High-altitude pulmonary edema (HAPE) is a life-threatening, noncardiogenic pulmonary edema that occurs in unacclimatized individuals rapidly ascending to high altitudes above 2,500 m above sea level. Until the entity of HAPE was first identified in a case report published in Japan in 1966, the symptoms of severe dyspnea or coma occurring in climbers of the Japan Alps were incorrectly attributed to pneumonia or congestive heart failure. The Shinshu University Hospital serves as the central facility for rescuing and treating patients with HAPE in the region. Over the past 50 years, a series of studies have been conducted at Shinshu University to gain a better understanding of the characteristics of HAPE. This review summarizes the major achievements of these studies, including their clinical features, management, and pathogenesis of HAPE, particularly in the Japanese population.

Objective Radwisp™ is a fluoroscopic video analysis workstation recently developed to evaluate pulmonary circulation, thereby obviating the need for contrast medium or breath-holding. This study validated Radwisp as a diagnostic tool for acute pulmonary embolism (APE) and evaluated its potential utility in patients with symptoms of suspected APE.

Methods The study included 10 patients (mean age, 69±16 years old) who were admitted to our hospital for suspected APE based on symptoms and physical examination findings between January 2020 and April 2021. Contrast-enhanced computed tomography (CT) and cineradiography, based on standard radiographs for the creation of a Radwisp image, were performed on the same day. Of the 10 cases of suspected APE, 7 were definitively diagnosed by CT with APE, and 3 were definitively diagnosed as not having APE. Fifty physicians (25 cardiologists and 25 residents) were blinded to patient information and CT images and asked to diagnose the presence of APE based solely on the Radwisp images.

Results A total of 250 diagnoses were made by cardiologists and 250 by residents. Among the cardiologists, the sensitivity and specificity of the Radwisp-based analysis were 91% and 48%, respectively, and the positive and negative predictive values were 80% and 69%, respectively. Among the residents, the sensitivity and specificity were 88% and 35%, respectively, and the positive and negative predictive values were 76% and 55%, respectively.

Conclusion This study showed an initial validation of Radwisp for diagnosing APE, revealing a high sensitivity but not yet achieving a high specificity. Further studies with a larger number of cases are needed to thoroughly evaluate the diagnostic performance.

Objective Earlobe crease (ELC) is an easily detectable physical sign of cardiovascular risk and coronary artery disease (CAD). However, the relationship between ELC and CAD severity in patients with ST-segment elevation myocardial infarction (STEMI) requiring urgent clinical judgment is unknown. Using the residual synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score, we investigated the relationship between ELC and anatomical severity of CAD.

Methods We studied 219 consecutive patients with STEMI (median age, 71 years old) and divided them into 2 groups according to the presence of ELC (ELC group, n=161; non-ELC group, n=58).

Results The ELC group had a significantly higher number of diseased vessels than the non-ELC group (≥2 diseased vessels, 79% vs. 46%; ≥3 diseased vessels, 35% vs. 12%; p<0.001). In addition, a higher median residual SYNTAX score was observed after primary percutaneous coronary intervention than the non-ELC group [8 (4-12) vs. 3 (0-8), p<0.001]. Furthermore, a multivariable regression analysis showed that ELC was an independent predictor of the residual SYNTAX score (β=3.620, p<0.001).

Conclusions The presence of ELC was significantly associated with the anatomical severity of diseased coronary vessels in patients with STEMI who required emergency clinical judgment and treatment.

Objective This study examined whether or not hyperglycemia on admission is associated with poor outcomes in patients with successful reperfusion by mechanical thrombectomy (MT).

Methods Consecutive patients with acute anterior circulation stroke and large-vessel occlusion treated with MT were evaluated. Hyperglycemia was defined as a blood glucose level of >140 mg/dL on admission. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction of grade 2b or 3. A poor clinical outcome 90 days after the onset was defined as a modified Rankin Scale score of 4-6. We compared characteristics, including outcomes, between the normoglycemic (≤140 mg/dL) and hyperglycemic groups. In addition, the association between hyperglycemia and outcomes was evaluated in patients with successful reperfusion using MT.

Results The participants comprised 407 patients [median age, 76.5 years old; 58.0% men; median National Institutes of Health Stroke Scale (NIHSS) score, 17]. The site of occlusion was the Internal Carotid Artery (ICA) in 119 patients (29.2%) and the M1 in 178 patients (43.7%). Normoglycemia, hyperglycemia, successful reperfusion, and poor outcomes were found in 138 (33.9%), 269 (66.1%), 320 (78.6%), and 141 (34.4%) patients, respectively. Poor outcomes were more frequent in hyperglycemic patients (61.6%) than in normoglycemic patients (43.9%, p=0.001). Among patients with successful reperfusion, poor outcomes were more frequent in hyperglycemic patients (57.8%) than in normoglycemic patients (37.9%; p<0.001). In patients with successful reperfusion, a multivariate regression analysis identified hyperglycemia as a factor associated with poor outcomes (odds ratio, 2.151; confidence interval, 1.166-3.970; p=0.014).

Conclusion Among all patients, hyperglycemia on admission was associated with a poor outcome in those treated with MT. Regarding the presence of successful reperfusion by MT, patients with successful reperfusion had such effects.

The misdiagnosis of intestinal tuberculosis (ITB), such as Crohn's disease (CD), and subsequent treatment with immunosuppressive therapies can lead to severe outcomes. However, the differential diagnosis between these two conditions can be challenging. We herein report a patient from Myanmar who was initially diagnosed with CD due to the presence of non-caseating granulomas. The patient's symptoms were aggravated with steroid treatment, eventually leading to a diagnosis of ITB. In the international medical community, we encounter patients from countries, such as Myanmar, where tuberculosis is endemic. Therefore, it is necessary to understand the epidemiological background of each country to accurately distinguish between CD and ITB.

A 54-year-old woman presented with an elevated esophageal lesion. Computed tomography (CT) and magnetic resonance imaging revealed a mass in the pancreatic head. Endoscopic ultrasound (EUS) showed a well-defined, round, hypoechoic mass, which was considered lymph node enlargement. An EUS-guided fine-needle aspiration biopsy (FNAB) was performed on the esophagus and the mass above the pancreatic head. The pathologically confirmed epithelial cells and multinucleated giant cells were positive for T-SPOT. Clinically, tuberculous lymphadenitis and esophageal tuberculosis were suspected, with successful treatment with anti-tuberculosis therapy resulting in a good response. Our findings suggest that an EUS-FNAB is useful for diagnosing esophageal tuberculosis.

A 70-year-old woman was admitted to the hospital 1 month prior to presentation with acute pancreatitis due to pancreaticobiliary maljunction. After discharge, she was referred for elevated hepatobiliary enzyme levels. She was diagnosed with an acute pancreatitis flare-up. Computed tomography revealed dilation of the common duct compared to the previous admission. Considering the protein plug formation as the cause, endoscopic retrograde cholangiopancreatography (ERCP) was performed after improvement. ERCP revealed a defect in the duct, suspected to be caused by protein plugs, which were removed using a balloon after endoscopic papillary balloon dilatation. An analysis revealed that this component was a protein. No recurrence of pancreatitis was observed after the treatment.

Epiphrenic diverticulum is a rare condition commonly diagnosed in middle-aged adults. Symptoms include dysphagia and regurgitation, which are associated with underlying esophageal motility disorders. We herein report a 93-year-old woman with dysphagia diagnosed with symptomatic epiphrenic diverticulum by computed tomography, esophagogastroduodenoscopy, and esophagography. The patient was successfully treated non-surgically without any complications. This case demonstrates that conservative treatment is an option for older high-risk patients.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

A 59-year-old Japanese woman presented with hyperferritinemia. We decided against iron removal treatment because there were no symptoms or signs of iron-induced organ damage. A follow-up study revealed a gradual increase in transferrin saturation. The patient underwent a second examination at 66 years old. A liver biopsy showed substantial iron deposits in hepatocytes and Kupffer cells but no inflammation or fibrosis. Serum hepcidin-25 levels were highly parallel with hyperferritinemia. A genetic analysis revealed a G80S mutation in SLC40A1. These features are compatible with those of ferroportin disease. The patient remained asymptomatic at 70 years old, suggesting that the iron-loading condition may have been benign.

Reports of pancreatic neuroendocrine neoplasm (P-NEN) concomitant with intraductal papillary mucinous neoplasm (IPMN) are gradually increasing. However, many of these cases were diagnosed in the resected specimen incidentally. We herein report a case of minimal P-NEN concomitant with branch-duct IPMN that was successfully diagnosed preoperatively by contrast-enhanced endoscopic ultrasonography (EUS) and an EUS-guided fine-needle biopsy. These findings suggest that P-NEN as well as pancreatic ductal adenocarcinoma should be considered as concurrent tumors developing in patients with IPMNs. EUS is an essential modality when evaluating IPMN for detecting small lesions concomitant with IPMN.

A 67-year-old woman with severe aortic stenosis (AS) was transferred to our hospital for large B-cell lymphoma treatment. Because of her high risk of anthracycline-induced cardiotoxicity due to severe AS and low performance status, the patient was initially treated with doxorubicin-free chemotherapy. However, doxorubicin was considered necessary to achieve complete remission. After multidisciplinary team discussions, transcatheter aortic valve replacement (TAVR) was performed without complications. Nine days after TAVR, the patient received the first cycle of anthracycline-containing chemotherapy (R-CHOP). Currently, 12 months after completing 4 cycles of R-CHOP, the patient remains in complete remission without having developed cardiotoxicity.

An 81-year-old man with hypertension and a history of smoking presented with renal enlargement and progressive renal dysfunction despite no family history of kidney disease. A renal biopsy revealed diffuse tubular, dilated, and atrophic distal tubules with cystic formation and thin irregularities in the tubular basement membrane. Although no known genetic abnormalities were detected, the patient was diagnosed with medullary cystic kidney disease (MCKD). In addition, idiopathic nodular glomerulosclerosis, which is characterized by significant mesangial expansion and accentuated glomerular nodularity and is associated with hypertension and cigarette smoking, was identified as a complication of MCKD. We herein report a rare case of sporadic MCKD with idiopathic nodular glomerulosclerosis.

The Epstein-Barr virus (EBV) is associated with many malignancies and autoimmune diseases, including multiple sclerosis. In addition, EBV rarely but occasionally causes central nervous system (CNS) complications. We herein report a case of transverse myelitis (TM) associated with systemic EBV reactivation after herpes zoster infection in a cord blood transplant recipient. Identification of EBV-infected peripheral blood cells revealed a predominance of B cells. Notably, intravenous rituximab ameliorated EBV reactivation and TM. Since the CNS infiltration rate of intravenous rituximab is markedly low, the clinical efficacy of rituximab against TM suggests that EBV reactivation may cause TM via immune-mediated mechanisms.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by Parkinsonism, cerebellar ataxia, and autonomic dysfunction. While less frequent than Parkinson's disease, MSA patients with a beneficial levodopa response may occasionally present with levodopa-induced dyskinesia (LID). We herein report a 50-year-old woman diagnosed with MSA-parkinsonism who developed LID in the unilateral lower extremity 10 months after the start of levodopa treatment. In this case, the distribution of LID, the timing of its onset, and the presence of LID despite relatively poor levodopa responsiveness were distinctive.

A 78-year-old woman with a history of intractable otitis media presented with a fever, hearing impairment, thigh pain, and a skin rash. She had renal dysfunction, positive myeloperoxidase-antineutrophil cytoplasmic autoantibody, otitis media, and multiple nodules in both lungs. She was diagnosed with granulomatosis with polyangiitis, crescentic glomerulonephritis, and interstitial nephritis, which was confirmed in a kidney biopsy specimen. Induction therapy with rituximab and avacopan without glucocorticoids promptly resolved her fever and thigh pain and improved her auditory acuity and nodule in the right lung. The patient experienced no adverse effects with rituximab or avacopan.

We herein report a case of Mycobacterium interjectum pulmonary disease (M. interjectum-PD) that improved considerably after azithromycin (AZM), rifampicin (RFP), and ethambutol (EB) therapy. A 69-year-old woman, managed locally for suspected NTM-PD based on chest computed tomography (CT) findings was referred to our hospital for worsening productive cough six years after the initial diagnosis. High-resolution chest CT showed right middle and left lower lobe bronchiectasis with middle and centrilobular nodules. Bronchial washing and sputum culture yielded M. interjectum. Treatment with AZM, RFP, and EB resulted in sputum culture conversion, and the chest CT findings subsequently improved. This is the first reported case of M. interjectum-PD in Japan.