showed bilateral lung contusions with pleural effusion and multiple rib fractures, left pneumothorax with subcutaneous emphysema, bilateral scapula fractures, T4 spinal body fracture, multiple cervicals, and thoracic spinal transverse process fractures and minor injury of the superior splenic pole with small amount of free intra-abdominal fluid and suspicion of pseudoaneurysm in peripheral locations of the superior splenic pole. She was transferred to the Intensive Care Unit where she remained hemodynamically stable. Repeated computed tomography scan after 2 days showed good endograft position without endoleak, while no pseudoaneurysm suspicion of the superior splenic pole was raised in this exam (Figure ). After she remained intubated for 10 days in the Intensive Care Unit, she was transferred to the cardiothoracic department from where she was discharged in good condition 12 days later, after repeated consultations from general surgeons, neurosurgeons, orthopedic surgeons, infectious diseases specialists, and psychiatrists. After one year of follow-up with CTA at 3, 6, and 12 months, the patient remains in excellent clinical condition.


An apparently healthy 13-year-old male was admitted in the emergency department with symptoms of palpitations, muscle pain, tremors, and headache of 3-h duration. He denied fever, diarrhea, vomiting, or ingestion of any kind of drug. On physical examination, the patient had a good general condition, with height and weight on the 50th percentiles for age and gender. He was euvolemic, pale, and sweating. Cardiac auscultation revealed the presence of rhythmic tachycardia without murmurs or friction, and there was tachypnea without added bruises. He also presented weakness of the lower limbs and distal hand tremor. There were no skin lesions or edema.
Multiple medical results and 16 discharge reports from different hospitals were provided by the parents. The current clinical symptoms started when he was 10 years old and since that time he had had many recurrent episodes of severe hypokalemia that had led to frequent hospital admissions, one of them in the intensive care unit due to long QT syndrome (LQTS). Many diagnoses had been ruled out, e.g. familial hypokalemic periodic paralysis, by specific genetic testing.
The patient had a medical history of previous episodes of allergic asthma with sporadic use of terbutaline, gastritis due to H. pylori, sinus tachycardia, surgical correction of strabismus, appendicectomy, and a high-flow priapism secondary to arteriovenous fistula that had been treated with selective arterial embolization when he was 6 years old. Importantly, the medical team was informed that some years previously, as a consequence of unexplained detection of benzodiazepines in the patient’s blood, custody of the child had been temporarily withdrawn from the mother.
Amazingly, the minor behaved as an adult. He had the role of interlocutor with the medical team and his comments were full of medical vocabulary that showed technical knowledge that did not correlate well with his age.
Blood analysis at admission showed the following values: hemoglobin 12.3 g/dL, leukocytes 11.68×109/L, sodium 142 mmol/L, potassium 2.4 mmol/L, chloride 101 mmol/L, urea 4 mmol/L, creatinine 53 µmol/L, glomerular filtration rate (Schwartz formula) 112 mL/min/1.73 m2, glucose 5.6 mmol/L, transtubular potassium gradient 4.9, venous blood acid-base equilibrium pH 7.33, and HCO3
- 24.5 mmol/L. Urinalysis showed pH 6.5, sodium 162 mmol/L, potassium 38 mmol/L, urea 388 mmol/L, creatinine 22.8 mmol/L, urine osmolality 982 mOsm/kg, and fractional potassium excretion 36.8%. Proteinuria and hematuria were not observed. Hormone analysis revealed aldosterone after 30 min rest of 0.06 nmol/L and urinary aldosterone of 7.0 nmol/24 h. ECG showed sinus tachycardia of 120 bpm and a QT interval of 460 ms (max 440 ms). Renal ultrasound was normal and did not show lithiasis or nephrocalcinosis.
The treatment strategy consisted in intravenous potassium replacement, reaching normal potassium plasma levels after 12 h of parenteral infusion, with no need for further potassium supplements to maintain stable potassium levels in blood after discontinuation of parenteral infusion.
Two days after admission the patient was not receiving any potassium supplement or pharmacological treatment. He was asymptomatic and had potassium levels of 4.4 mmol/L in his 8:45 a.m. blood test. Suddenly he complained of intense headache, distal tremor, and tachycardia, and a second blood test performed at 2:15 p.m. revealed that the serum potassium level had decreased to 3.4 mmol/L. Thereafter, over a 2-h interval and without any specific treatment, the symptoms gradually disappeared and the patient was then discharged with oral potassium supplements.
Given the combination of transient and recurrent severe hypokalemia and rapid response to first-line treatment, as well as the presence of clinical signs suggestive of adrenergic crisis, a possible overdose of β-adrenergic agonist drugs was suspected. The two blood samples obtained on the day of discharge were analyzed at the Catalonian Antidoping Laboratory. Plasma salbutamol levels of 3 ng/mL and 65 ng/mL were present in the 8:45 a.m. and 14:15 p.m. blood samples, respectively [reference range for peak plasma concentration after 0.04-0.1 mg inhaler dose = 0.6-1.4 ng/mL. These findings confirmed the diagnosis of hidden abuse of β-adrenergic agonists in the context of a possible factitious syndrome.


A 39-year-old female presented to a metropolitan tertiary hospital with a 1 week history of irritated and red eyes, with no associated eye pain or altered visual acuity. On further inquiry, 1 month prior to presentation she developed an episode of sinusitis and nasal crusting/erosions involving her nasal septum and left nostril. This was managed by her General Practitioner with a 5 day course of oral antibiotics (amoxicillin and clavulanic acid) and 7 days of 50 mg prednisolone daily. Her nasal erosions improved however her nasal congestion continued. She also had a 1 month history of fatigue and migratory arthralgias involving her wrist. There was no cough, dyspnoea, fever, night chills or weight loss.
Her past medical history was significant for previous TB infection. She had been treated in 1996 for pulmonary TB with a four drug regimen (2RHEZ/10RH), and in 2005 with a five drug regiment (2RHEZS/13HRZ) after being investigated for cervical lymphadenopathy. Subsequent to these treatments her TB was reported to be quiescent. Previous chest x-rays had showed bilateral apical calcified nodules.
The patient was born in India and moved to Australia in April 2017.
On examination she had bilateral conjunctival injection with normal visual acuity and extraocular eye movements. There were no rashes, no lymphadenopathy, no active synovitis, and no nasal lesions. General examination was unremarkable.
Blood tests showed elevated inflammatory markers with a C Reactive Protein of 72 (< 5 mg/L) and an Erythrocyte Sedimentation Rate of 104 (1-20 mm/hr). She had an eosinophilia of 1.6 (< 0.5X 10^9/L). PR3-ANCA was positive at 21 (< 2 U/ml).
Urine microscopy demonstrated an active urinary sediment with blood, protein and leucocytes detected. Albumin:creatinine ratio was elevated at 22.8 (< 3.5 mg/mmol) with a normal serum creatinine.
A chest X-Ray (CXR) confirmed new lesions within multiple lobes. A subsequent CT chest demonstrated multiple irregular calcified nodules in both lungs, with cavitation in a nodule in the right upper lobe (Fig. ). A further nodule in the left upper lobe demonstrated adjacent cortical irregularity involving the rib. There was evidence of thoracic calcified lymphadenopathy.
Three separate samples of induced sputum were sent for microscopy, culture and sensitivities. This was negative with no acid fast bacilli seen. Bronchoscopy was considered but not performed due to the availability of CT guided lung biopsy at the centre. This enabled direct sampling of the lung lesions which would have a greater diagnostic yield over bronchoscopy. Numerous samples were obtained from multiple lesions to provide optimal tissue to investigate the differential diagnoses. This was done as a staged procedure by an experienced chest radiologist. From the left upper lobe lesion two fine needle aspirates and two core biopsies were performed. From the right middle lobe lesion two fine needle aspirates and three core biopsies were performed. Histopathological analysis demonstrated necrotising granulomatous inflammation with adjacent eosinophil-rich interstitial inflammation, organising pneumonia and sclerosis. No suppuration, infective organisms or definite vasculitis was identified. The fine needle aspirate samples were sent for cell block and microscopy, culture and sensitivities (MCS). No acid fast bacilli, fungi or pyogenic organisms were identified on special stains (Ziehl-Neelsen, Fite, PAS + D, Methenamine silver and Gram). Direct molecular testing by polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis complex DNA on the left upper lobe FNA sample.
From these investigations it was concluded that GPA was the most likely diagnosis given the negative sputum and core biopsy microscopy, clinical history of extended TB treatment and location of pulmonary nodules. The positive TB PCR was felt to be reflective of the previously treated TB rather than active infection.
The patient was induced with IV methylprednisolone (500 mg for 3 days) and two doses of rituximab (1 g two weeks apart). Cyclophosphamide was considered but decided against due to fertility concerns. She was then continued on oral prednisolone at 50 mg daily with a weaning regimen. On ophthalmological review her eye symptoms were attributed to a marginal keratitis and treated with fluorometholone eye drops.
Following her initial induction treatment the patient had a good clinical response with improvement in her sinus and joint symptoms. CT chest at 3 months showed interval improvement with decrease in size multiple previous pulmonary masses and right upper lobe cavitation. Given a decreased Thiopurine methyltransferase (TPMT) level and thus mycophenolate was chosen over azathioprine as a steroid sparing agent. She had complete peripheral B cell depletion and normalisation of her PR3 within 4 months and her prednisolone dose was weaned down to 10 mg within 6 months of starting treatment. At 11 months after rituximab therapy she had B cell recovery associated with positive PR3-ANCA at 15 U/ml and clinical relapse with recurrence of ocular symptoms with uveitis and enlargement of pulmonary nodules on CT. Her corticosteroid dose was increased and she was retreated with 2 g of rituximab with resolution her ocular symptoms, normalisation of PR3-ANCA with interval improvement on CT and she remains under regular clinical review.
Her urine protein:creatinine ratio increased to 324 (< 13 mg/mmol) before stabilising at 60 mg/mmol with a normal renal function.


An 82-year-old female patient had history of hypertension under medication for several years, and she presented to out-patient department in Feb., 2018 with 10-year-duration of palpable tumor on left breast which was in rapid growth in recent months. Otherwise, no dyspnea, bone pain, or headache were noted. Lab data showed WBC: 14500/μL, hemoglobin: 9.2 g/dL, alkaline phosphatase: 689 U/L, and CA-153: 65.6 U/ml. Computerized tomography of chest and abdomen showed no lung or liver metastasis (Fig. ). Whole body bone scan showed no bony metastasis. Total mastectomy of left breast was performed thereafter (Figs. , and ). The excised specimen consisted of a large and firm oval mass partly covered by an elliptical skin, measuring 30 × 26 × 20 cm, weighed 4400 g. Pathology microphotograph revealed overgrowth of a diffused hypercellular tumor in stroma of breast tissue with nuclear atypia and mitoses indicating malignant phyllodes tumor of breast. High mitosis activity (10/10 HPF) and tumor necrosis were found (Fig. ). However, the tumor free margin was less than 1 cm. Adjuvant radiotherapy was suggested while she declined out of personal reasons.
The patient had two local regional recurrent tumors over left chest wall 2 months later (Apr., 2018), and she underwent local excision then. She was subsequently followed by image guided radiotherapy with 5040 cGy/28 Frs since then. After completing whole course of radiotherapy, she was lost followed up.
It’s not until 6 months later (Nov., 2018) her suffering from local recurrent tumors over left chest wall again that she came to out-patient department for help where scheduled excision of breast tumor was performed (Fig. ). One tumor (7x5x5 cm) was located at left para-sternal region, and the other one (3.5x3x2.5 cm) was over left sub-axillary region. On 5th day after the operation, she had symptoms of passage of tarry stool and progressing weakness. On further inquiry, she has melena for 2 weeks. Laboratory data revealed severe anemia (decreasing hemoglobin level from 8.8 to 5.4 mg/dL in 1 week). Esophagogastroduodenoscopy (EGD) revealed a prominent protruding, ulcerofungating gastric tumor with punctate bleeding at fundus (Fig. ). We performed gastrostomy with excision of the gastric tumor mentioned above due to refractory passage of tarry stool despite conservative treatment (Figs. and ). Metastatic tumor from malignant phyllodes tumor of left breast was confirmed by pathology (Fig. ). After then, she didn’t experience any bleeding events anymore. Adjuvant chemotherapy was suggested while her family declined because of old age. During the hospital course, she was diagnosed of brain metastasis due to altered personality and decreased consciousness. Under hospice care in nursing home, she ultimately died 2 months later. (Mar., 2019).


A 43-year-old female with a past medical history of diabetes and prior surgical history of a tonsillectomy and uvulectomy presented with a sudden onset of sore throat that woke her up from sleep at 3:00 am. Associated with the sore throat, she had hoarseness of her voice, difficulty breathing and felt that her throat was closing. She forced herself to vomit and then felt better. She denied any fevers or chills.
Later, the patient mentioned that she had chronic neck pain from a prior accident and had been told that she has C5-C6 stenosis. About a week prior, she had been involved in another MVC and had some neck pain after that. She had also reported to be taking lisinopril.
Pertinent physical exam findings were mild erythema of the posterior oropharynx, pain on palpation along the left lateral neck and some decreased range of motion. She was tolerating secretions, protecting her airway and no gross inflammation was noted on the exam.
Blood work revealed no leukocytosis. Soft tissue neck X-ray showed reversal of the cervical lordosis, degenerative and erosive changes at C4-C5 and C5-C6, and thickening of the prevertebral soft tissues which are shown in Figure .
She obtained a CT of the neck and cervical spine that showed osteophyte complexes at C4-C5 and C5-C6, as well as calcific tendonitis of the longus colli with a moderate amount of prevertebral free fluid (Figures , ).
Neurosurgery was consulted from the ED who recommended getting an MRI of the neck while consulting ENT as well. ENT happened to be in the ED and performed a bedside laryngoscopy that showed edema of the left arytenoid with full functionality of the vocal cords and no signs of airway compromise. The patient was started on steroids, antibiotics, H2 blockers, and the ACE-inhibitor was discontinued due to suspected angioedema by the ENT. She was also admitted to the ICU for airway monitoring.
The MRI of the neck again showed calcific tendonitis of the longus colli with moderate prevertebral fluid (Figure ). Meanwhile, the patient had complete resolution of her symptoms in 24 hours and she was cleared from both neurosurgery and ENT to be discharged.


A 72-year-old man was referred to our hospital for suspected right pulmonary effusion on chest X-ray. For approximately three years around the age of 30, he dealt with serpentine asbestos in research. Seven years before he was referred to our hospital, he visited another hospital for suspected left pleural effusion on chest X-ray, and his chest computed tomography (CT) showed left pleural effusion and ipsilateral pleural thickening; after two years of follow-up, the pleural effusion had resolved without treatment (Fig. ). Two years later, he had similar abnormalities pointed out on chest X-ray, and his chest CT revealed unchanged left pleural thickening; with no apparent change, his follow-up was finished after one year (Fig. ).
At the first visit to our hospital, there were no specific findings on physical examination as well as laboratory tests, except for slightly low serum haemoglobin level. Chest CT showed bilateral pleural thickening accompanied with calcification on the left pleura (Fig. ). Over the next four years, thickening and calcification of the pleura showed gradual progression, and accordingly his lung volumes declined (Fig. ).
During this progression, he was admitted to our hospital for acute respiratory failure caused by bacterial pneumonia. Despite resolution of pneumonia, he developed hypercapnic chronic respiratory failure, and therefore home oxygen therapy and non-invasive positive pressure ventilation (NPPV) were initiated. Subsequently, he experienced recurrent bacterial pneumonia, and 53 months since the first visit he was again hospitalized for acute-on-chronic respiratory failure. Thickening and calcification of the pleura progressed furthermore (Fig. ). Despite treatment, he died on the 94th day of admission; autopsy was performed with the consent of his family. On gross finding, the bilateral lungs were entirely covered with white, hard, and fibrous membrane and adhered to the chest wall. Microscopically, the membrane consisted of hyalinized fibrous tissue with patchy infiltration of lymphocytes. No obvious asbestos body was detected. (Fig. ) Asbestos body concentration was measured at the Kobe Rosai Hospital. Tissue samples were derived from the right lower lobe and processed using standard methods. Asbestos body concentration was 1086/g dry lung tissue, indicating moderate asbestos exposure.


A 31-year-old female presented to the emergency department in King Fahad University hospital in Saudi Arabia with dyspnea. She was found to have an elevated D-dimer in her laboratory studies. A lung perfusion scan was ordered to exclude pulmonary embolism. The scan demonstrated a normal homogeneous pattern of tracer uptake in both lung fields with no obvious areas of peripheral segmental perfusion defects noted in either of lung fields. Also, the CXR was performed and showed a bilateral small atelectatic band as well as a small left pleural effusion in addition to evidence of alveolar hemorrhage. The patient was admitted to the ICU and received 500 mg tablet of TXA orally, antibiotics, 6 units fresh frozen blood, and 1-unit RBCs; after 9 days, she was given 500 mg of TXA intravenously. The patient was diagnosed with SLE and pulmonary hemorrhage and lupus nephritis. The CXR was repeated and it showed improvement. The platelets are improved. The procalcitonin was < 2, which indicated a less likely source of infection and more likely of an inflammatory process likely of her disease. Cultures from her BAL also showed no growth. After 1 week, the patient began to have hemoptysis again. A CXR was done which showed bilateral pleural effusions with bilateral lung bases developing atelectatic changes. Additionally, there were bilateral confluent ill-defined patchy opacities in the mid and lower lung zones with a prominent bilateral central pulmonary vasculature; the computed tomography with contrast shows the pulmonary trunk and main branches with segmental and subsegmental branches appeared well-opacified without evidence of filling defect or aneurysm formation. Lung parenchyma demonstrated multiple bilateral patchy ground-glass opacities and consolidation noted throughout the lung parenchyma predominantly within the lower lobe which was not sparing the pleural surface. It was associated with a tree-in-bud appearance. The patient was started on 500 mg of nebulized TXA every 8 h for 1 day. Five days later, the patient showed improvement as evidenced by stable hemoglobin, no longer requiring more blood products, and was discharged.


Case 2 is a 14-year-old female with known case of G6PD, nephrotic syndrome, and vasculitis with low complement levels. She was admitted to our hospital because of nephrotic syndrome with microcytic hypochromic anemia for investigation with CAP. The patient developed dyspnea in which CTPA was done, and it was negative for pulmonary embolism, but it showed bilateral consolidation with bilateral mild pleural effusion and mild pericardial effusion. She had a sudden episode of headache, and CT head was ordered. During her imaging, she developed status epilepticus that needed multiple doses of lorazepam and phenytoin; then, she was intubated on mechanical ventilation, not on inotropic support. She shifted to MICU. Bronchoscopy was done which shows diffuse alveolar hemorrhage with negative cultures. The patient received 500 g TXA in 5 ml 0.9% NS through the ETT once, then nebulized 500 mg in 5 ml of 0.9% NS every 8 h for 3 days through a nebulizer; the bleeding from ETT is markedly reduced; O2 requirements reduce with reduced PEEP; the bleeding stopped whereas there is no positive/negative change on the CXR that is why there is no need to continue TXA. Otherwise, she continued TXA for one more day.


Case 3 is a 66-year-old female with known case of rheumatic heart disease since the age of 13 years complicated with AVR and MVR S/P valvuloplasty and valve replacement in 1978 and 2019; in 1998, she got CAD S/P PCI-atrial fibrillation and was on warfarin; also, she did open heart surgery 40 days back. The patient presented to the ER with shortness of breath and productive cough with hemoptysis for 1 day ago. She has dyspnea at rest with no orthopnea or PND, and no chest pain or bleeding from other sites. She also complained of right upper limb pain for 2 weeks which has worsened over the past few days associated with swelling which started yesterday, no fever, no history of contact with sick patients, and no history of thromboembolism. She was admitted to the ICU and received ciprofloxacin and 500 mg TXA through IVP; the next day, she took 100 mg of nebulized TXA every 8 h for 2 days, and bleeding was reduced over the next few days. The patient was discharged with improvement after 12 days of admission.


The proband was a 48-year-old Japanese woman with stage IV lung papillary adenocarcinoma, T4N2M1 with pleural dissemination. Despite various treatments including EGFR–tyrosine kinase inhibitors, she died as a result of progressive lung cancer within 1 year and 6 months of treatment initiation. The proband’s mother underwent lobectomy at 61 years of age for stage IA lung papillary adenocarcinoma. She is alive and disease free 22 years and 4 months after surgery. The proband’s younger brother was diagnosed with stage IA lung papillary adenocarcinoma at 41 years of age and underwent lobectomy. He is alive and disease free 9 years and 3 months after surgery. The proband’s aunt had lung cancer at 70 years of age; however, no precise data are available regarding her disease course and prognosis. The proband’s nephew had cecal non-Hodgkin lymphoma at 12 years of age and is alive and disease free after surgery and intensive chemotherapy. No other family history of malignant disease was revealed on a detailed interview ().
The study was approved by the ethics committee of the participating institutes, and written informed consent was obtained from the proband and two family members with lung cancer. Peripheral blood mononuclear cells of the proband, cancerous pleural effusion from the proband, and formalin-fixed paraffin-embedded tumor samples from her mother and younger brother were subjected to genetic analysis. Genomic DNA was extracted from these samples for next-generation sequencing (NGS) analysis using the DNeasy Blood & Tissue kit (Qiagen, Hilden, Germany).
We performed WGS using genomic DNA extracted from cancer cells harvested from the cancerous pleural effusion and compared it to that of whole blood. Paired-end sequencing was performed using Illumina’s NGS platforms HiSeq X Ten system (Illumina, San Diego, CA). Sequence reads were aligned against the reference human genome (hg19) with Burrows-Wheeler Aligner. Single-nucleotide variants and insertions/deletions in cancer tissue and normal blood genomes were identified using GATK and SomaticSniper. Copy number variations were analyzed using Control-FREEC. Structural variations identified using both BreakDancer and Pindel were further analyzed. We adopted driver gene mutations registered in the Catalogue of Somatic Mutations in Cancer (COSMIC) database, predicted functional consequences using SIFT and PolyPhen-2 software, or categorized them as pathogenic or likely pathogenic per the ClinVar database. Furthermore, we examined known causative germline mutations of hereditary cancers and somatic mutations of major cancer-related genes among the gene alterations in the proband.
For TS analysis, we used the Ion AmpliSeq Custom Panel and Ion Torrent PGM deep sequencing Ion AmpliSeq Cancer Hotspot Panel v2 (Thermo Fisher Scientific, Waltham, MA). Barcoded libraries were pooled and sequenced on Ion 318 Chip using Ion Torrent PGM in accordance with the manufacturer’s instructions. We examined mutations in 50 cancer-related genes in tumor DNA derived from the proband and two of her family members.
WGS revealed the previously reported germline EGFR V843I mutation; however, no other germline oncogenic mutations were observed in the peripheral blood and cancerous pleural effusion of the proband. Furthermore, WGS revealed a de novo TP53 R248W somatic mutation in addition to a second EGFR mutation, L858R, in the cancer cells of the proband. The EGFR V843I and L858R mutations and the TP53 R248W mutation have been registered in the COSMIC database as functional mutations per the SIFT and PolyPhen-2 software. In the ClinVar database, the EGFR V843I mutation has been registered as likely pathogenic, and the TP53 R248W mutation is pathogenic. Other genetic abnormalities, including insertions/deletions, copy-number variations, and structural variations of cancer-related genes, were not detected in blood or cancer cells of the proband ( and ). TS analysis of mutations in 50 cancer-related genes revealed the same mutations as those confirmed via WGS analysis of cancer cells of the proband. In contrast, only the EGFR V843I and L858R mutations were identified in tumors in the mother and brother of the proband. TP53 mutations including R248W identified in cancer tissue of the proband were not detected in that of her mother and brother ().


Patient I was a 73-year-old man who experienced right shoulder pain for >2 months without any history of trauma. His pain progressively worsened with a waxing and waning course, despite use of nonsteroidal anti-inflammatory drugs and supportive physical therapy. There was no obvious improvement after injection of intra-articular corticosteroids from another hospital in the previous month. He subsequently experienced limitation of activities of daily living and night pain that worsened over time and made it impossible to sleep at night. Shoulder pain on the Visual Analogue Scale (VAS) was 5 at rest and 7 during motion. There was no history of trauma, known chronic diseases, or alcohol and drug abuse.
On physical examination, the skin over the shoulder joint was normal, and gentle palpation around the shoulder joint did not elicit pain. There was no loss of passive motion of his shoulder joint. However, the empty-can, Neer, and Hawkin's tests were positive. All laboratory results were within normal limits. Plain radiographs revealed a hooked acromion in the supraspinatus outlet view. US revealed marked SASD bursal effusion with a full-thickness tear of the supraspinatus tendon (Fig. A). To ensure an accurate diagnosis, he underwent magnetic resonance imaging (MRI) that revealed a full-thickness tear along the supraspinatus tendon with SASD bursitis.
Because the symptoms failed to resolve with conservative management, including corticosteroid injection, the authors attempted to aspirate fluid from the SASD bursa to the greatest extent possible (Fig. B). Under US guidance, 8 mL of clear bursal fluid was aspirated, and the specimen was sent for analysis. US-guided intra-articular corticosteroid injection was administered by penetrating the posterior joint capsule. A mixture of 0.5% lidocaine and 40 mg triamcinolone was injected into the shoulder joint space by visualizing the posterior intra-articular space.[ Distension of the joint cavity and SASD bursa after injection was checked to confirm that the procedure was accurate.
Bursal fluid analysis revealed normal white cell counts without crystals. Acid-fast bacillus stain and gram stain were negative. Fluid culture grew no microorganisms.
After aspiration and intra-articular injection, the symptoms abated. One month later, his pain score on VAS decreased from 5 to 2 at rest and from 7 to 3 during motion. Upon recheck 2 months after the combined procedure, patient I was satisfied with the pain relief; therefore, surgical management was not indicated.


Patient II was a 65-year-old man who experienced right shoulder pain for >1 month with no history of trauma and known left-sided weakness after right cerebral infarction 15 years before. He complained of unbearable pain despite corticosteroid injection 3 weeks before. Subjective pain on the VAS was 7 at rest, 9 during motion. On physical examination, empty-can and Hawkin's tests were positive. US demonstrated substantial effusion of the long biceps tendon and SASD bursa with a full-thickness tear of the supraspinatus and a partial thickness tear of subscapularis tendon. He did not want MRI for economic reasons. Under US guidance, 7 mL of the clear bursal fluid was aspirated, and a triamcinolone mixture was injected in the same way. All laboratory results, including bursal fluid, were within normal limits. Compared with the scores after 1 month, his pain score on the VAS slightly decreased from 7 to 4 at rest, from 9 to 6 during motion. Although pain abated, an additional 3 mL of bursal fluid was aspirated, and triamcinolone injected again. Upon review 3 months after the repeat procedure, his pain score on the VAS decreased from 4 to 2 at rest, from 6 to 4 during motion.


Patient III was a 70-year-old man who experienced right shoulder pain for >3 months with no history of trauma. There was no noticeable improvement following intra-articular corticosteroid injection 1 month before. Subjective pain on the VAS was 5 at rest and 8 during motion. On physical examination, the empty-can test was positive. US demonstrated substantial effusion of the long biceps tendon and SASD bursa with a full-thickness tear of the supraspinatus and subscapularis tendon (Fig. C). MRI revealed a full-thickness tear along the supraspinatus and subscapularis tendon with SASD bursitis. With US guidance, 9 mL of clear bursal fluid was aspirated, and a triamcinolone mixture was injected. All laboratory results, including bursal fluid levels were within normal limits. At 1 month, his pain score on the VAS decreased from 5 to 3 at rest and from 8 to 4 during motion; follow-up US revealed diminution of the previously noted bursal distension (Fig. D). His pain scores at 2 months were approximately at the same level as that at 1 month; follow-up US revealed increased bursal distension compared to the previous US finding but fluid accumulation was slightly decreased compared to the initial US finding (Fig. E).


A 54-year-old woman who was morbidly obese (weight: 150 kg, height: 1.6 m, body mass index: 58.59) and had type 2 diabetes mellitus presented to emergency room with abdominal pain and symptoms of intestinal obstruction. The computed tomography (CT) scan showed sigmoid cancer with multiple bilateral liver metastases (one involved the right and middle hepatic vein). She then underwent an emergency sigmoidectomy (pT4N0M1, triple wild type K-RAS, N-RAS and B-RAF), and received ten cycles of FOLFIRI-CETUXIMAB. The liver metastases partially responded, as seen with a CT and positron emission tomography (PET) scan. The FLR was 480 cc, representing 30.3% of the total liver volume, and the FLR/BW ratio was 0.31. The FLR was clearly insufficient and the patient was also candidate for surgical weight loss. After discussing the case in a multidisciplinary committee and obtaining written informed consent by the patient, we decided to perform a T-ALPPS procedure combined with a simultaneous sleeve gastrectomy with interstage chemotherapy.
The T-ALPPS technique was performed as described previously.[ We cleaned the FLR, occluded the portal vein, and placed the tourniquet. Finally, we performed a sleeve gastrectomy. The macrovesicular steatosis in the liver specimen was around 50% (Fig. D).
The post-operative course was uneventful, and the patient was discharged on the 5th post-operative day. Nine cycles of interstage chemotherapy were administered according to the same pre-operative scheme, and there was no disease progression during this time. Six months after the first stage of T-ALPPS, the FLR increased by 68.8% to 810 cc (Fig. A), and the patient lost 59.3% of the excess weight (51 kg; Fig. B). Further, the FLR / BW ratio was 0.82 (Fig. C). Next, the second stage of the T-ALPPS procedure was performed by completing the right trisectionectomy. The liver steatosis in the specimen after the second stage decreased to between 1% and 10% (Fig. E). The only post-operative complication was a transient increase of INR treated exclusively with vitamin K. The patient was discharged on the 12th post-operative day. Adjuvant chemotherapy was not administered and actually, four months after the second stage, the patient is alive without recurrence.


A 40-year-old woman was admitted to our hospital for rapidly progressive cognitive decline for 15 days and left limb weakness for 5 days. She was diagnosed with cerebral hemorrhage in the local hospital and treated with mannitol (125 mL q8 h). However, her symptoms aggravated and she became drowsy and refused to eat.
On physical examination, she showed lethargy, disorientation and memory impairment, left limb weakness, and positive Babinski sign. Enlargement of the spleen and liver was detected on abdominal palpation.
Laboratory testing showed a leukocyte count of 20.7 × 109/L (normal level, 4.0–10.0 × 109/L) and a platelet count of 531 × 109/L (normal level, 100–300 × 106/L). Tumor marker testing showed an elevated neuron-specific enolase level of 47.8 ng/mL (normal level, <25 ng/mL). Antineutrophil cytoplasmic antibody, antinuclear antibody, and other autoimmune antibody levels were normal. Prothrombin time level was 15.6 seconds (normal level, 12.0–14.0 seconds), and activated partial thromboplastin time was 59.2 seconds (normal level, 30–45 seconds) Lumbar puncture was performed and intracranial pressure was found to be 200 mmH2O; the protein level in the cerebrospinal fluid was 104.10 mg/dL (normal level, 8–43 mg/dL). Brain magnetic resonance imaging (Fig. A and B) indicated right thalamic and occipital hemorrhage and edema. Magnetic resonance venography (Fig. F) showed thrombosis of the parieto-occipital segment of the superior sagittal sinus, right transverse sinus, sigmoid sinus, internal jugular vein, and left transverse sinus vein. Therefore, she was diagnosed with CVT and multiple intracranial hemorrhage. Furthermore, an abdominal computed tomography with contrast was performed and it showed a giant spleen, portal hypertension, a small amount of hydrocele fluid in the abdomen and pelvis. In addition, magnetic resonance spectroscopy focusing on the right thalamic (Fig. C) lesion reported an increased lipoprotein level and a normal cholesterol level, indicating necrosis instead of tumor development.
Because the patients had multiple systemic conditions, she underwent whole-exome sequencing, which showed a mutation in JAK2 V617F. Bone marrow puncture was subsequently performed, and the cytological examination revealed myeloid hyperplasia with increased neutrophils alkaline phosphatase rate while bone marrow biopsy showed hematopoietic hyperplasia and reticular fiber hyperplasia.
The patient was eventually diagnosed as showing CVT accompanying multiple intracranial hemorrhage with JAK2 V617F positive PMF. She received treatment with low-molecular-weight heparin sodium 3800 IU twice a day. One week later, she showed a significant improvement in symptoms and was discharged with continued oral anticoagulant therapy. Follow-up brain magnetic resonance imaging scans at 4 (Fig. D) and 9 months (Fig. E) showed a reduction signal in the right thalamic and occipital lobe lesion. The patient showed full recovery from limb weakness. As for her cognitive, the patient herself said she did not feel any change in her memory and was able to continue her work as usual, and the family number did not notice any change in her personality or behaviors.