Objective Acetylcholine (ACh) use in patients with bronchial asthma (BA) is contraindicated. We examined the clinical usefulness and safety of ACh spasm provocation tests in rest angina patients with BA.

Patients The study subjects were 495 rest angina patients (mean age: 64.4±10.9 years old, male: 81.0%). Organic stenosis was found in 69 patients (13.9%).

Methods We investigated 495 rest angina patients who underwent ACh spasm provocation tests. ACh was injected in incremental doses of 20/50/100/200 μg into the left coronary artery and 20/50/80 μg into the right coronary artery. Provoked positive spasm was defined as transient ≥90% luminal narrowing and usual chest pain or ischemic electrocardiogram changes.

Results Among 495 rest angina patients, 13 (2.6%) were complicated with BA. Eleven patients with BA were controlled under medications, and two patients had a history of medication for BA. The clinical characteristics were not markedly different between rest angina patients with and without BA. The rate of multi-vessel spasm was markedly higher in patients with BA than that in those without BA. No complications during ACh spasm provocation tests were recognized in rest angina patients with BA, whereas major complications in those without BA were observed in eight patients including two ventricular fibrillations, three non-sustained ventricular tachycardias, and three shocks. We were able to perform all 495 ACh spasm provocation tests without any irreversible complications, while electrical defibrillation was necessary for 2 patients without BA.

Conclusion We were able to perform ACh spasm provocation tests in rest angina patients with BA irrespective of the off-label use of ACh.

Objective The burden of death from pneumonia is expected to increase with the aging of the population, as has been observed in Japan. Depressive tendency, a common psychosocial sign, may be a risk factor for pneumonia due to its possible association with some immune dysfunction. This study aimed to clarify the association between depressive tendency and the risk of death from pneumonia.

Methods A population-based cohort that consisted of 75,174 Japanese men and women was followed for a median of 19.1 years. Four psychological and behavioral symptoms (depressive symptoms) were used to evaluate depressive tendency.

Results A total of 1,329 deaths from pneumonia were observed. Depressive symptoms were positively and dose-dependently associated with the risk of death from pneumonia (p<0.001 for trend), and subjects with ≥2 depressive symptoms showed a significantly elevated risk compared to those without any symptoms [multivariable hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.39-1.99]. This association was not significantly affected by sex or age at baseline. The elevated risk was still significant even when subjects were limited to those without any medical histories. The excess risk was observed not only for death occurring within the first 10 years of follow-up (multivariable HR, 2.05; 95% CI, 1.51-2.78) but also for that occurring in the longer follow-up period (multivariable HR, 1.48; 95% CI, 1.18-1.85).

Conclusion Depressive tendency may be a risk factor for death from pneumonia. Further studies using a more reliable tool for the evaluation of depressive state are necessary to confirm this relationship.

Objective In fever clinics screening coronavirus disease (COVID-19), there could be patients with life-threatening diseases that physicians should not overlook. We exploratorily investigated the final diagnosis among non-COVID-19 hospitalized patients who visited the fever clinic.

Methods This was a retrospective, observational, and single-centered study conducted in the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. We conducted a retrospective chart review of patients who visited the fever clinic in the NCGM from 11 March 2020 to 24 April 2020.

Patients Patients who met the following clinical criteria visited the fever clinic in the NCGM: (1) body temperature >37.5°C, (2) any symptoms consistent with COVID-19 or (3) referral from local healthcare facilities. In the fever clinic, all patients who met the above criteria had severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test with nasopharyngeal swab specimens. Patients with severe symptoms or an unstable condition were sent to an outpatient clinic for infectious diseases for further evaluation and treatment.

Results Among 1,470 patients who visited the fever clinic, 84 patients were hospitalized, and 45 of them were diagnosed as having COVID-19. Among the remaining 39 non-COVID-19 patients, there were nine patients with life-threatening diseases. The life-threatening diseases included acute heart failure, septic shock, pneumocystis pneumonia, peritonsillar abscess, and necrotizing fasciitis.

Conclusion Physicians should evaluate each patient carefully while considering other life-threatening conditions even in such a COVID-19 pandemic era.

Objective To describe the clinical features and clinical course of individuals diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild coronavirus disease (COVID)-19.

Patients The study participants consisted of 7 crewmembers of the passenger cruise-liner, Diamond Princess, who were admitted to our hospital after becoming infected with SARS-CoV-2 aboard the ship.

Methods The data on patient background and biochemical test results were obtained from the patients' medical records. All patients had a chest X-ray, and a throat swab and sputum samples were sent for culture on admission.

Results The median age of the 7 patients, of whom 4 were male and 3 were female, was 39 years (range: 23-47 years). On admission, none of them had fever, but 4 (57%) had a cough. None of them showed any signs of organ damage on laboratory testing. Chest X-ray showed pneumonia in one individual, which resolved spontaneously, while the other 6 had normal chest X-ray findings. Culture of throat swabs and sputum samples revealed that 4 patients (57%) had bacterial upper respiratory infections (Haemophilus influenzae, Klebsiella pneumoniae, and Staphylococcus aureus). The period from a positive polymerase chain reaction (PCR) test to negative conversion ranged from 5 to 13 days, with a median of 8 days.

Conclusion Healthy young adults without risk factors who acquire SARS-CoV-2 infection may have an asymptomatic infection or may experience mild COVID-19. In addition to obesity, an older age, underlying illness, and being overweight can lead to a risk of exacerbation; thus, hospital management for such individuals may be desirable. Culturing respiratory samples may be useful for diagnosing secondary bacterial pneumonia.

Objective Empirical evidence on the availability bias associated with diagnostic errors is still insufficient. We investigated whether or not recent experience with clinical problems can lead physicians to make diagnostic errors due to availability bias and whether or not reflection counteracts this bias.

Methods Forty-six internal medicine residents were randomly divided into a control group (CG) and experimental group (EG). Among the eight clinical cases used in this study, three experimental cases were similar to the disease of dengue fever (DF) but exhibited different diagnoses, one was actually DF, and the other four filler cases were not associated with DF. First, only the EG received information on DF, while the CG knew nothing about this study. Then, six hours later, all participants were asked to diagnose eight clinical cases via nonanalytic reasoning. Finally, four cases were diagnosed again via reflective reasoning.

Results In stage 2, the average score of the CG in the diagnosis of experimental cases was significantly higher than that of the filler cases (0.80 vs. 0.59, p<0.01), but the EG's average score in the two types of cases was not significantly different (0.66 vs. 0.64, p=0.756). The EG and CG had significantly different scores for each experimental case, while no difference was observed in the filler cases. The proportion of diseases incorrectly diagnosed as DF among experimental cases ranged from 71% to 100% in the EG. There were no significant differences between the mean diagnostic accuracy scores obtained by nonanalytic reasoning and those obtained by the reflective reasoning in any cases.

Conclusion Availability bias led to diagnostic errors. Misdiagnoses cannot always be repaired solely by adopting a reflective approach.

A 49-year-old man complained of chronic palpitation and shortness of breath, which had recently become exacerbated. A blood examination indicated severe refractory anemia and hypoproteinemia. Physical examinations revealed anemia, a systolic murmur, and spoon nails. Multiple nonspecific ileal ulcers were observed. A pathological examination indicated a small granuloma with CD68-positive histiocytes. He had a deeply wrinkled forehead, chiseled face, and clubbed fingers. Radiography revealed periostosis of the fingers and long bones in the limb. He was diagnosed with pachydermoperiostosis. SLCO2A1 demonstrated a c.1807C>T homo-mutation. He was also diagnosed with SLCO2A1-associated chronic enteropathy and thus was treated with 5-aminosalicylic acid, which temporarily improved the ileal ulcers, anemia, and hypoalbuminemia.

Helicobacter pylori (H. pylori)-negative gastric cancer (HPNGC) usually shows a gastric mucin phenotype, but there are a few case reports of HPNGC with an intestinal mucin phenotype. We herein report a case of multiple HPNGC with an intestinal mucin phenotype showing a gastritis-like appearance. A 68-year-old H. pylori-uninfected man was suspected of having antral gastritis on endoscopy, but a histologic examination revealed multiple well-differentiated adenocarcinomas with positive-CDX2/MUC2/CD10 and negative-MUC5AC/MUC6. P53 was overexpressed, and intestinal metaplasia was sporadically detected in the non-atrophic mucosal background, thus indicating H. pylori-unrelated multistage carcinogenesis. The neoplastic surfaces were covered by a non-neoplastic epithelium, which caused a gastritis-like appearance. This report suggested the possibility of overlooking this neoplasm.

We report a rare case of clival metastasis from gastric cancer. A 73-year-old man with advanced gastric cancer treated with nivolumab as a third-line chemotherapy experienced headache, tongue deviation, and difficulties in speaking clearly. We suspected stroke or brain metastasis, but brain contrast-enhanced magnetic resonance imaging demonstrated a clival mass, diagnosed as clival metastasis from gastric cancer. The tumor could not be identified by plain computed tomography and plain magnetic resonance imaging alone. He received palliative radiotherapy (30 Gy/10 fr); his symptoms improved gradually. Although metastasis from gastric cancer to other organs is common, bone metastases are rare.

An 80-year-old woman presented with a 30-mm protruding lesion-like submucosal tumor with a central depression located at the anterior wall of the upper gastric body. The depressed area had a well-demarcated margin, while the other area was covered by a non-neoplastic mucosa. A biopsy specimen revealed neuroendocrine carcinoma. Endoscopic ultrasonography revealed a heterogeneous mass with a clearly distinguished border in the submucosal layer. The mass had two distinct areas adjacent to each other. In addition, a hypoechoic zone was observed on the margin of the mass. Distal gastrectomy was performed. The final diagnosis was a mixed neuroendocrine-non-neuroendocrine neoplasm arising from the heterotopic gastric gland.

We herein report the histological findings of a patient who had progressed to persistent cardiac arrest for 25 days due to lymphocytic fulminant myocarditis despite mechanical circulatory support (MCS). There were few residual cardiomyocytes, and extensive replacement fibrosis was present. Therefore, improvement of the cardiac function for this patient was considered improbable. Further research is warranted to improve predictions for the recovery of the cardiac function and optimize MCS strategies for patients with fulminant myocarditis.

Although cardiovascular involvement is a well-known complication correlated with a poor prognosis in patients with systemic sclerosis, there are few reports on valvular heart disease. Forty patients with systemic sclerosis were retrospectively analyzed. Valvular heart disease was found in six patients, five of whom had severe tri-leaflet aortic stenosis. Three of these 5 patients were ≤71 years old. Two frail elderly patients who underwent transcatheter aortic valve replacement died within two years.

Premature-onset aortic stenosis is not uncommon in patients with systemic sclerosis. When considering mechanical intervention, the evaluation of frailty is important.

A 77-year-old woman was admitted to our hospital with severe ongoing chest pain. Electrocardiography showed ST-segment elevation in the inferior leads and tall R waves in leads V1-2. Posterior-inferior myocardial infarction was diagnosed. Emergent coronary angiography (CAG) revealed the wrap-around left anterior descending artery (LAD) with total occlusion distal to the cardiac apex. She underwent percutaneous coronary intervention (PCI). Despite difficulty navigating the long and tortuous LAD, we successfully performed reperfusion of the wrap-around LAD. CAG post-PCI showed the posterior descending artery arising from the LAD, described as hyperdominant LAD.

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.

A 68-year-old man visited our hospital due to anorexia, weight loss and a fever. We diagnosed the patient with disseminated Mycobacterium avium complex (MAC) and confirmed the presence of interferon (IFN)-γ neutralizing autoantibodies (IFN-γAb). His lesions improved following antibiotic therapy, but chylous ascites (CA) developed seven months after treatment. CA was able to be controlled by subcutaneous octreotide and diet therapy. IFN-γAb is recognized as having a critical role in the pathogenesis of disseminated MAC disease, but its clinical features are not fully understood. CA may be a complication that develops during the treatment of disseminated MAC infection.

Molecular-targeted drugs (MTDs), such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase inhibitors, are used to treat non-small-cell lung cancer (NSCLC). The incidence of rash caused by EGFR-TKIs and discontinuation of MTDs because of rash are issues. Rapid desensitization therapy (RDT) was performed in five patients who developed severe rash after introduction of MTDs and was successful in four, all of whom showed no rash relapse. RDT may thus be useful for treating rash in patients receiving MTDs for NSCLC.

An 84-year-old man was admitted with hypoxemia and ground-glass opacities with traction bronchiectasis in both lungs and mild fibrosis on computed tomography. We first suspected that he had acute exacerbation of interstitial pneumonia and initiated methylprednisolone pulse therapy. On day 4, he was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Although the ground-glass opacities were improved with corticosteroid treatment alone, the hypoxemia persisted, and the plasma D-dimer level increased. Anticoagulant therapy was initiated, and the hypoxemia was improved. COVID-19 pneumonia may result in radiological findings similar to those of acute exacerbation of interstitial pneumonia, and corticosteroids and anticoagulant therapy may lead to favorable outcomes.

A 60-year-old woman was admitted to our hospital due to coronavirus disease 2019 (COVID-19) pneumonia with a chief complaint of persistent low-grade fever and dry cough for two weeks. Thoracic computed tomography demonstrated a crazy paving pattern in the bilateral lower lobes. In a COVID-19 ward, we used a novel wireless stethoscope with a telemedicine system and successfully recorded and shared the lung sounds in real-time between the red and green zones. The fine crackles at the posterior right lower lung fields changed from mid-to-late (day 1) to late inspiratory crackles (day 3), which disappeared at day 5 along with an improvement in both the clinical symptoms and thoracic CT findings.

A 70-year-old dextral woman was admitted to a hospital with agraphia for kanji (Japanese morphograms). She had a history of severe constipation, nightmares, and visual hallucinations. Neurological examinations revealed no obvious Parkinson's disease symptoms. She showed poor skills in writing the kanji for looking at picture objects, [e.g., writing the Japanese word "inu" (which means dog) when she saw a drawing of a dog] or dictated words. A reduced striatal uptake of [¹²³I]-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) on single-photon-emission computed tomography and reduced meta-iodobenzylguanidine (MIBG) cardiac uptake on myocardial scintigraphy were detected. The accumulation of amyloid beta in the bilateral cerebral cortices was observed on amyloid-positron emission tomography. We herein report a case of Lewy body dementia with pure agraphia for kanji with underlying Alzheimer's disease pathology.

A 47-year-old woman, who was diagnosed to have systemic lupus erythematosus (SLE), was admitted because she suffered a severe ischemic stroke three weeks after experiencing a transient attack of aphasia. Diffusion-weighted MRI revealed high intensity at the borderzone of the middle cerebral artery (MCA), while the proximal portion of the left MCA was occluded with its vascular wall enhanced by gadolinium. Intravenous methylprednisolone and heparin were administrated without any symptomatic benefit. She developed severe right hemiparesis with aphasia. Isolated cerebral vasculitis in the large vessel has been rarely reported in SLE patients. The presence of an enhanced vascular wall in the MRI with gadolinium could support the diagnosis.

A 38-year-old man presented with primary position upbeat nystagmus accompanied by peripheral neuropathy. The serum vitamin B12 level was low along with high plasma homocysteine level, indicating vitamin B12 deficiency. Cyanocobalamin supplementation showed partial clinical and electrophysiological improvement. Although brain magnetic resonance imaging did not show any abnormal intensity lesions, the electrophysiological findings suggested that a pontomedullary medial lesion was responsible for the upbeat nystagmus. To our knowledge, this is the first case of upbeat nystagmus with low serum vitamin B12. Physicians need to recognize the possibility of vitamin B12 deficiency as a cause of upbeat nystagmus.

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.