Objective Conventional risk scores of peptic ulcer disease (PUD) are based on many parameters, and their application in clinical practice is therefore limited. The aim of this study was to establish simple and reliable criteria for predicting PUD-associated mortality.

Methods A total of 499 patients with PUD were divided into 2 groups: the training cohort (n=333) and the validation cohort (n=166). To minimize selection bias due to missing values, we used imputed datasets generated by the multiple imputation method (training-cohort dataset, n=33,300; validation-cohort dataset, n=16,600).

Results In the training-cohort dataset, the heart rate-to-systolic blood pressure ratio (HR/SBP) and serum albumin (s-Alb) level were significant independent predictive factors for mortality according to the multivariate analysis [HR/SBP, odds ratio (OR): 1.72; 95% confidence interval (CI), 1.06-2.80, p=0.028; s-Alb, OR: 0.23, 95% CI, 0.11-0.51, p<0.001]. The model comprising HR/SBP and s-Alb was able to detect mortality due to PUD with an area under the curve (AUC) of 0.855. In the validation-cohort dataset, this model also showed good efficacy with an AUC of 0.835. The novel criteria combining HR/SBP and s-Alb developed by a decision tree analysis showed 73.3% sensitivity and 87.6% specificity for predicting mortality in the total-cohort dataset. Our criteria were superior to the Glasgow Blatchford and Rockall scores and similar to the AIMS65 and Progetto Nazionale Emorragia Digestiva scores for predicting mortality.

Conclusion The combination of the HR/SBP ratio and s-Alb level is a good predictor of mortality in patients with PUD.

Objective A pathological acetylcholine (ACh) test was observed at lower ACh doses in females compared with males in European populations. We retrospectively analyzed the sex-related differences in Japanese patients with provoked positive spasm by ACh spasm provocation testing.

Methods We performed the ACh spasm provocation tests in 1,854 patients from Jan 1991 until Mar 2019. 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. Positive spasm was defined as >90% stenosis and usual chest pain or ischemic ECG changes. We compared the clinical characteristics, angiographical findings during ACh testing, and clinical outcomes between female and male patients with and without provoked positive spasm.

Results Positive provoked spasm was diagnosed in 917 patients including 737 (80.4%) males and 180 (19.6%) females. The incidence of provoked positive spasm in females was significantly lower than that in males (33.5% vs. 56.0%, p<0.001). Female patients with provoked positive spasm tended to be older, have less history of smoking, less provoked spasm in the left circumflex artery, or less focal type spasm than male patients with provoked positive spasm. The incidence of ST elevation during ACh testing in male patients was significantly higher than that in female patients, whereas the frequency of ST depression in females was remarkably higher than that in males. The mean maximum used ACh dose for provoked positive spasm on both coronary arteries in female patients was significantly higher than that in male patients. The observed major complications during ACh testing did not differ substantially between the sexes. In addition, the prognosis in females with provoked positive spasm was not different from males.

Conclusion Provoked positive spasm by ACh test was obtained at lower mean maximum ACh doses in males compared with females in Japanese patients.

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors.

Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight.

Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients.

Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP, are frequently administered to diabetic patients, including those with acromegaly. We aimed to determine whether or not the administration of a DPP4i increases GH concentration, especially in patients demonstrating PI-GH during a DPP4i-OGTT, in which a DPP4i was administered immediately before 75-g OGTT.

Methods This prospective cross-sectional study was carried out on acromegalic patients admitted to Hokkaido University hospital between June 2011 and May 2018. The participants underwent both 75-g OGTT and DPP4i-OGTT. For those who underwent surgery, immunohistochemical staining and quantitative polymerase chain reaction (PCR) for the GIP receptor (GIPR) were performed on the resected pituitary adenomas.

Results Twenty-five percent of the participants had PI-GH confirmed (3 of 12 cases). Two of the three participants who demonstrated PI-GH exhibited higher circulating GH concentrations during DPP4i-OGTT than during OGTT. The increase in plasma glucose was reduced during DPP4i-OGTT compared to during 75-g OGTT, suggesting that the increase in GH during DPP4i-OGTT was due not to high glucose concentrations but instead increased GIP caused by the administration of DPP4i. The adenoma from one participant with PI-GH displayed positive immunostaining for GIPR and a higher GIPR messenger ribonucleic acid (mRNA) expression than the others.

Conclusion DPP4i may enhance the GH secretion response during glucose loading, especially in individuals with PI-GH.

Objective Evidence concerning the safety and efficacy of indacaterol maleate in a real-life setting is limited. The objective of this post-marketing surveillance was to evaluate the real-life safety and efficacy of indacaterol maleate in Japanese patients with chronic obstructive pulmonary disease (COPD).

Methods This was a 52-week post-marketing surveillance conducted between April 2012 and December 2018. The safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs). The efficacy endpoints included the physician-reported global evaluation of treatment effectiveness (GETE), change from baseline in the COPD assessment test (CAT) results, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and %FEV₁ following 4, 12, 26, and 52 weeks of indacaterol administration.

Results Of the 1,846 enrolled patients, 1,726 were included in the safety and efficacy analyses. The mean age of the patients was 72.5 years old. Cough, pneumonia and COPD worsening were the most common AEs reported, while pneumonia (1.04%) was the most common SAE, and cough (1.68%) was the most common ADR. GETE showed that 69.70% of patients achieved an excellent/good/moderate response following indacaterol treatment. The CAT score decreased, and lung function parameters (FVC, FEV₁ and %FEV₁) improved across all the COPD stages following treatment with indacaterol.

Conclusion Indacaterol showed a favorable safety and tolerability profile in Japanese patients with COPD without new safety signals observed in real-life settings. These findings demonstrated that indacaterol is an effective maintenance treatment in real-life practice for Japanese patients with COPD.

Objective Computed tomography (CT) can be used for visualizing acute intracerebral hemorrhages (ICHs) as distinct hyperdense areas and cerebral edema as perihematomal low-density areas (LDAs). We observed a perihematomal LDA on CT, which appeared to be part of a hemorrhage on magnetic resonance imaging (MRI) in acute ICH. We named this "CT perihematomal rim" and evaluated its characteristics and clinical significance.

Methods We stratified patients with acute ICH according to the presence or absence of a CT perihematomal rim and then compared their radiologic findings. Logistic regression analyses were performed to assess whether the CT findings can predict the presence of a CT perihematomal rim.

Patients Patients within 24 hours of ICH onset who were admitted between September 1, 2014, and October 31, 2018, were registered.

Results Overall, 139 patients (91 men; mean age, 66 years) were investigated. CT perihematomal rims were observed in 40 patients (29%). ICH volumes on CT were 30% smaller than those on MRI in patients with CT perihematomal rims. On a multivariate analysis, the presence of a CT perihematomal rim was independently associated with the maximum diameter of the perihematomal LDA. According to a receiver operating characteristic analysis, the maximum LDA diameter threshold was 7.5 mm (sensitivity, 85%; specificity, 83%).

Conclusion CT perihematomal rims were observed in 29% of the patients with acute ICH. A perihematomal LDA (>7.5 mm) in acute ICH cases should be considered a CT perihematomal rim. Clinicians should be aware that the ICH volume on CT may be underestimated by 30%.

Objective The Mini-Z 2.0 is a new, simple, and nonproprietary tool for assessing physician well-being and burnout. To date, a non-English version of the Mini-Z 2.0 survey has not been validated. Therefore, we aimed to develop a Japanese version of the Mini-Z 2.0 and to evaluate its validity and reliability using survey data from physicians affiliated with an internal medicine academic society.

Methods The Mini-Z 2.0 survey was translated into Japanese using a forward-backward translation method. The participants belonged to the American College of Physicians' Japan Chapter. The translated version of the Mini-Z 2.0 survey was distributed to participants using an electronic mailing list. Convergent validity was assessed between burnout and other items using Pearson's product-moment statistic. Structural validity was evaluated using an exploratory factor analysis and confirmatory factor analysis, and reliability was assessed using internal consistency.

Results Of the 1,255 physicians and medical residents contacted, 283 responded (22.5%). Burnout was present in 34.6% of the participants, with 48.8% reporting high stress levels. Convergent validity was demonstrated, with satisfactory correlations between burnout and satisfaction, value alignment, work control, and stress. An exploratory factor analysis identified two factors (i.e., Well-Being and Relationships and Work-Related Stressors); however, the three models evaluated using the confirmatory factor analysis revealed a poor fit. Cronbach's alpha for the sample was 0.80.

Conclusion The Japanese version of the Mini-Z 2.0 demonstrated good internal consistency and convergent validity. Despite its inadequate structural validity, it can be used to measure physician well-being and related workplace conditions in Japan.

Systemic steroid is required for the exacerbation of ulcerative colitis (UC), although its administration should be avoided in patients with a low bone mineral density (BMD) exacerbated by side effects of steroids. We herein report the successful induction of remission in an UC case with a low BMD due to Fanconi-Bickel syndrome-or glycogen storage disease type XI-using granulocyte and monocyte adsorptive apheresis (GMA). For a 43-year-old woman with a BMD of 50% the young adult mean, GMA was performed 2 times a week for a total of 10 times. GMA might be a steroid-free treatment option for UC patients with a low BMD.

A 65-year-old woman with a history of treatment for splenic marginal zone B-cell lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma underwent esophagogastroduodenoscopy. A reddish elevated lesion was found in the fundus of the stomach. On image-enhanced endoscopy, several findings, such as glandular structures of varying sizes suggesting well-differentiated adenocarcinoma, pruned blood vessels, and dilated blood vessels in deeper mucosa suggesting MALT lymphoma, were observed. The final pathological diagnosis after surgical resection was collision tumors of well-differentiated adenocarcinoma and MALT lymphoma. The features of both tumors could be observed simultaneously with image-enhanced endoscopy.

The current study evaluated the application of small-bowel capsule endoscopy (SBCE) in SARS-CoV-2-infected patients with suspected small bowel bleeding. We analyzed the clinical characteristics, SBCE procedures, examination results, and treatment for cases of suspected small bowel bleeding in two patients with critical COVID-19. SBCE showed active spotting bleeding in the jejunum and ileum with no identifiable lesions in case 1, while multiple small bowel ulcers were detected in case 2. Two patients had relevant changes in their management plans and received specific treatment based on SBCE findings. In summary, SBCE proved to be a non-invasive diagnostic tool for critical COVID-19 patients with suspected small bowel bleeding.

Acute liver injury (ALI) has been rarely reported as a clinical finding of adult T-cell leukemia/lymphoma (ATLL). A 74-year-old Japanese female patient who was histologically diagnosed as having autoimmune hepatitis (AIH) one year earlier, showed elevations in her aminotransferase and total bilirubin levels, and this was considered to be an exacerbation of AIH. Liver biopsy revealed interface hepatitis. Because atypical lymphocytes and human T-cell leukemia virus 1 immunoglobulin G antibody were positive, the patient was diagnosed to have ATLL. The biopsy revealed CD4+ and CD8+, but not CD20+ lymphocytes. Thus, the ALI in the patient was due to T-cell infiltration into the liver, and not due to an exacerbation of AIH.

A 49-year-old man underwent treatment with glecaprevir plus pibrentasvir (G/P) for chronic hepatitis C infection. Six weeks later, he was admitted to our hospital because of jaundice and fatigue with no accompanying skin rash. A laboratory examination and evaluation of the patient's history resulted in a diagnosis of acute liver injury. Discontinuation of G/P and a rigorous medical protocol, including plasma exchange and hemodiafiltration, successfully mitigated the liver damage. The patient was also found to be allergic to two drugs other than the G/P therapy. In such cases with a history of drug allergy, careful observation may be required to detect serious adverse events.

Fusobacterium necrophorum is a very rare cause of endocarditis. We herein report a case of F. necrophorum endocarditis with liver abscesses in a 51-year-old woman. This is the first reported case of monomicrobial F. necrophorum endocarditis to present in a patient over 50 years old. We also reviewed 10 reported cases, including the present case. Our review indicated that anaerobic bacteria, including Gram-negative anaerobic bacilli such as F. necrophorum, should be considered in the differential diagnosis of infective endocarditis, especially in patients without preexisting organic heart disease.

We encountered a 70-year-old Japanese woman with neurofibromatosis type 1 (NF1) who had a history of pheochromocytoma and concurrently developed adenomatous goiter, primary hyperparathyroidism, and acromegaly. The patient had a somatotroph adenoma of the adenohypophysis that predisposed her to multinodular goiter. Three parathyroid tumors were detected by cervical ultrasonography and cervicothoracic computed tomography. Genetic analyses did not reveal genetic alterations (e.g. loss-of-function mutation) in the causative genes of endocrine tumors, including MEN1, RET, VHL, CDKN1B, and CDKN2C. The NF1 gene could not be analyzed genetically due to the patient's refusal. The pathophysiologic mechanisms of endocrinopathy concurrence in NF1 remain to be elucidated.

Selenium is essential for human health; its deficiency leads to cardiac dysfunction. We herein report a 79-year-old man on peritoneal dialysis who presented with refractory hypotension caused by selenium deficiency. He was admitted to our hospital with bacterial pneumonia and hypotension and abnormal electrocardiogram (ECG) findings. Despite improvement of pneumonia, his hypotension continued, and intravenous noradrenalin could not be discontinued. His serum selenium level was extremely low, and he was started on intravenous selenium. His hypotension and ECG findings gradually improved, and noradrenalin was discontinued. Physicians should consider selenium deficiency when patients on peritoneal dialysis show refractory hypotension.

We experienced a case of the successful treatment of intractable pulmonary aspergillosis with inhaled liposomal amphotericin B (L-AMB) and oral voriconazole (VRCZ). A 52-year-old man was admitted to our hospital with a fever. Chest computed tomography (CT) revealed an infiltrative shadow. Two separate sputum cultures detected Aspergillus niger. Although we treated the patient with single and combined antifungal agents, the infiltrative shadow worsened. After obtaining sufficient informed consent from the patient, we switched him to an inhaled L-AMB. The infiltrative shadow subsequently improved. The patient has remained well for one year without exacerbation. We herein report the usefulness of inhaled L-AMB and oral VRCZ.

We herein report the case of a 54-year-old Japanese man with hepatitis C virus (HCV)-related membranoproliferative glomerulonephritis (MPGN), which developed at the time of relapse of immune thrombocytopenic purpura (ITP) after rituximab therapy. Antiviral therapy for HCV led to the improvement of both MPGN and ITP. Rituximab therapy may have contributed to the exacerbation of HCV infection and induced the development of HCV-related MPGN and the relapse of ITP. Our case suggested that HCV treatment should be prioritized over rituximab therapy for HCV-positive patients with ITP and that antiviral therapy for HCV may be effective for treating ITP itself.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and severe syndrome characterized by rigidity of the limb and truncal muscles, brainstem signs, myoclonus, and hyperekplexia. Iliopsoas hematoma is a serious complication of bleeding disorders that occurs most commonly in patients with hemophilia and also in association with anti-coagulant drug treatment. We herein present a case of PERM complicated with bilateral iliopsoas hematomas. His neurological symptoms improved after immunotherapy, and thereafter the iliopsoas hematomas disappeared. Neurologists should consider iliopsoas hematomas as a serious potential complication of PERM.

A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected of having cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) because of a family history and brain magnetic resonance imaging findings of cerebral white matter hyperintensities. The cysteine-sparing variation p.Val237Met was identified in NOTCH3. An intensive skin biopsy showed negative results (no granular osmiophilic material or positive NOTCH3 immunostaining), suggesting that the patient's definite diagnosis and pathogenicity of p.Val237Met were uncertain. We additionally reviewed previous reports of two Japanese families with p.Val237Met.

Leukoencephalopathy with high-intensity signals in the corticomedullary junction on diffusion-weighted imaging (DWI) is a diagnostic hallmark for neuronal intranuclear inclusion disease (NIID). We herein report a 65-year-old man who developed dementia and was diagnosed with NIID 2 years later. Of note, he had coincidentally undergone brain magnetic resonance imaging 14 and 10 years before the onset of dementia. No abnormalities were discerned on DWI on either of these occasions, but high-intensity signals in the corticomedullary junction on DWI were revealed two years before the clinical onset. The early recognition of this pathognomonic white matter change may facilitate the presymptomatic diagnosis of NIID.

A 54-year-old man suddenly developed impaired consciousness and left hemiplegia due to a right thalamic hematoma. Emergent ventricular drainage for acute hydrocephalus improved the level of consciousness, but macrosquare-wave jerks (MSWJ) consisting of a right-ward intrusive saccade and corrective saccade appeared. The MSWJ disappeared on day 2 when follow-up CT revealed improvement of hydrocephalus. However, on day 36, after ventricular drainage was clamped, the MSWJ reappeared. After ventriculoperitoneal shunt, MSWJ again subsided. In this patient, hydrocephalus may have stretched the superior colliculus, thereby decreasing activity of the fixation neurons and then omnipause neurons, and eventually resulting in the reversible MSWJ.

A 51-year-old man with a history of renal cell carcinoma presented with sudden aphasia, right hemiparesis, and dysesthesia. MRA showed left middle cerebral artery occlusion, and he was diagnosed with acute ischemic stroke and treated with intravenous recombinant tissue plasminogen activator and endovascular thrombectomy. The pathological diagnosis of the retrieved thrombus was consistent with the already-known pathological findings of the primary renal cell carcinoma. Therefore, a diagnosis of cerebral embolism caused by tumor cells was made. The pathological findings of the retrieved thrombi were important in determining the cause of ischemic stroke.

Age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder (LPD) occurs in elderly patients without immunodeficiency. An 81-year-old woman without any known immunodeficiency was examined for fever, rash, arthritis, thrombocytopenia, pleural and pericardial effusions, lymphadenopathy, and positive autoantibodies, which satisfied the classification criteria for systemic lupus erythematosus (SLE). However, a lymph node biopsy revealed EBV-LPD, and she was diagnosed with age-related EBV-LPD. In young individuals, EBV infection is a major differential diagnosis of SLE, but to our knowledge, this is the first reported case of age-related EBV-LPD mimicking SLE. We should therefore consider EBV-related disorders in the differential diagnosis of SLE even in elderly individuals.

Digital clubbing has been regarded as an important sign in medicine. A 33-year-old woman with no history of hepatic, pulmonary, or malignant disease was referred to our hospital. She had been taking lubiprostone every day for three years for constipation. Clubbing in her upper and lower limb digits began gradually about two years ago. The results of laboratory investigations were almost normal. We suspected the clubbed digits were a side effect of lubiprostone and confirmed that the levels of urinary prostaglandin E2 (PGE2), which can cause clubbed digits, were elevated. Thus, we instructed the woman to stop taking lubiprostone and monitored this lab value. However, the value continued to rise over 2 months to 41.9 μg/g Cr. During that time, she had been taking sennoside A B calcium instead of lubiprostone for constipation. Since sennoside A B calcium also has the effect of increasing PGE2, we ordered the discontinuation. Her urinary PGE2 to creatinine level normalized, and the clubbing improved after the discontinuation of these two medications.