A 27-year-old woman with underlying VSD presented to a local hospital with sudden onset of cough and pleuritic chest pain. The patient was intubated in the emergency department because of tachycardia, tachypnoea and severe dyspnoea. Her vital signs revealed a blood pressure of 98/78 mmHg and a heart rate of 130 bpm, and she was afebrile. Physical examination showed a continuous murmur on auscultation of the anterior chest wall.
An electrocardiogram showed sinus tachycardia and ST depression in leads V4-V6. A chest X-ray revealed severe lung congestion and cardiomegaly. Transthoracic echocardiography (TTE) showed a ruptured SVA connecting to the right ventricle (RV), a subarterial VSD measuring 10 × 12 mm, with a left ventricular ejection fraction of 47% and normal valve function with mild tricuspid regurgitation (). No clot or vegetation was observed. Blood tests revealed a white blood cell count of 31 000/L, serum creatinine of 321 μmol/L, aspartate aminotransferase of 5199 U/L and alanine aminotransferase of 3458 U/L. The patient was diagnosed with ruptured SVA with VSD in cardiogenic shock and transferred to our hospital for further management.
An emergency operation was planned. However, just before the operation, the patient sustained a cardiac arrest secondary to cardiogenic shock. She was revived after 7 min of cardio-pulmonary resuscitation (CPR), supported with high doses of inotropes, i.e. intravenous noradrenaline at 0.3 μg/kg/min, adrenaline at 0.15 μg/kg/min, vasopressin at 3 unit/h, and dobutamine at 20 μg/kg/min. Because of the patient’s rapidly deteriorating condition, a multidisciplinary team conference was held, and a high-risk informed consent was obtained from the patient’s family for an emergency operation.
After sternotomy, cardiopulmonary bypass (CPB) was established with ascending aortic and bicaval cannulations, and systemic cooling lowered the body temperature to 32°C. The aorta was cross clamped, and an oblique aortotomy was performed. Antegrade cardioplegia was delivered into the coronary ostia with left ventricle venting via the right superior pulmonary vein. After arresting the heart, the ruptured SVA was identified by a thorough inspection (). There was no vegetation. The main pulmonary artery was opened with a vertical incision, and the VSD was found just below the aortic annulus.
Subsequently, repair of the SVA and VSD closure were completed with two separate Gore-tex® 0.4 mm patches. The patient was rewarmed and weaned off CPB with high dose inotropic support. Postoperative transoesophageal echocardiogram showed no residual shunt or aortic regurgitation, and the patient was transferred to the intensive care unit. The aortic cross-clamp time, CPB time, and total operative times were 54, 119 and 293 min, respectively.
Postoperatively, the patient required prolonged intensive care. Inhaled nitric oxide for 3 days and continuous veno-venous hemofiltration for 10 days supported the patient and significantly improved blood parameters, which gradually normalized in the following days. A postoperative TTE revealed no shunt or aortic regurgitation (). However, a tracheostomy was performed on postoperative day (POD) 15 because of prolonged ventilation. The patient was discharged on POD 55 in a stable condition after de-cannulation of the tracheostomy tube.


A 78-year-old caucasian male was referred to our hospital to evaluate expansion of an abdominal aortic aneurysm (AAA) 4 years after endovascular aortic repair (EVAR). At presentation, the patient was suffering from abdominal pain but denied chest pain or dyspnoea. His past medical history includes arterial hypertension, hypercholesterolaemia, and smoking. Initial vital signs were blood pressure 170/87 mmHg, heart rate 97 beats/min, oxygen saturation 97%, respiratory rate 24/min, and temperature 36.5°C. Physical examination did not reveal any abnormal heart or vascular murmurs. Laboratory testing was within normal range.
Computed tomography angiography showed a rapid expansion of the AAA from 62 × 60 mm to 67 × 60 mm in 1 year and up to 69 × 62 mm in the 2 weeks prior to hospitalization, attributed to a type V endoleak (). Computed tomography angiography incidentally revealed a giant CAA of the right coronary artery with cross-sectional diameters up to 5 × 4 cm (). Coronary angiogram confirmed the CAA () and showed highly significant stenoses at the entrance and the exit of the coronary aneurysm, with good flow (wash-in and wash-out) and no evidence of significant parietal thrombus (Video 1). The left coronary system was ectatic without significant stenosis (). Ventriculography demonstrated a preserved ejection fraction of 60% without regional wall motion abnormalities. Given the patients’ age, cardiovascular risk factors and history, an atherosclerotic aetiology was assumed and screening for cerebral aneurisms was not performed.
After interdisciplinary discussion (heart team together with vascular surgeons), the patient underwent urgent EVAR explant and aorto-bi-iliac bypass grafting first (). He recovered well from the surgical procedure and had an uneventful postoperative course. In a second step, the CAA was excised, and CABG of the right coronary artery was performed. Histological analysis of the aneurysmal wall was in line with an atheromatous aetiology of the CAA. Based on the patients’ history and the histological analysis, there was no evidence of an underlying systemic disease causing the aneurysms. Sixteen months after surgery, the patient was asymptomatic with good exercise tolerance.


A 24-year-old woman presented with a palpable painless mass in the left thyroid lobe. The mass had initially appeared 2 months previously. The patient had no swallowing discomfort, hoarseness, palpitation, shortness of breath, or other clinical manifestations. Her physical examination findings and laboratory test results were normal.
Conventional US examination revealed an anechoic tumor with numerous linear echogenic septal lines in the ventral left thyroid lobe. The tumor had a three-dimensional size of 36 × 12 ×15 mm (). Unusual internal flow was captured by color Doppler flow imaging (CDFI) of the tumor, which presented a vein-like velocity curve with blood flowing into the left inferior thyroid vein. The tumor significantly shrank when compressed with the ultrasound probe (positive compression test), but no significant increase in blood flow was observed by CDFI (). No other abnormalities were detected in the bilateral neck. No lymph node enlargement was found.
CEUS showed obvious enhancement of the thyroid at 11 s with subsequent perfusion of the tumor at 13 s after intravenous administration of a contrast agent (SonoVue; Bracco, Milan, Italy). The tumor exhibited slightly inhomogeneous enhancement compared with the surrounding thyroid tissues, and twisted vessels were detectable within the tumor (). The tumor significantly shrank when compressed by the US probe (). Once the probe was released, the tumor showed rapid filling of contrast agent and high enhancement (). Contrast enhancement had almost subsided in the surrounding thyroid tissue at 5 minutes 14 s after injection, while the tumor still exhibited enhancement (). The time intensity curve showed the typical “slow in and slow out” enhancement pattern (). Based on the combined findings of routine US and CEUS, our initial diagnosis was thyroid venous hemangioma.
A computed tomography examination was performed to validate our initial diagnosis. Unenhanced images showed left thyroid lobe enlargement and uneven low-density lesions within the gland. The lesions measured about 16 × 15 mm in the axial image and had an unclear boundary with the surrounding thyroid tissue (). In the arterial phase after intravenous administration of contrast agent, the lesions exhibited moderately inhomogeneous enhancement that was inferior to the enhancement of the surrounding thyroid tissues ().
Postoperative pathologic examination showed numerous proliferative vessels within the lesion; multiple irregular, dilated vessel lumens filled with red blood cells; and multiple hemorrhagic zones (). Immunohistochemistry showed CD31 positivity for proliferative vessels (representative staining images are shown in ); D240 negativity, fli-1 positivity, CD34 positivity, and smooth muscle actin positivity (representative staining images are shown in ); and Ki67 positivity. These pathological results finally confirmed the initial diagnosis of thyroid vein hemangioma.


A 62-year-old African-American woman presented to the emergency department with a 3-day history of RUQ pain, decreased oral intake, and non-bloody, non-bilious emesis. Vital signs were within normal limits, and physical examination was notable for moderate tenderness in the RUQ with a positive Murphy’s sign. There was no guarding, rebound tenderness, nor hepatomegaly. Past medical history was significant for hypertension, hyperlipidemia and diabetes mellitus. Laboratory results were notable for total bilirubin of 5.80 mg/dL (reference: 0.30 - 1.00 mg/dL), alkaline phosphatase of 426 U/L (reference: 34 - 104 U/L), aspartate aminotransferase (AST) of 663 U/L (reference: 13 - 39 U/L) and alanine aminotransferase (ALT) of 703 U/L (reference: 7 - 52 U/L). Lipase was within the reference range. Basic metabolic panel (BMP) was remarkable only for glucose of 343 mg/dL (reference: 70 - 99 mg/dL). Hemogram parameters were within their respective reference ranges, and there was no leukocytosis. Lactate was 3.0 mmol/L (reference: 2 - 4 mmol/L), and the patient was markedly alkalotic with a venous pH of 7.62. An ultrasound of the RUQ revealed a distended gallbladder with heterogeneous echogenicity of unclear etiology, along with intrahepatic and common bile duct dilatation.
Upon admission, a magnetic resonance cholangiopancreatography revealed debris and stones (about 1 cm) and two irregular septate nodules (about 1.5 cm) in the inferior fundus of the gallbladder (). Multiple gallstones were also seen. The common bile duct measured 11 mm in diameter and was noted to be filled with debris. Endoscopic retrograde cholangiopancreatography revealed thick sludge obstructing the ampulla of Vater and was extracted with a balloon sweep, followed by placement of a stent in the common bile duct. On hospital day 7, a laparoscopic cholecystectomy was started and was converted intraoperatively into an open cholecystectomy due to severe gallbladder distention. The post-operative course was uneventful, with gradually resolving abdominal pain, and the patient was discharged the following day.
Gross examination of the resected specimen showed an exophytic mass (5 × 4 × 2 cm) located at the fundus of the gallbladder (). Histopathologic examination of the mass showed a neoplasm consisting of three distinct components. An infiltrating SCC (60%) and an adjacent NEC (30%) were observed (). The squamous component showed moderate differentiation with areas of keratinization (). The neuroendocrine component showed areas of necrosis; the neuroendocrine cells had moderate cytoplasm, inconspicuous nucleoli and “salt and pepper” chromatin, with numerous mitotic figures (). A third adenocarcinoma component comprised about 10% of the neoplasm (). The tumor infiltrated the muscularis propria into perimuscular connective tissue.
The SCC was positive for p40 (), p63 and CK7; the neuroendocrine component was positive for synaptophysin () and chromogranin; and the adenocarcinoma component was positive for CK7 () and mucin by mucicarmine, but negative for p40 and p63.
Because of these findings, the patient was readmitted for a partial hepatectomy of segments IVb and V of the liver along with lymph node dissection for staging. Histopathologic review of the partial hepatectomy, perihepatic lymph nodes and portal lymph nodes was negative for malignancy; the patient’s tumor was classified as stage IIA. The patient was started on eight cycles of leucovorin, oxaliplatin and 5-fluorouracil (5-FU).
Three months later, a positron emission tomography (PET) scan revealed hypermetabolic enlarged portacaval lymphadenopathy and a hypermetabolic soft tissue nodule in the anterior abdomen to the left of the umbilicus, suggesting metastatic disease. Biopsy of the nodule showed a poorly differentiated carcinoma that was positive for p63 and negative for synaptophysin supporting squamous differentiation and consistent with metastasis.
The patient is alive and well at 14 months after the initial diagnosis.
Since the behavior of gallbladder tumors with mixed neuroendocrine and non-neuroendocrine components is not well documented, we reviewed the literature for these mixed tumors (two or three components). We searched PubMed and Google Scholar for “mixed gallbladder tumor”, “mixed gallbladder carcinoma”, “composite gallbladder tumor”, “composite gall bladder carcinoma”, “adenocarcinoma of the gallbladder”, “squamous cell carcinoma of the gall bladder”, “neuroendocrine carcinoma of the gallbladder” and “neuroendocrine tumor of the gall bladder”. We found 15 cases of mixed gallbladder neoplasms with two-component (NEC and adenocarcinoma) and eight cases with three-component (NEC, SCC and adenocarcinoma) neoplasms (
.
The patients with two-component tumors presented at a mean age of 58 years (range: 45 - 85 years) and the male/female ratio was 1:2. Most of the patients presented with generalized abdominal pain and some with pain localized in the RUQ. Other symptoms included jaundice (2/22), fever (1/22) and weight loss (2/22). Gallstones were documented in 11/22 patients. The mean size of the tumor was 6 cm (range: < 1 - 15 cm); it was located in the gallbladder fundus in 7/22, and the body in 3/22 patients. In four patients, the tumor occupied more than one anatomic region of the gallbladder, and in four patients, the tumor extended beyond the gallbladder to involve the liver, pancreas or duodenum. The NEC component of the tumor was composed of large cell NEC in 13/22 patients and of small cell NEC in 6/22 patients. One patient had both large cell and small cell NECs, and another had a grade 2 NEC. Five patients presented with metastasis to regional lymph nodes and another three to other viscera. In one series of cases, three patients had metastasis of only the neuroendocrine component, and one patient had metastasis of both the neuroendocrine and adenocarcinoma components. The adenocarcinoma was classified as well differentiated in four patients, and as papillary adenocarcinoma in two patients []. Cholecystectomy was performed in 14/22 patients with additional partial hepatectomy in 8/22 patients, and chemotherapy in five of these. A combination of carboplatin and etoposide was used in two patients and a combination of cisplatin and etoposide in another two. Details of chemotherapy for the fifth patient are not available. A somatostatin analogue was used in three of the five patients on chemotherapy. The patients without liver invasion or metastases were disease-free for a mean of 14.5 months (range: 7 - 24 months), and were alive at the reporting time. Of the five patients who died, three survived for a mean of 26 months (range: 21 - 36 months).
The patients with three-component tumors presented at a mean age of 68 years (range: 52 - 81 years) and the male/female ratio was 1:3. The patients presented with epigastric (3/8), RUQ (2/8) and abdominal (1/8) pain; two patients were asymptomatic. Two of eight patients presented with anorexia or weight loss. Gallstones were documented in 5/8 patients. The mean size of tumor was 5.2 cm (range: 3.6 - 8.2 cm), and was located in the fundus in 5/8, and in the gallbladder neck in 1/8 patients. The tumor was composed of large cell NEC in 4/8, small cell NEC in 1/8 and unspecified NEC in 2/8 patients. Sarcomatoid differentiation was observed in two patients. The proportion of tumor components was reported in only three patients (including the patient presented here). All three patients had ≥ 50% of the tumor composed of SCC, and neuroendocrine component comprised 10-30% of the tumor. One patient presented with metastasis only to regional lymph nodes, 2/8 presented with direct liver invasion, 3/8 presented with liver metastasis and two presented with distant metastasis to the umbilicus or bone. Three of the eight patients received chemotherapy; one was treated with oxaliplatin and gemcitabine and another with cisplatin, gemcitabine and epirubicin. Our patient was given leucovorin, oxaliplatin and 5-FU. The patients with tumors localized in the gallbladder and those with only regional lymph node metastasis were disease-free for 8 and 48 months, respectively. The four patients who died between 5 and 32 months (mean: 14 months) all had metastasis.
The origin of gallbladder neuroendocrine neoplasms is enigmatic. Neuroendocrine tumors of the tubular gut most often occur in the rectum, appendix and ileum where they arise from hormone-producing cells known as amine precursor uptake and decarboxylation (APUD) cells. However, normal gallbladder mucosa lacks APUD cells. At least two different hypotheses have been proposed to explain the origin of neuroendocrine tumors of the gallbladder: these arise from the epithelial metaplasia of the gallbladder which includes goblet cells and enterochromaffin and from pluripotent stem cells. This is based on demonstration of shared immunoreactivity patterns between different tumor components and common characteristics (featuring both neuroendocrine and glandular differentiation) observed in electron micrographs [5, .
Gallbladder small cell NECs have molecular abnormalities that overlap with those observed in gallbladder adenocarcinomas. Molecular studies of 12 gallbladder small cell NECs revealed loss of heterozygosity (LOH) at 16p13 (TP53 locus) in 77% of the cases, a finding also observed in 92% of gallbladder adenocarcinomas. Similarly, LOH at 9p21 (INK4a locus) and 18q21 (DCC and DPC416 loci) found in 44% and 43% of small cell NEC cases were similar to those reported in gallbladder adenocarcinomas (50% and 31%, respectively). KRAS mutation, found in 17% of small cell NEC cases, is considered a low frequency (0-17%) in gallbladder adenocarcinomas. However, studies from Japan reported a higher frequency of KRAS mutation in gallbladder adenocarcinomas [] (
.
Molecular studies showed that CDKN2A/B and APC mutations were present in 27% and 3% of pancreatic NECs, respectively, a pattern similar to that of pancreatic adenocarcinomas where the mutations were present in 28.3% and 2.5%, respectively. Similarly, CDKN2A/B and APC mutations were present in 6% and 47% of colon NECs, in comparison to 9.8% and 49.3% of colon adenocarcinomas, respectively () .


A 49-year-old female with no significant medical history presented with one-month history of progressive peripheral vision loss and headache. She had also experienced polydipsia with polyuria and further history revealed that she was amenorrhoeic for one year. Otherwise, she has no respiratory or constitutional symptoms. Physical examination was unremarkable except that visual field examination confirmed bitemporal hemianopia (). A subsequent cranial magnetic resonance imaging (MRI) scan displayed a lobulated heterogeneous enhancing mass approximately 1.7 x 1.9 x 2.0 cm arising from the sella turcica with suprasellar extension and compression of the optic chiasma (). Initial laboratory tests showed normal blood count, Na: 144 mmol/L (reference value [RV]:136-145), K: 4.1 mmol/L (RV: 3.5-4.4), and creatinine: 52 umol/L (RV: 44-80). Serum osmolality: 365 mOsm/kg (RV: 275-295) and urine osmolality: 66 mOsm/kg (RV: 300-900) taken during the polyuric phase were consistent with diabetes insipidus. Hormonal evaluation demonstrated insufficiencies of the corticotropic, thyroid and gonadotropic axis. (). She was started on hormonal replacement therapy (T. Hydrocortisone 10 mg BD, L-Thyroxine 25 mcg OM and T. Desmopressin 0.1 mg BD).
The patient underwent endoscopic transsphenoidal pituitary surgery with resection of the mass. The postoperative recovery was uneventful and was discharged well with hormonal replacement therapy. She was seen in clinic one week postoperatively with the complaint of left shoulder pain. Left shoulder x-ray showed pathological fracture of the left proximal humerus () and chest radiography () showed suspicious left lung nodule. A chest radiography was not done pre-operatively as there were no prior clinical indications. Pituitary histopathological analysis was later reported as metastatic adenocarcinoma. CT of the thorax, abdomen and pelvis revealed a mass (3.3 x 4.9 x 3.6 cm) at the posterior basal segment of left lower lobe () with multiple lung nodules of varying size noted bilaterally, enlarged mediastinal and hilar lymph nodes, and lytic lesion at proximal humerus and L5 vertebral body.
Subsequently, patient underwent CT guided biopsy of the left lung mass. The histopathological analysis was consistent with pulmonary adenocarcinoma and the immunohistochemistry results were positive for cytokeratin 7 (CK7) and thyroid transcription factor 1 (TTF1) and negative for CK20 and thyroglobulin. Patient underwent stereotactic radiation therapy to the pituitary mass and was started on oral chemotherapy gefitinib.


A 14-year-old boy was admitted in the hospital with high fever, pain in throat and cough associated with muscle cramps and generalized body pain for one week. He was a known case of transfusion-dependent β-thalassemia (detected at 9 months old), was regularly receiving packed red blood cell (RBC) transfusion (starting from 18 months old) and requiring, on average, 4 units per month. He was maintained on Deferiprone (500 mg thrice daily) for a long time and was also put on deferoxamine mesylate since his serum ferritin went above 10000ng/dl one year prior to admission.
He was also treated conservatively for fever and muscle cramps about a year prior to admission, but no details were available. He had recurrent convulsive seizure at that time. Electroencephalography (EEG) showed nonspecific changes and Magnetic resonance imaging (MRI) brain was normal. Anticonvulsant therapy (Phenobarbitone 60 mg daily) was given since then, with a presumptive diagnosis of epilepsy along with other regular treatments for thalassemia.
Following this admission in the hospital for high fever, he experienced several episodes of severe muscle cramps and generalized body pain. He was conscious, febrile, anaemic and sick. The examination of the patient’s pharynx revealed mild erythema with pharyngeal exudates. He was flushed, had hepatosplenomegaly, with no local muscle tenderness in limbs and positive Trousseau’s sign. He had no other focal neurological deficit.
Laboratory evaluation showed hemoglobin: 10.5 gm/dl (13-16), leucocyte: 12,400/cumm (3500-9000), erythrocyte sedimentation rate: 44 mm (0-20), potassium: 2.45 meq/l (3.5-5.0), urea: 16 mg/dl (3.5-7.0) and creatinine: 0.83 mg/dl (0.7-1.3), serum ferritin: 8976 ng/dl (7-140), serum calcium: 3.8 mg/dl (9-10.5), phosphate: 11.53 mg/dl (2.7-4.5), alkaline phosphates: 86 U/L (53-141), serum albumin: 3.9 mg/dl, albumin corrected serum calcium: 3.98 mg/dl and repeat serum calcium: 4.1 mg/dl (9-10.5). His liver function test was abnormal with raised indirect bilirubin of 2.41 mg/dl (0.1-0.9) but normal direct bilirubin of 0.4 mg/dl (0-0.4) and normal aspartate transaminase 17 IU/L(8-40). His fasting plasma glucose and thyroid function test was normal.
Throat swab was obtained and was cultured. Grampositive cocci suggestive of Streptococcus pyogenes grew in chains. No blood culture was done. His iPTH was very low: <2.5 (14-70 pg/ml) and serum vitamin D level was 34.62 ng/ml (30-100). The patient was diagnosed as a case of primary hypoparathyroidism and was evaluated for serum magnesium (Mg) which was also very low:0.53 mg/dl (1.5-2.5).
He was treated with an antibiotic from day 1 for the fever and congested throat. Magnesium replacement (20 mmol/ day for 6 days in intravenous route) along with calcium replacement (Ca-gluconate in intravenous route) was started on the second day of admission and daily monitoring of calcium, phosphate and magnesium was done. Calcium level and Magnesium level gradually improved from 2nd day to 6th day while serum phosphate level gradually declined (). Hypomagnesaemia contributes to hypokalemia and he was closely monitored in the Intensive Therapy Unit. However, his serum potassium gradually improved from 2.45 meq/l (on admission) to normal levels (4.30 meq/l) on 6th day without potassium supplementation.
His episodes of severe muscle cramps and pain all over the body gradually improved, as well as the fever and congested throat. Intravenous calcium and magnesium replacement was stopped after 6th day and oral calcium (1000 mg daily), calcitriol (0.5 ug) and oral magnesium (400 mg daily) were started. On the 8th day, two days after oral supplementation was started, serum calcium was 6.7 mg/dl, magnesium 1.14 mg/dl and phosphate 4.9mg/ dl. The iPTH was repeated and was at a low normal value of 16.5 (14 – 70 pg/ml). The dose of oral calcium (1500 mg daily) and calcitriol (1.5 ug) was then increased. Biochemical parameters improved further (Serum calcium 8.7 mg/dl, magnesium 1.24mg/dl and phosphate 4.4mg/dl) on the 12th day (). He had no further seizure and was discharged from the hospital. Repeat serum ferritin before his discharge came down to 7795 ng/dl.
On follow up, he was maintained on blood transfusions, deferiprone, deferoxamine mesylate, oral calcium and calcitriol without any history of muscle cramps or convulsion. The anticonvulsant (Phenobarbitone) was gradually withdrawn over the next six months. He did not have any further episode of convulsion over 3 years of follow up.


A 60-year-old Japanese male was referred to the Department of Gastrointestinal Surgery after the incidental detection of a retroperitoneal tumor without symptoms. The patient had a previous history of HCV infection; however, no abnormalities existed on hematological examination and an anti-HCV antibody test was negative. Contrast-enhanced abdominal CT revealed around 25-mm-sized retroperitoneal tumor with heterogeneous enhancement on the left of the aorta (Fig. ). MRI demonstrated that the tumor exhibited iso-signal intensity on T1-weighted images, moderate-to-high intensity on T2-weighted images, and high intensity on diffusion-weighted images (Fig. ). After informed consent, the tumor was surgically removed. In addition, pathological findings revealed a fused glandular neoplasm composed of enlarged cells with atypical nuclei (Fig. ). An immunohistochemical profile included positive results for AR (Fig. ), PSA (Fig. ), and NKX3.1 (Fig. ), and negative results for cytokeratin 7, cytokeratin 20, thyroid transcription factor 1, CDX-2, chromogranin A, CD3, CD20, estrogen receptor, progesterone receptor, hepatocyte-specific antigen, and prostate-specific membrane antigen (Fig. ). Histopathological findings revealed a poorly differentiated adenocarcinoma in which the MIB-1 index, determined by the number of Ki67-positive cancer cells, was 28.5% (Fig. ). These results suggested the primary site of the tumor was the prostate, and, therefore, the patient was referred to our department. The patient’s serum PSA level was 3.67 ng/mL, and a digital rectal examination was unremarkable. Other serum tumor markers, including β-chorionic gonadotropin, cancer antigen 19-9, and carcinoembryonic antigen, were within normal range. 18F-fluoro-deoxyglucose positron emission tomography did not show abnormal uptake in the prostate or other organs (Fig. ). Three-Tesla MRI revealed a normal prostate without a cancerous lesion (Fig. ). An ultrasound-guided 12-core transperineal systematic prostate biopsy revealed no malignant cells. Therefore, the patient chose no further treatment. However, 3 months later, CT revealed multiple lymph node swellings, including in left supraclavicular and para-aortic sites (Fig. ); the PSA doubling time was 6.9 months. On the basis of a final diagnosis of CUP, the patient underwent CAB therapy as ADT, including a luteinizing hormone-releasing hormone antagonist and 80 mg of bicalutamide after obtaining the approval of the institutional cancer board. His serum PSA quickly reached a nadir level without any adverse events; 3 months after the initiation of ADT, all lymph node swellings had disappeared on CT (Fig. ). The patient successfully showed progression-free survival for 4 years with continuous primary CAB as an outpatient.
This study was approved by the Nagoya City University Graduate School of Medical Sciences Institutional Review Board (#60200039). Written informed consent was obtained from the patient for publication of this article and accompanying images.


A previously healthy 45-year-old man presented to our emergency department complaining of typical cardiac chest pain, which started 1 hour before presentation. The patient was a smoker and had no family history of cardiovascular disease. His blood pressure was 110/70 mm Hg. Auscultation of the heart revealed normal heart sounds with no murmurs. The patient’s initial ECG () showed normal sinus rhythm with ST-segment elevation in leads aVR, V1, and V3R through V5R with diffuse prominent ST-segment depression in other extremity leads, identifying left main or severe multivessel disease. He underwent coronary angiography that revealed a proximal total occlusion of the RCA. No significant lesions were found in the left anterior descending and the circumflex arteries. A drug-eluting stent was deployed in the RCA. The final angiographic outcome was excellent (). Subsequently, the patient showed symptomatic improvement, the ST changes resolved, and he was discharged 3 days later in a stable condition.


A 43-year-old male with past medical history of end stage renal disease (ESRD), cirrhosis and chronic obstructive pulmonary disease, presented for a right lung decortication for a hemothorax. Preoperative airway examination revealed an edentulous Mallampati one, and no notable risk factors for aspiration. After an uneventful induction, the patient was intubated with a 37 mm left sided double lumen tube (DLT) for lung isolation using a Miller#2 blade. Bilateral air entry and ETCO2 were confirmed. Fiberoptic bronchoscopy performed through the tracheal lumen of DLT. Upon the bronchoscope exiting the tracheal lumen we visualized a tablet sticking to the junction of carina and right main bronchus with no major obstruction []. The surgeon immediately notified, but decided to proceed with surgery prior to retrieving the tablet due to the need to switch out the DLT for a single lumen endotracheal tube. At the end of procedure, the DLT changed to an 8.0 mm single lumen endotracheal tube and the tablet was removed in pieces using a flexible fiberoptic bronchoscopy and lavage with difficulty. The patient was extubated uneventfully in the OR and transferred to the ICU. The postoperative period was uneventful. X-ray chest of the patient on the day of surgery and CT chest two days prior to surgery did not show any radio opacity in tracheobronchial tree []. From the patient's medication history, we suspect the pictured tablet was a Sevelamer 800 mg given the evening before the day of surgery [].


A 45-year-old female, one of three backseat passengers of a commercial tricycle and who was seated on the left side with both feet inside the vehicle but the left lower limb abducted such that the left knee and adjoining regions protruded outside the vehicle while on the highway.
A fast-moving saloon car moving in the same direction drove past the tricycle and hit the protruding knee without having any contact with the tricycle. She sustained open injuries to the left lower limb from which she bled profusely at the site of the accident, and she had dizzy spells.
She was referred to us 5 hours after the injury having had some resuscitation at a nearby health facility. Clinical examination showed a conscious and anxious woman, who was pale, tachycardic (pulse rate of 120/min), and tachypneic (respiratory rate of 30/min) with blood pressure of 110/70 mmHg. She had extensive crush and avulsion injuries to the soft tissues of the distal left thigh, popliteal fossa, and the proximal half of the left leg. There was a complete disruption of the neurovascular structures of the popliteal fossa, the distal left thigh was deformed, and there was an exposed fracture of the proximal left tibia []. The limb was cold and insensate distal to the site of injury.
She was further resuscitated with intravenous fluids, her packed cell volume was 24%, and she had three units of whole blood transfused. Supplemental oxygen was administered, and the wound was thoroughly irrigated with normal saline and dressed.
X-rays confirmed an oblique fracture of the distal femur in the supracondylar region, a segmental fracture of the proximal fibula, and the proximal tibial shaft fracture. It also showed the disruption of all layers of the soft tissues in the affected region [Figures and ].
Mangled extremity severity score was 7 on arrival. A joint review by both the orthopedic and the cardiovascular surgery teams adjudged the limb unsalvageable, and she was counseled for ablative surgery. Intraoperatively, the above findings were confirmed, the retracted and thrombosed severed ends of the popliteal vessels were identified, and the tissues of the limb below the level of injury were no longer viable. She thereafter had a left above-knee amputation done and subsequently had an uneventful immediate postoperative and rehabilitative period.


During a routine chest X-ray examination, a 50-year-old man was diagnosed with an abnormal shadow in the right chest. As there were no signs to suggest the mass was malignant, the patient decided to forego further examination or treatment.
Ten years after the initial discovery, a routine chest X-ray revealed an increase in the size of the previously detected shadow, and the patient was advised a biopsy and tumor removal. However, the patient refused further examination or treatment in the absence of any symptoms. Thirty years after the initial discovery, the patient was hospitalized with symptoms of severe hypoglycemia. Prior to the acute episode necessitating hospitalization, the patient had no history of hypoglycemic symptoms, such as sweating, palpitations, and loss of consciousness. Moreover, there was no history of an increase in weight for the preceding 6 mo. As the patient’s hypoglycemia was resistant to treatment by frequent oral glucose supplementation, he was hospitalized for further management.
The patient had no medical records or family history of hypoglycemia.
The patient was on treatment with azelnidipine for hypertension and rosuvastatin for hyperlipidemia.
Clinical examination revealed no signs, except attenuation of respiratory sounds over the right chest.
Laboratory test results (Table ) after hospitalization showed a slight increase in C-reactive protein (CRP) levels to 2.11 mg/dL. The anti-insulin antibody test result was negative, and fasting blood glucose was 48 mg/dL, accompanied by a low immunoreactive insulin (IRI) level of < 5.0 µU/mL. Interestingly, there was no change in the levels of insulin-counterregulatory hormones, such as cortisol, growth hormone (GH), and norepinephrine (Table ).
Chest X-ray and computed tomography (CT) scanning showed a giant solid tumor (11 cm × 14 cm × 15 cm) in the right lower chest region (Figure and ). A fluorine-18 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography showed uneven accumulation of the maximum standardized uptake value (SUVmax 3.1) indicating possible characteristics of a malignancy (Figure ). Interestingly, the mass showed a propensity for accumulation by octreotide scintigraphy, which was characteristic of a neuroendocrine tumor (Figure ).
From the biochemical and histological findings, we suspected an NICTH. To confirm this diagnosis, we undertook a core biopsy of the tumor. Immunoblots of serum IGF-II and tumoral tissue IGF-II from tumor biopsies were conducted[], and a high-molecular-weight form of IGF-II was identified in both types of samples on Western blotting (Figure ). Furthermore, immunohistochemical staining for IGF-II in tumoral tissue showed numerous immunopositive tumor cells (Figure ).


A 51-year-old woman presented with mild left shoulder pain.
Shoulder pain started 7 d previously when the patient was walking. No sweating, fatigue, or nausea was reported by the patient. She visited the local hospital and underwent physical examination and a left shoulder X-ray, but with no significant findings. The treating physician suspected possible scapulohumeral periarthritis and discharged the patient with oral analgesics. After taking NSAIDs for three days, her shoulder pain did not improve, and the patient came to our ED for further investigation.
She was diagnosed with AD (Stanford type B) for more than 10 years. However, she did not receive any surgical intervention and only had antihypertensive medications.
The patient had no remarkable personal and family history.
At the time of admission, physical examination revealed an elevated blood pressure of 139/93 mmHg, heart rate of 78 bpm, and oxygen saturation of 98% in room air. No movement limitation of the left shoulder was observed.
Emergent contrast-enhanced computed tomography angiography confirmed the diagnosis of a new type A AD with a sizable false lumen (Figure ).


A 33-year-old man presented with a history of progressive fatigue and worsening upper spinal pain (). Previous chest radiography showed enlargement of the right hilar lymph nodes, without parenchymal lesions in either lung (). Thoracic computed tomography (CT) revealed clear enlargement of the right hilar lymph nodes in the paratracheal and prevascular regions (), which had not changed compared with imaging results from 3 years prior. There was no history of trauma and no significant medical history. Spinal magnetic resonance imaging and HLA-B27 haplotype testing were also performed to exclude spinal diseases. Considering the patient’s previous examination results, and unchanged symptoms and imaging results for more than 3 years, the presumed origin for his back pain was musculoskeletal.
On the latest visit, the patient reported worsening of his pain, with a choking sensation in his chest, fatigue and night sweats. Physical examination revealed a body temperature of 37.2°C. The patient had no cough, expectoration, joint pain, haemoptysis or dyspnoea. Repeat thoracic CT revealed clear changes in the pulmonary interstitial tissue along with consolidation in the right upper pulmonary lobe, pleural parenchymal thickening and bronchial erosion and compression near the enlarged lymph nodes (). These changes suggested a likely diagnosis of tuberculosis; therefore, he was admitted to the tuberculosis hospital for further diagnosis and treatment. The tuberculin skin test result was strongly positive (50 mm with blister formation). Laboratory examinations revealed a high erythrocyte sedimentation rate (ESR) of 35 mL/hour (reference range < 15 mL/hour) and a high ratio of mononuclear leucocytes. A diagnosis of pulmonary tuberculosis, likely secondary to mediastinal tuberculosis, was made. Fine-needle aspiration was suggested, but the patient refused. A subsequent sputum test was positive for Tuberculosis bacilli, which were sensitive to anti-tuberculous drugs (rifampin, isoniazid, ethambutol, pyrazinamide and levofloxacin). Treatment with daily adjusted doses (weight: 70 kg) of rifampin (0.6 g), isoniazid (0.4 g), ethambutol (1 g) and pyrazinamide (1.5 g), were initiated. All investigations, including complete blood counts and liver and renal function tests, were within acceptable limits during treatment, and he was followed-up routinely throughout the treatment period. His vaccination history did not reveal a scar that indicated Bacillus Calmette–Guérin (BCG) vaccination. His medical history, as well as that of his family, was unremarkable regarding exposure to tuberculosis.
Despite treatment, his back pain worsened significantly and was accompanied by painful dysphagia from the first month of the anti-tuberculous treatment. Thoracic CT revealed newly increased inflammation owing to MTL (). The continuation phase of his anti-tubercular treatment was maintained, and he was followed-up closely. Three months later, he visited the hospital and reported symptom improvement. Significant shrinkage and improvement with calcification were observed in the hilar and mediastinal nodes and less lung and bronchial compression were seen after 12 months of anti-tuberculous treatment (). Because this case involved pleura, hilar and mediastinal tuberculosis, the patient was advised to maintain the continuation phase treatment for 18 months, which consisted of three drugs (isoniazid, rifampicin and ethambutol) with frequent follow-ups. These lesions heal with fibrosis and calcification. His back pain gradually resolved and did not recur, and he is currently in follow-up and is at risk of relapse.


A 32-year-old female, gestational age 22+5 wk, presented to the department of obstetrics of our hospital complaining of abdominal distension, chest tightness and limb weakness lasting approximately 4 wk. Ovarian tumors were found 14 d ago.
Fifty-five days prior (gestational age: 14+6 wk), her ultrasound showed no mass in the bilateral adnexal area. According to the patient, her abdominal distension, chest tightness, and limb weakness began approximately 4 wk prior (gestational age: approximately 19 wk), but she did not seek treatment. Fourteen days ago, she was diagnosed with bilateral ovarian tumors in another hospital by ultrasound showing a hypoechoic mass measuring 9.2 cm × 6.7 cm on the right side of the uterus, a hypoechoic mass measuring 9.2 cm × 6.9 cm on the left side of the uterus, an anechoic mass measuring 4.3 cm × 3.6 cm beside the uterus and pelvic effusion.
The patient noted a history of gastritis for more than 10 years.
Her parents had a history of hypertension. She had no family history of malignancies.
Her face showed signs of anemia. Her chest percussion was voiced, and her abdomen was swollen. A trimanual gynecologic examination after induced labor revealed a uterus with poor mobility, irregular masses in the bilateral adnexal area with poor mobility, a rectal fossa filled with lesions and a narrow space between the intestines.
Upon admission, her laboratory results were as follows: hemoglobin 66 g/L, hematocrit 20.4%, reticulocyte 3.28%, serum albumin 35.1 g/L, free triiodothyonine 2.34 pmol/L, and free thyroxine 16.35 pmol/L. Tumor marker levels were as follows: CA125 578.50 U/mL, alpha-fetoprotein 157.84 ng/mL, carcinoembryonic antigen 0.53 ng/mL, CA199 16.13 U/mL, Cyfra21-1 2.60 ng/mL, Fer 749.58 ng/mL, β 2-microglobulin 5.56 μg/mL, neuron-specific enolase 15.84 ng/mL, CA50 7.19 U/mL, CA153 25.70 U/mL and serum lactic dehydrogenase (LDH) 1160 U/L.
At admission, ultrasound indicated a hypoechoic mass measuring 10.7 cm × 7.8 cm in the right adnexal area and a hypoechoic mass measuring 11.2 cm × 8.2 in the left adnexa. Then, pelvic magnetic resonance imaging (MRI) showed a soft tissue mass shadow in the pelvic cavity measuring approximately 12.7 cm in the largest diameter and lesions involving the posterior wall of the bladder, adjacent bowel, cervix, upper part of the vagina and bilateral iliac vessels. The patient was diagnosed with a bilateral adnexal malignant tumor, and the pelvic mass was not excluded as metastasis (Figure -). MRI also revealed pelvic effusion, soft tissue swelling in the pelvic wall and buttock, changes in the pelvic bone and bilateral ureteral dilatation.
Ultrasonography and computed tomography (CT) showed massive peritoneal and bilateral pleural effusion. Therefore, we performed ultrasound-guided puncture catheter drainage in the abdominal cavity and right thoracic cavity. Whole-abdomen CT showed bilateral pleural effusion, abdominal and pelvic effusion and malignancies of the bilateral adnexal origin that did not involve the rectum and bladder (Figure and ). Whole-abdomen CT also revealed an irregularly shaped uterus and cervix that were not excluded as metastases, multiple soft tissue masses in the abdomen believed to be metastases, a nodular shadow in the left lateral lobe of the liver that was not excluded as metastasis, tumor involvement in the bilateral middle and lower ureters, secondary left kidney atrophy, bilateral hydronephrosis, bilateral upper ureteral dilatation and bilateral inguinal lymph nodes. After receiving the pathological results, positron emission tomography-computed tomography (PET-CT) was performed and revealed multiple enlarged lymph nodes throughout the body with increased metabolism (indicative of lymphoma), some lesions that were unclearly demarcated from the uterus and adnexa, thickening of the bilateral pleural wall, pleura, pericardium, peritoneum, omentum and mesentery with increased metabolism (indicative of lymphoma infiltration), lymphoma in the right breast and increased systemic skeletal metabolism (indicative of lymphoma infiltration).
The exfoliative cytology of hydrothorax and hydroperitoneum showed many lymphocytes without cancer cells. The pathological results supported high-grade B-cell lymphoma, and the immunohistochemical staining results were as follows: LCA (+), CD20 (+), CD3 (-), CD5 (-), Cyclin D1 (-), Ki67 (positive rate 90%), CK (AE1/AE3) (-), BCL-6 (+), TdT (-), MPO (-), CgA (-), Syn (-), CD56 (-), PAX-5 (+), CD34 (-), CD10 (+), BCL-2 (+), MUM1 (-), MYC (+), CD21 (-) and CD99 (weakly +). The pathological consultation at the superior hospital resulted in a diagnosis of non-Hodgkin high-grade B-cell lymphoma with rearrangements of the MYC gene and BCL2 gene (DHL). Immunohistochemistry revealed MUM-1+, CD10+, CD38+ and LMO 2- and in situ hybridization revealed EBER-.


A 35-year-old male came to the emergency with alleged history of roadside accident. The patient was hit from behind from a speeding vehicle and with the impact patient was thrown onto the road with both outstretched hands planted firmly on the ground (to break the impact of fall) with varus stress on both elbows (). This usually produces ulna fracture with tension failure at radial side first and lateral radial head dislocation. There were no external wounds or any distal neurovascular deficit in both upper limbs. There was no history of loss of consciousness or any history of seizures or vomiting and the patient was brought to the emergency department. Here, the patient underwent radiographic imaging of both forearms with elbow with wrist anteroposterior and lateral views. Bilateral above elbow slabs given. X-rays showed proximal 1/3rd ulnar shafts with lateral radial head dislocation ( and ), which accounts for Bado classification typeIII Monteggia fracture bilaterally, which almost exclusively occurs in children, but a rare occurrence in adults as in this case report []. Workup for surgery was done and was taken to the OR, where the patient was placed in a supine position, skin preparation and draping was performed for both upper limbs. A posterior skin incision was first performed on the right forearm. An anatomical reduction was achieved, and open reduction and internal fixation of the bilateral ulna were done with posterior anatomical plates and closed repositioning of radial head was done bilaterally. Fluoroscopy was used to confirm appropriate articular reduction, position of the devices, and ulnohumeral joint reduction. The elbow appeared stable through full range of motion and wound closed in layers and suction drain out bilaterally. Postoperatively, bilateral above-elbow pop slabs were given. Post-operative X-rays were performed (, , , ). Drains were removed after 48 h; at that time, the patient started passive-assisted exercises and active motion and pop slabs reapplied. Alternate day dressings were done, and skin sutures removed on 21st post-operative day along with the slabs. The patient was advised physiotherapy. X-rays were performed at 1 month of follow-up () and then again at 5 months of follow-up () along with clinical pictures after 5 months of follow-up (, , , , , ).


An 86-year-old female was referred for evaluation of a painful native left hip. Diagnosed with advanced osteoarthritis [], she consented for a THR. Preoperative digital templating was performed, and appropriate implants were selected. At the discretion of the operating specialist, the case performed using the Intellijoint HIP® 3D min-optical navigation tool (Intellijoint Surgical Inc., ON, Canada).
The operation was performed without complication, employing a routine posterior approach, an uncemented implant constructs, the Intellijoint® navigation system, and otherwise standard surgical technique. Facilitating navigation utilization, two 4.0 mm pins were placed into the ipsilateral iliac crest. The patient mobilized independently on day one and recovered unremarkably. She was seen postoperatively at 2 and 8 weeks [] with a stable hip, no clinically-appreciable leg length discrepancy, and was “extremely happy” with her result.
Unfortunately, 4 months after surgery, the patient fell heavily onto her operative side having been knocked over by a large dog (45 kg). She was transported to the local emergency department (remote to the site of her index hip surgery), where X-rays demonstrated a Vancouver B2-type periprosthetic fracture. A 3D computed tomography (CT) scan[] was performed for the assessment of fracture propagation and host bone stock.
The metal-artifact-reduced (MAR) CT scan was reported by an experienced senior radiologist describing the oblique peri-prosthetic fracture with a displaced greater trochanteric fragment. However, the report flagged a “sclerotic lesion showing prominent periosteal reaction” associated with the “left iliac bone” [ and ]. This concerning finding was communicated directly to the referring emergency physician with a presumptive incidental diagnosis of an “aggressive, early-stage, pelvic chondrosarcoma.” Metastasis was raised as a differential, reinforced by a known strong family history of malignancy. The patient was referred to the regional orthopedic oncologic service and a tertiary transfer arranged. A MAR magnetic resonance imaging (MAR MRI) and single-positron emission CT (SPECT) scans were ordered for staging.
At this point, the index hip surgeon was contacted (<24 h post-fall). A review of the preoperative imaging did not show evidence of a comparable lesion and the rapidity of evolution was questioned. Correlation of the radiographic lesion location with a physical assessment of the patient confirmed the subjacent relationship to the previous pelvic pin sites. Discussed directly with the reporting radiologist, the patient's full relevant imaging catalog was reviewed via picture archiving and communication system (PACS). An amendment to the gazetted CT report was issued reflecting “periosteal and cortical features in keeping with the location and insertion of recent surgical navigation pins to the left iliac crest.” The ordered MRI and SPECT scans were cancelled. Repeat imaging at 4 months post-revision surgery (i.e., 7.5 months post-index surgery) showed complete resolution of the sclerotic/periosteal features.


A 79-year-old male patient who presented progressive dyspnoea and cardiac decompensation was presented in the heart team meeting. The patient had been known with an extensive medical history including diabetes, atrial fibrillation (AF), non-Hodgkin lymphoma, and hostile chest. He had undergone a percutaneous coronary intervention to the left anterior descending artery for non-ST-elevation myocardial infarction 3 years ago and a TAVI due to severe aortic valve stenosis 1.5 years ago.
Seven months after the TAVI, the patient was hospitalized in a peripheral hospital due to persistent high fever including night sweating and chills. The blood bacterial test showed instant Gram-positive and subsequent blood culture-confirmed positive Streptococcus mitis infection. Blood culture of other suspicious Gram+ bacteria and urine culture yielded negative results. The TOE revealed a suspicious mobile structure in the left ventricular outflow tract and 6 days later the TOE was repeated and demonstrated tissue thickening and abscess formation around the aortic bioprosthesis with a large vegetation extending towards the anterior mitral valve leaflet. The multidisciplinary endocarditis team acknowledged the indication for surgery because of the explicit TOE findings; however, the patient was deemed inoperable due to the hostile chest (sternum destruction from non-Hodgkin lymphoma). Therefore, the patient received prolonged antimicrobial therapy (∼6 months). At 1-year follow-up visit of TAVI, the patient seemed fully recovered and the transthoracic echocardiography (TTE) showed no more signs of vegetation or other destructive findings.
At the subsequent follow-up visit 8 months later, the patient presented again with progressive dyspnoea and New York Heart Association (NYHA) Class 4, without fever, pain, or other complaints. Besides a Grade 2 diastolic cardiac murmur, the physical examination yielded no other significant findings. The blood culture yielded negative results and C-reactive protein (CRP) level was not elevated. The TTE revealed significant MR with an eccentric jet due to posterior mitral leaflet tethering () and enlarged mitral annulus (diameter 41 mm in the apical four-chamber view). The MR flow convergence radius was 7 mm with an effective regurgitant orifice area (EROA) of 22 mm2. The mitral inflow E-velocity was 1.3 m/s. The MR was deemed as severe functional MR. The left ventricular ejection fraction was 55% and the diastolic function could not be ascertained due to AF. The aortic bioprosthesis appeared unremarkable with mild paravalvular leakage (PVL) (). There was also moderate tricuspid regurgitation with a systolic pulmonary artery pressure of 49 mmHg. The subsequent TOE confirmed the MR aetiology and severity (with obvious pulmonary vein systolic flow reversal). To assess the eligibility of MitraClip implantation, the following parameters were measured: posterior leaflet length (P2) 17 mm, coaptation length 3 mm, and coaptation depth 4 mm. There was no significant calcification on the annulus, leaflets, or subvalvular chordae.
Based on the symptoms, laboratory and echocardiographic results, the possibility of endocarditis relapse was ruled out. According to the latest recommendation of the decision pathway on management of MR, this patient was deemed inoperable due to multiple comorbidities and eligible for a MitraClip procedure by the multi-disciplinary heart team based on:
TTE findings: Severe MR based on TTE and TOE using the multi-parametric approach including EROA, dominant mitral inflow E wave, and pulmonary vein flow systolic reversal MR aetiology secondary to annular dilatation (presumably caused by permanent AF) and posterior leaflet tethering (presumably caused by the prior myocardial infarction) Normal mitral valve area and transmitral pressure gradient
TOE findings: MR aetiology and jet location (A2-P2) Adequate posterior leaflet length, coaptation length and small coaptation depth no significant calcification on leaflets grasping zone
Intra-procedural TOE (2 weeks after the pre-procedural TOE) confirmed mixed aetiology of degenerative and functional MR including posterior mitral leaflet tethering and leaflet malcoaption () and anterior leaflet billowing (Videos and ). Additionally, a significant continuous shunt through a fistula between the aortic left coronary cusp region and left atrium was noticed (, , Video S), which was deemed a sequela of the prior endocarditis episode. The treatment strategy was therefore modified to first occlude the fistula with an Amplatzer Vascular Plug II (AVP II, St. Jude Medical, Abbott). A 6-Fr Amplatz left the diagnostic catheter in combination with a 0.035″ Kimal straight wire was easily navigated through the fistula from the sinus of Valsalva (). This assembly was exchanged for a 7.5-Fr sheathLess JR4 Guiding Catheter (Asahi Intecc Co Ltd) () over a 0.035″ Safari small Guidewire (Boston Scientific) (). A 12 mm AVP II was released in the fistula (, , Video S) leaving an insignificant residual shunt (). The severe mixed (leaflet tethering, annular dilation, and A2 billowing) MR persisted after the plug deployment. After the transseptal puncture one MitraClip XTR (Abbott Vascular) was implanted on the central-lateral position (, , Video S) reducing the MR from severe to mild () with a transmitral pressure gradient of 2 mmHg. After the procedure, the patient’s general clinical condition improved without signs of haemolysis. The pre-discharge TTE confirmed all devices in situ with trace residual shunt, mild residual MR and mild PVL (). The patient was discharged 3 days after the procedure. During the most recent follow-up (6 months after the procedure) the patient presented a reasonable state: NYHA Class 2, no fever or syncope, stable vital signs without significant heart murmur. There was no limb oedema but the signs of gout. Laboratory results yielded increased creatinine and CRP levels. The deterioration of the renal function had been identified before the procedure and elevated CRP level was suspected due to the gout. The TTE showed sustained results: mild residual MR, mild residual AAF shunt and mild-moderate PVL of the aortic prosthesis.


A clinical case of a 55-year-old patient with prostate carcinoma who was treated with parenteral BPs received an X-ray diagnosis of non-exposed BRONJ with normal intraoral findings in the right upper jawbone from area 17 to retromolar area 19. While 2D-OPG of area 18/19 showed no suspicious findings, the CBCT/DVT image demonstrated ossification irregularities and partial cavities that resembled AIOJ/BMD/FDOJ. The development and progression of BRONJ could not be reliably determined by reference to these images and it was not possible to make a differential diagnosis. In contrast, TAU-n images clearly indicated osteolysis (see , below). The postoperative light microscopy findings from area 18/19 showed marrow with adipose tissue, significant fibrillar and myxoid degeneration of adipocytes, individual lymphocytes, and mast cells; however, no florid inflammation was observed. These are the typical histological features of AIOJ/BMD/FDOJ. It is worth noting, however, that there was a large bone sequestrum with empty OC cavities, highly irregular trabecular surfaces, and empty marrow spaces, with Actinomyces colonization ().
Several reviews have indicated that light microscopy examinations were able to detect that 68.8% of BRONJ cases featured Actinomyces colonization. Anaerobic Actinomyces has long been associated with necrotic bone findings in BRONJ lesions. Actinomyces colonization is thus a top priority as a possible pathological trigger with respect to BRONJ. Since we have not identified bacterial colonization in areas of AIOJ/BMD/FDOJ in our own studies, an accompanying secondary Actinomyces colonization seems to be an additional prerequisite for the development of BRONJ from an area of AIOJ/BMD/FDOJ in response to BP administration.


A 55-year-old postmenopausal woman had intermittent chest pain for 3 years.
Three years ago (on January 20, 2016), the patient experienced chest pain following an emotionally stressful event (quarrel with her husband) without any signs of infection, such as cough or diarrhea. Twelve-lead electrocardiograms (ECGs) indicated ST-segment and T-wave dynamic changes in the inferior and anterior leads. The peak troponin I level was 0.81 ng/mL (normal range < 0.03). A transthoracic echocardiogram (TTE) showed hypokinesis of the apical and mid-distal segments of the left ventricle with a reduced ejection fraction of 48%. A coronary angiogram showed no evidence of coronary artery disease. The patient was discharged home on diltiazem and an angiotensin-converting-enzyme inhibitor (perindopril) with a suspected diagnosis of coronary artery spasm. The TTE demonstrated completely normal cardiac structure and function with an ejection fraction of 68% on July 27, 2018. On August 9, 2018, the patient presented with chest pain again following the same emotionally stressful event (quarrel with her husband). The peak troponin I level was 0.338 ng/mL. The 12-lead ECG indicated ST-segment depression in the inferior leads and T-wave inversion in the inferior and anterior leads. The TTE showed hypokinesis of the apical and mid-distal segments of the left ventricle (ejection fraction of 52%). A coronary angiogram was performed again without evidence of coronary artery disease. A left ventriculogram was not performed again. The patient was discharged with trimetazidine and an angiotensin-converting-enzyme inhibitor (perindopril). On February 9, 2019, the patient presented with similar chest pain following another stressful event (business failure) without any signs of infection.
The patient had a history of pacemaker implantation.
The patient had a free personal history. The patient had no family history of premature coronary artery disease.
Vital signs were stable. There was no obvious abnormality during pulmonary or cardiac examination. There was no jugular vein engorgement or peripheral edema.
The peak troponin I level was 2.228 ng/mL (normal range < 0.03), and the peak B-type natriuretic peptide level was 166 pg/mL (normal range < 76).
Twelve-lead ECGs indicated ST-segment and T-wave changes in the inferior and anterior leads (Figure ). The TTE showed hypokinesis of the apical and mid-distal segments and a hyperdynamic basal segment of the left ventricle with a depressed ejection fraction of 47% (Figure ). Myocardial perfusion single photon emission computed tomography imaging (resting state) demonstrated decreased uptake in the left ventricular apical, anterior, inferior and lateral walls of the myocardium (Figure ). Adrenal computed tomography and hormone results excluded pheochromocytoma. She had no evidence of coronary artery disease detected by the coronary angiogram; however, the left ventriculogram revealed apical akinesia with ballooning of the apical region and hypercontractile basal segments consistent with the typical diagnosis of TCM (Figure ).


The first case was an 8-year-old male Staffordshire Bull Terrier weighing 22.3 kg diagnosed with a lung tumor. A right-sided thoracotomy was performed at the sixth intercostal space for right caudal lung lobectomy. The dog was premedicated with dexmedetomidine (Dexdomitor®; Orion Pharma, UK) 1 μg/kg and methadone (Comfortan®; Dechra, UK) 0.2 mg/kg IV. Anesthesia was induced with propofol (PropoFlo®; Zoetis, UK) 2.7 mg/kg and lidocaine (Lidocaine Hydrochloride; Hameln, UK) 0.9 mg/kg IV and maintained by total intravenous anesthesia (TIVA) of propofol (Fresenius Propoven®; Fresenius Kabi, UK) at 0.1–0.2 mg/kg/minute. The dog was positioned in left lateral recumbency with the uppermost thoracic limb extended cranially. After clipping and aseptic skin preparation, UGSPB was performed. The linear ultrasound probe (5–13 MHz; SonoScapeTM, Shenzhen, China) was positioned perpendicularly to the long axis of the ribs over the mid-dorsal chest at the level of the fourth and later fifth intercostal space. The plane between the EIM and SVM was identified (). Using a 22 gauge, 38 mm hypodermic needle (Terumo®; Hamburg, Germany), levobupivacaine (Chirocaine®; AbbVie, UK) 0.25%, 1 ml/kg was injected using an in-plane technique. The first injection was performed at the level of the fourth intercostal space and the second at the level of fifth intercostal space (0.5 ml/kg at each site), as described by . Each time, hydro-dissection of the fascial plane (FP) was seen and interpreted as correct placement of the needle tip.


Case 2 was a 10-year-old male Labrador Retriever with a body weight of 38.9 kg who was diagnosed with a left cranial lung lobe nodule and a heart base tumor. The dog underwent a right fourth intercostal space thoracotomy for left cranial lung lobectomy and subtotal pericardiectomy. Dexmedetomidine 1 μg/kg and methadone 0.2 mg/kg were administered IV as premedication. Anesthesia was induced with propofol 3 mg/kg IV and maintained with propofol TIVA (0.3–0.4 mg/kg/minute). The UGSPB was performed as previously described with 1 ml/kg of 0.25% levobupivacaine.


The third case was a 9-month-old male Cavalier King Charles Spaniel weighing 8.0 kg who, following traumatic chest injury, underwent a right fifth intercostal space exploratory thoracotomy for rib repair surgery. The dog was premedicated with methadone 0.1 mg/kg IV. Anesthesia was induced with propofol 3.8 mg/kg IV and maintained with Isoflurane (IsoFlo®; Zoetis, UK) vaporized in oxygen (end-tidal Isoflurane 1.2%–1.3%; Wato EX-65; Mindray, China). The UGSPB was performed with 1.2 ml/kg of 0.125% levobupivacaine.


Case 4 involved an 11-year-old female Yorkshire Terrier with a body weight of 4.1 kg who underwent a left-sided fifth intercostal space thoracotomy for subtotal pericardiectomy due to the recurrent pericardial effusion. The dog was premedicated with methadone 0.1 mg/kg IV, and anesthesia was induced with midazolam (Hypnovel®; Roche, UK) 0.2 mg/kg and alfaxalone (Alfaxan®; Jurox, UK) 1 mg/kg both given IV and maintained with Sevoflurane (SevoFlo®; Zoetis, UK) vaporized in oxygen (end-tidal Sevoflurane 2.2–2.3%). The UGSPB was performed with 1.9 ml/kg of 0.15% levobupivacaine.
Intraoperative nociception is defined as 20% increase in the heart rate or blood pressure values in comparison to baseline (). Such a nociceptive response would require rescue analgesia. Patients reported here had changes in heart rate and blood pressure of less than 10% throughout the surgical procedure. Thus, none of them received rescue analgesia. In addition, hemodynamic stability was maintained during surgery and intraoperative hypotension (mean arterial blood pressure ≤ 65 mmHg), measured invasively, was not detected in any of the presented cases (). Besides, no complications were identified from UGSPB performance. All dogs had smooth anesthetic recovery. Postoperatively, dogs were pain scored using the short form Glasgow Composite pain scale every 2 hours for 24 hours. Postoperative analgesia aimed to maintain the pain score below 6/24. This was managed differently among the patients due to the different recommendations given by the different anesthetists responsible for the cases. Cases 3 and 4 received methadone (0.1–0.2 mg/kg) IV every 4 hours and interpleural levobupivacaine 1 mg/kg every 6 hours, both drugs regardless based on the pain scores. Cases 1 and 2 received methadone only when the pain scores were ≥ 6/24. Non-steroidal anti-inflammatory agents were given to all patients. Robenacoxib (Onsior®, Elanco, Germany; 1 mg/kg) PO q24h in the first case and meloxicam (Metacam®, Boehringer Ingelheim, Germany; 0.1 mg/kg) PO q24h in the remaining cases.


A 1-year-old, 22 kg, male castrated Catahoula Leopard dog was referred to the University of Florida Small Animal Hospital (UF SAH) for evaluation of an intermittent left thoracic limb lameness. Four months prior to referral, the dog was hit by a car and sustained a left scapulohumeral luxation. Digital radiographs (AGFA CR30-x generator, with CR MD4.0T plates) of the left thoracic limb were obtained by the referring veterinarian on the day of the initial injury. The left humeral head was laterally and slightly cranioproximally luxated from the glenoid fossa of the scapula ().
The luxation was reduced and the left thoracic limb was immobilized in flexion using a Velpeau sling. Carprofen (Rimadyl, Zoetis) was administered at a dose of 2.2 mg/kg PO every 12 hours for 14 days and the owner was advised to markedly restrict the dog’s activity for 3 weeks. Unfortunately, the humeral head could be palpated cranially to the scapula the following day. The luxation was again reduced and a Velpeau sling was reapplied, but the luxation recurred. This sequence of events was repeated five times over the subsequent 7 days because of recurrence of the luxation. A Spica splint was then applied following closed reduction and the splint was maintained for 1 week. The luxation recurred following splint removal and no further coaptation was applied. The scapulohumeral joint would intermittently luxate and the dog would not bear weight on the limb when the luxation occurred. The owners could readily reduce the luxation and the dog would resume weight-bearing on the limb. Two months after the initial injury, the owner surrendered the dog because of financial concerns. The dog was adopted and was primarily confined in a crate; however, the dog’s left scapulohumeral joint would luxate multiple times each day. The dog would not bear weight on the limb when the luxation recurred, holding the manus proximal to the shoulder with the elbow and carpus flexed. The owner was able to manually reduce the luxation if the luxation did not spontaneously reduce. The dog seemed comfortable and ambulated normally on the limb when the joint was reduced.
At the time of presentation to the UF SAH, the dog ambulated without apparent lameness. During the orthopedic examination, flexion of the dog’s left scapulohumeral joint resulted in cranial displacement of the humeral head causing the dog to maintain the limb in a flexed position. The luxation was readily reduced by extending the scapulohumeral joint and applying traction to the limb. The dog appeared agitated when the joint was luxated, but resumed normal behavior and use of the left thoracic limb when the humeral head was manually reduced.
The dog was sedated with dexdomitor 300 mcg IV and butorphanol 0.1 mg/kg IV, and radiographs of the left scapulohumeral joint were obtained (Canon Imaging System, CXDI-50G digital radiography detectors, UF SAH). The left scapulohumeral joint was congruent and abnormalities were limited to mild, smoothly margined osseous proliferation present on the lateral margin of the glenoid cavity, which was thought to represent an enthesophyte formation at the origin of the lateral glenohumeral ligament. Radiographs were not obtained when the luxation was present.
Open surgical reduction and stabilization (; ) was recommended. The dog was premedicated using dexdomitor 300 mcg IV and butorphanol 0.1 mg/kg IV, perioperative cefazolin was given at 30 mg/kg IV and continued Q 8 hours for 24 hours. Anesthesia was induced with 7.6 mg/kg Propofol given over 60–90 seconds to allow intubation, where anesthesia was maintained with Isoflurane. The left thoracic limb was clipped and prepared for aseptic surgery. The dog was positioned in dorsal recumbency and a craniolateral approach to the left scapulohumeral joint was done. During the initial stages of the procedure, the humeral head intermittently luxated cranially, predominately when the scapulohumeral joint was flexed. The acromial head of the deltoid and the sternocephalicus muscles were retracted and the infraspinatus, superficial pectoral, and deep pectoral muscles were incised and reflected to expose the joint capsule. The cranial joint capsule was circumferentially incised to expose the tendon of origin of the biceps brachii muscle and the transverse humeral ligament was incised. An osteotomy of the greater tubercle of the humerus was performed with an oscillating saw, allowing proximal reflection of the supraspinatus muscle. A pneumatic drill and burr were used to create a trapezoidal proximal-to-distal trough centrally in the exposed cancellous bone in the base of the osteotomy site. The trough was sculpted to conform to the dimensions of the bicipital tendon including the proximal myotendinous portion of the biceps brachii muscle (). The biceps brachii tendon was levered laterally into the trough using a Freer periosteal elevator and the humerus no longer luxated when the bicipital tendon was positioned in the trough (). The joint capsule was reopposed using 2-0 PDS placed in an interrupted cruciate pattern which prevented displacement of the tendon. To augment the stability afforded by the capsulorrhaphy, a six-hole 2.0 mm locking compression plate (DePuy Synthes, West Chester, PA) was placed along the craniolateral margin of the distal scapulohumeral joint line. The plate bridged the bicipital tendon and was secured to the humerus with three locking and one cortical 2.0 mm screws (). The greater tubercle was then repositioned on the incised surface of the humerus, 1 cm distal to the tubercle’s original location. The tubercle was secured with two 1.6-mm Kirschner wires and two strands of 18-gauge orthopedic wires placed in a figure-of-eight configuration as a tension band. Five additional 1.6-mm Kirschner wires were placed to further secure the tuberosity to the proximal humerus (). The remainder of the wound was closed in a routine fashion. After obtaining post-operative radiographs (), the left thoracic limb was placed in a Spica splint (). Postoperatively, the dog was administered methadone (0.1 mg/kg IV Q 4 hours for two doses), transitioned to tramadol (3.3 mg/kg PO Q 8, beginning the morning following surgery), carprofen (16 mg/kg PO Q 12, beginning in the morning following the surgery), trazodone (3.3 mg/kg PO Q 8, beginning in the evening following the surgery), cefazolin continued (30 mg/kg IV Q 8 for 24 hours), transitioned to cephalexin (33 mg/kg PO Q 12, beginning in the evening following the surgery) and continued through discharge for 14 days.
The dog was discharged 2 days following the surgery and the owner was instructed to restrict the dog’s activity, which consisted of confining the dog to a crate or small room in the house when unattended and taking the dog outside for short walks on a leash, mainly for the purposes of urination and defecation. The dog was in a moderate amount of discomfort, which improved with the administration of carprofen and tramadol, for the first 3 days at home. The dog subsequently became more comfortable, but the dog did not effectively use the limb while the Spica splint was in place.
The dog was reevaluated at the UF SAH 2 weeks following the surgery and the Spica splint was removed. The left scapulohumeral joint was stable and could not be luxated. Manipulation of the left scapulohumeral joint was mildly painful. Flexion and extension of the joint was markedly reduced. The left carpus was placed in a carpal flexion bandage () for an additional 10 days to encourage movement in the left scapulohumeral joint but prevent weight-bearing on the limb. The dog was evaluated again at the UF SAH 4 weeks following the surgery. The dog remained predominately non-weight-bearing on the left thoracic limb after removal of the carpal flexion bandage, although the dog intermittently rested the dorsum of the left manus on the ground while standing. Radiographs of the left scapulohumeral joint were obtained under sedation (dexdomitor 325 mcg IV and butorphanol 0.1 mg/kg IV). The left scapulohumeral joint was congruent and there were no complications noted with the surgical implants. Flexion and extension of the left scapulohumeral joint was mildly improved. Extension of the left elbow was also noted to be decreased. A gradual return to normal activity was recommended and the dog was referred to the UF Integrative Medicine Service for rehabilitative therapy. A multimodal rehabilitative approach was implemented with a focus on gait retraining, strength building, and increasing shoulder and elbow joint range of motion. This was achieved through the use of underwater treadmill therapy, photobiomodulation, therapeutic ultrasound, and manual therapy. The dog was seen weekly for formal rehabilitation session with the owner performing prescribed therapeutic exercises at home between sessions. Supplementation with nutraceuticals including fish oil and a combination joint health product including glucosamine, chondroitin, methylsulfonylmethane, and avocado soybean unsaponifiables (Dasuquin, Nutramax) was initiated. By 8 weeks following the surgery, the dog had regained substantial use of the left thoracic limb and was weight-bearing during all gaits, although still moderately lame. Following each integrative therapy session, the dog was more consistently weight-bearing with a greater range of motion in the left scapulohumeral joint. The exercises and range of motion movements were continued at home for an additional month, after which time the dog resumed most normal activities including running walking 5–8 km per day and swimming with only nominal lameness.
The dog was reexamined at the UF SAH 14 months following the surgery to obtain long-term functional results of the procedure (). The owner reported the dog had resumed all normal activities without lameness. On examination, the dog ambulated without appreciable lameness. The dog was walked over a force platform (Model# OR6-6-1000; Advanced Mechanical Technology, Newton, MA) and mild asymmetry between the thoracic limbs was recorded. The peak vertical force (100*N/kg body weight) and vertical impulse for the left thoracic limb were 5% and 6% lesser than the right thoracic limb. The left scapulohumeral joint was comfortable on palpation and could not be luxated. The dog was sedated (dexdomitor 350 mcg IV and butorphanol 0.1 mg/kg IV) and radiographs of the left scapulohumeral joint were obtained (). The left scapulohumeral joint was congruent and there was minor osteophyte formation on the caudal and lateral aspects of the glenoid cavity. Three out of the four bone screws engaging the bone plate along the proximal humerus had broken; there was moderate sclerosis of the humeral head and neck; and the humeral cortex at the level of the third most distal screw was irregularly marginated, decreased in mineral opacity, and ill-defined. The greater tubercle osteotomy had obtained union. While sedated, left forelimb circumference and joint flexion and extension angles were measured. There was mild muscle atrophy of the left thoracic limb: the circumference of the left brachium was 22.3 cm (right: 23.1 cm) and the left antebrachium was 14.1 cm (right: 14.5 cm). While flexion of the left scapulohumeral joint was now equal to the right (both 37°), extension of the left scapulohumeral joint was improved (145°), but still limited as compared to the right (170°). Extension (152°) and flexion (18°) of the left elbow had also improved and were comparable to the right elbow (extension 161°; flexion 16°).


A 66-year-old male patient presented to our Cath Lab for coronary angiography after having a positive dobutamine stress ECHO scan (large area of ischemia on the left anterior descending (LAD) artery territory with underlying good left ventricular systolic function). He had a past history of hypertension and hypercholesterolemia.
Coronary angiography [] showed a severe lesion in the proximal LAD artery with mild plaques in other coronaries. Therefore, a decision was made to proceed with stenting of the proximal LAD.
Using a right radial approach, the left main stem was cannulated by using a 6F Q4 guide catheter and an ASAHI SION blue guidewire was advanced into the distal LAD. The lesion was predilated with 2.5-mm and 3.0-mm noncompliant (NC) balloons; then, it was stented with a 3.5 × 20 mm Supraflex Cruz stent []. However, during stent optimization, there was an initial difficulty to cross through the middle portion of the stent with a 3.75 × 10 mm NC balloon, but after several attempts and with the help of a balance heavy weight guidewire the balloon was placed in the middle of the stent and inflated multiple times up to 18 atmospheres (ATM). Despite repeated postdilatations of this mid-stent segment [], there was a persistent waist of the balloon and the CLEARstent tool illustrated a severely underexpanded stent. Optical coherence tomography (OCT) revealed a marked stent underexpansion (minimal luminal area (MLA) 1.0 mm2) due to a thick circumferential layer of calcium just deep to the stent [].
Super high-pressure non-compliant balloon (OPN NC) was initially considered for further postdilation, but due to high risk of perforation a decision was to try an alternative method. Despite the little documented experience regarding the use of IVL within stent underexpansion as well as the concerns about a potential adverse interaction between IVL and recently implanted stents, we decided to proceed with IVL as it seemed to be the safest approach within this scenario.
Although the guidelines for IVL suggest vessel size: balloon ratio of 1:1, we decided to use a smaller sized balloon based on the very small MLA, at the underexpanded segment, measured by OCT as well as the fact that IVL is a slightly bulky balloon and we had concerns that it might be difficult for a 3.5 IVL balloon to cross such tight stenosis. Therefore, a 2.5 x12 mm lithotripsy balloon (Shockwave Medical, Fremont, CA) was positioned across the underexpanded segment of the stent and inflated to 4 ATM; then, 10 shockwave pulses were delivered at a rate of 1 pulse per second, after which the balloon was inflated further to 6 ATM for 5–10s []. This was repeated five times, thus delivering a total of 50 pulses. Of note, initially there was a waist within the lithotripsy balloon, but surprisingly after only four pulses the balloon suddenly expanded and was no longer waisted. Repeated angiography showed better stent expansion, and further postdilatation was performed with a 4.0-mm NC balloon []. Complete stent expansion was confirmed by repeat OCT []. The patient was doing well at the three-month follow-up in the cardiology clinic.


A male 42-year-old professional medium-sized vehicle driver complained of low-grade fever with a runny nose on 15 May 2020 (day 1 of illness) that lasted for 5 days and subsided upon taking antipyretic and anti-allergic medications. Subsequently, he gradually developed symptoms suggestive of COVID-19, such as anosmia (15–25 May 2020), loss of taste (16–23 May 2020), generalized fatigue (17 May–16 June 2020), and dry cough (22–30 May 2020). He had no history of breathing problems, diarrhea, or eye presentations such as redeye, tearing, foreign bodily sensations, or any other illness (). On 21 May 2020 (day 7 of illness), his nasopharyngeal swab (NPS) specimen tested positive for SARS-CoV-2 RNA. He then underwent strict home isolation and continued it until his SARS-CoV-2 RNA test results were negative. Routine physical examination revealed that all parameters were within normal limits, except for slightly increased systolic blood pressure (130 mmHg) and obesity (body mass index (BMI): 32.8 kg/m2). Previous laboratory reports showed dyslipidemia and fatty changes in the liver upon ultrasonography of the hepatobiliary system (with occasional lipid-lowering drugs). Other parameters were within normal limits ().
His symptoms were managed both at home and with medications. Under home management, he followed hot steam inhalation, gargling with warm water, took herbal tea and lemonade, drank warm water with food, and occasionally performed freehand exercises. During this time, he took azithromycin, bromhexine hydrochloride, and cough-suppressant combinations (dextromethorphan + pseudoephedrine + triprolidine), ivermectin, and doxycycline. His COVID-19-related symptoms had resolved by day 17 (31 May 2020), except for mild fatigue that persisted for another 16 days. On day 22, his second COVID-19 test was positive for SARS-CoV-2 RNA and he continued home isolation accordingly. After clinical recovery, he was symptom-free but had an occasional nonspecific headache. He was non-diabetic based on a previous medical report, but routine checkup on 4 July 2020 revealed raised plasma sugar levels in fasting and 2-h postprandial glucose challenges. He started anti-diabetic medications (glimepiride and metformin hydrochloride) under an endocrinologist. On 25 July 2020 (day 72 of illness), 22 days after initiating anti-diabetic medication, he finally tested negative for SARS-CoV-2 RNA. Upon further follow-up (5 August 2020), plasma glucose monitoring revealed controlled glycemic status, but he had dyslipidemia with moderate fatty infiltration in the liver, for which he took appropriate measures. Throughout, he had no breathing problems and did not require anti-viral drugs or hospital admission. The entire illness period, PCR (polymerase chain reaction) testing, and medication profile are described in and .
His wife had also been detected with COVID-19 on 23 May 2020 and tested negative for SARS-CoV-2 on 4 June 2020 and was asymptomatic throughout her illness. Fortunately, none of the children were infected with COVID-19.


A 40-year-old male farmer reported with complaints of swelling over right side of floor of mouth and pain during meals for around 2 years and protrusion of stone-like structure from floor of mouth for the last 2 days. The swelling over floor of mouth had gradually increased in size and for the past 2 days patient started experiencing excessive salivation and a pale-yellow coloured swelling became visible over right side of floor of mouth. Patient's medical history was insignificant. Extraoral examination showed no significant findings. Intraoral examination showed a pale-yellowish stony hard structure protruding from right Wharton's duct orifice []. There was clear mucoid discharge seen from the duct. Rest of the oral cavity was unremarkable. The orthopantomogram was done and reported as single crescent-shaped radiopaque calculus superimposed over right canine, molars and right mandible extending from midline to distal molars over the edentulous ridge suggestive of right submandibular sialolithiasis []. The stone extraction with marsupialization of duct was done under local anaesthesia. The procedure was uneventful. Stone measured 42 mm in size and 15 gram in weight. [] which is one of the largest reported in medical literature. After a year in follow up patient is asymptomatic.


A 76-year-old female with multiple comorbidities including scleroderma, chronic anemia, fibromyalgia, hypertension, chronic kidney disease stage 3, interstitial lung disease on 3 L oxygen, Raynaud’s phenomenon, inflammatory bowel disease, hypothyroidism presented to the hospital with black discoloration of right second and third toe. She was started on intravenous linezolid and cefepime for presumed necrosis of toes. Arterial duplex study ruled out acute ischemia of lower extremities. On third day (55 h) of admission, she had a change in her mental status. She was agitated and disoriented on examination. Neurological exam revealed 3+ reflexes on bilateral lower extremities along with clonus and increased muscle rigidity. Blood pressure was 131/75 mmHg, Heart rate 104/min, respiratory rate 20/min, oxygen saturation 98% on 3 L oxygen, temperature was 36°C at the time but increased to 38.1°C few hours later.
Computed Tomography (CT) of the head was done which was unremarkable. Upon reviewing the home medications with the husband, we found that she was chronically on tramadol, cyclobenzaprine, oxycodone, pantoprazole and amlodipine. In the hospital, in addition to Linezolid, she was on metoclopramide as well. Though the presentation was atypical, we suspected serotonin syndrome (SS) based on Hunter’s Criteria. Acute delirium was ruled out after determining no acute electrolyte abnormalities, drug overdosing, substance abuse, and acute alcohol or opiate withdrawal. Her metoclopramide and linezolid were stopped, and the antibiotic was switched to vancomycin. CT head was repeated in next 24 h which was again unremarkable. Magnetic Resonance Imaging (MRI) of the brain did not reveal any acute pathology. Cerebrospinal fluid (CSF) cell count was within normal limits, with normal protein and negative gram stain and culture. Herpes simplex virus 1 & 2 PCR, cryptococcus antigen, varicella antibody, measles antibody, mumps antibody, rubella antibody, and West Nile virus antibody were negative. Serum Human Immunodeficiency Virus (HIV) ELISA test was non-reactive for HIV 1 & 2. Her laboratory results are tabulated in . The patient was managed on the telemetry floor with frequent mental status assessment and intravenous lorazepam as needed for agitation. On fourth day of stopping Linezolid and metoclopramide, her mental status started to improve. Her clonus and hyperreflexia resolved. A day later, the mental status returned to baseline. Her gangrenous change was deemed to be a dry gangrene due to chronic ischemia secondary to Raynaud’s phenomenon and thus antibiotics were stopped. She had full mental and neurological recovery as was discharged on day 8 of hospitalization. Her tramadol and cyclobenzaprine were stopped on discharge (timeline depicted in ).


A 68-year-old woman was referred to our emergency department for the onset of an acute severe chest pain irradiated to the interscapular regions and to both arms lasting about 2 h. She had diabetes mellitus, hypertension, and former smoking as cardiovascular risk factors. Another relevant comorbidity was a mixed anxiety-depressed disorder under pharmacological treatment. She also reported a recent intense emotional stress. The patient appeared comfortable, with unlaboured breathing. The temperature was normal, the pulse 100 b.p.m., the blood pressure 140/90 mmHg, and the oxygen saturation 97% while she was breathing ambient air. No clinical signs of heart failure were present. High-sensitivity Troponin I levels were increased (i.e. 0.198 and 3.896 ng/mL in two consecutive samples, reference range <0.04 ng/mL). Electrocardiogram (ECG) showed sinus rhythm, signs of left ventricular hypertrophy and aspecific ST-T-wave abnormalities (Figure ). After excluding an acute aortic syndrome by emergent chest computed tomography angiography a diagnosis of ACS was made, and was admitted to the Cardiology unit.
Baseline coronary angiography revealed non-obstructive coronary artery disease, and an intramyocardial bridge of the mid-left anterior descending (LAD) coronary artery (). Left ventriculogram showed a preserved global left ventricle function and an inferior focal akinesia with basal and apical hyperkinesis ( and , ). Based on the clinical and angiographic findings, a diagnosis of ‘focal’ TTS was made. Trans-thoracic echocardiography revealed a regional hypokinesia of the inferior mid-basal wall and septum. A cardiac magnetic resonance imaging was attempted to better define the cardiomyopathy findings, which the patient was not able to perform due to severe claustrophobia. Eventually, the patient was discharged with Bisoprolol 5 mg daily, Ramipril 2.5 mg daily, and Aspirin 100 mg daily planning a clinical follow-up at 3 months.
However, 2 months later, the patient came back to the emergency department of our institution with recurrent chest pain and dyspnoea arising 3 h before. During the medical interview, she referred a newly emotional stress has been occurred. Physical examination and ECG were unchanged compared with the previous episode. N-terminal pro b-type natriuretic peptide was 244 pg/mL (normal values <150 pg/mL) and hs-TnI levels were abnormal with a rise-and-fall pattern. InterTAK score, which takes into account both clinical and diagnostic findings, was 60 reflecting a probability of a recurrence of TTS of 54%. Echocardiographic evidence of hypokinesis of the inferior septum, basal inferior wall, and mid-apical infero-lateral walls was reported.
Coronary angiography showed an irregular subocclusive stenosis of a well-developed first obtuse marginal branch (, ). However, after administration of intracoronary nitroglycerine, a complete recover of the vessel patency was noted, and a diagnosis of epicardial spasm was made (, ). Due to the persistence of a mild residual stenosis with focal area of angiographic ‘haziness’, intracoronary optical coherence tomography (OCT) imaging was performed which confirmed a normal vessel morphology ( and ) and a residual focal area of spasm without any signs of instability (). Left ventriculogram showed an improved left ventricular function with only a mild residual hypokinesia of the inferior mid-ventricular wall, significantly improved compared with the previous exam ( and , ). Pre-discharge echocardiography revealed a full recovery of the regional wall motion abnormalities observed during both episodes ().
Based on these new findings, medical therapy was optimized by adding Amlodipine 5 mg daily, and the patient was discharged. No further events occurred after 1 month of follow-up.


A 79-year-old man was initially admitted to The First Affiliated Hospital of Shandong First Medical University in February 2012, complaining of the loss of appetite and weakness for nearly 3 months. Twenty years ago, he was diagnosed with sigmoid adenocarcinoma and received surgery and postoperative adjuvant chemotherapy. He had no history of any hepatitis virus infection. He had a long history of alcohol consumption, but not gastrointestinal bleeding. On admission, the liver was not touched by physical examination. The platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), and liver function tests including alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) were normal (). He also had normal levels of alpha fetoprotein (AFP) and SCC antigen, but the levels of cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) were elevated. Computed tomography (CT) revealed multiple low-density lesions with unclear boundary and mild to moderate enhancement in the liver accompanied by liver cysts and gallbladder stones, without portal vein invasion or splenomegaly ( and ). Ultrasonography (US)-guided liver biopsy showed a pathological diagnosis of SCC by hematoxylin-eosin (HE) staining. IHC analysis showed that CK7, hepatocyte and CK19 staining were negative but p63 expression was positive (–). Ventana IHC analysis (Clone NO. SP263) indicated that PD-L1 expression on tumor cells and tumor-associated immune cells was negative ( and ). Given that no lesions in the lungs, gastrointestinal tract or other organs were observed, primary SCC of the liver was diagnosed. The patient did not receive surgery, radiotherapy, transarterial chemoembolization (TACE), or tyrosine kinase inhibitor treatment. He was treated with SOX chemotherapy regimen (Oxaliplatin 200 mg, day 1, and S-1 50 mg twice per day, d1-14, q21d) for 4 cycles. However, the patient stopped his therapy 3 months later. Subsequently, his disease progressed, and he rejected any anticancer therapies and died at the 20th month of the initial diagnosis.


A 47-year-old man complained of pain in the right upper region of the abdomen after drinking in October 2016. He had a history of hepatitis B but not C virus infection. He also had a long history of alcohol consumption but denied gastrointestinal bleeding history. Physical examination revealed a deep tenderness in his upper abdomen. His blood routine examination and coagulation function were normal. Liver function test showed an obvious increase in ALT, AST but TBIL and DBIL were negative. On admission, he had normal levels of AFP and CEA (). An abdominal CT scan conducted in a local hospital demonstrated a single, big and solid lesion with a diameter of 10 cm, with mild to moderate enhancement in the parenchymal part of the tumor edge. There were no lesions in his lungs, gastrointestinal tract and other organs, indicating an initial disease with localized stage. At that time, a right hepatectomy with cholecystectomy was performed when a large lesion was found in the right lobe of the liver. The final pathology report revealed a diagnosis of primary SCC of the liver through routine HE () and IHC analysis ( and ), with chronic cholecystitis. There were no stones in the bile ducts and gallbladder. The negative staining of CK7 (), positive staining of p63 (), hepatocyte and CK19 indicated the squamous epithelium origin of the tumor. Positive PD-L1 staining on tumor cells but not on tumor-associated immune cells was observed ( and ). This patient recovered well and was consistently treated with TACE and two cycles of adjuvant chemotherapy (gemcitabine combined with 5-fluorouracil). He did not undergo radiotherapy or other therapies. This patient has a long survival time of up to 35 months and still is alive until now.


In July 2019, A 79-year-old woman came to our hospital and presented with abdominal pain, nausea, fever and weight loss over the past 3 months. She did not have a history of hepatitis virus infection, hepatic cyst, chronic cholecystitis or hepatolithiasis. Other medical history was negative. Hematological analysis revealed liver function was normal (). The levels of CEA and AFP were normal but serum ferroprotein and SCC antigen were slightly elevated. Enhanced magnetic resonance imaging (MRI) revealed a large mass in the right lobe of the liver (7.5 × 6.0 × 5.6 cm), with a long T1 and long T2 signal, a high signal in diffusion-weighted image (DWI), and a low signal in apparent diffusion coefficient (ADC). The lesions invaded the adjacent ascending colon and surrounding peritoneum (–). A US-guided fine-needle aspiration biopsy of the mass confirmed a pathological diagnosis of SCC with a histological feature of keratinization (–). IHC analysis indicated that the expression of PD-L1 on tumor cells was 30%, and its expression on tumor-associated immune cells was 10% ( and ). Both chest CT and gastrointestinal radiography reported negative findings. Therefore, a final diagnosis of primary SCC of the liver was made. Unfortunately, due to the poor performance status, the patient only received tyrosine kinase inhibitors anlotinib monotherapy and died of dysfunctions of the liver and kidneys 2 months later.