Objective It is well known that poor sleep increases the risk of heart failure (HF). However, the underlying mechanisms remain unclear. In this study, we investigated the association of poor sleep with hemodynamic stress on the left ventricle, which was a key factor for the development of HF in elderly individuals.

Methods A total of 2,301 participants (≥65 years old) without cardiac disease were enrolled in this cross-sectional analysis. We evaluated the subjective sleep quality, sleeping difficulty, subjective sleep duration, use of sleeping pills, and daytime dysfunction using the Pittsburgh Sleep Quality Index, a 19-item self-reported questionnaire. We assessed serum N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of hemodynamic stress on the left ventricle, and we defined high NT-proBNP as a serum NT-proBNP level ≥ 125 pg/mL.

Results Sleeping difficulty was significantly associated with high NT-proBNP levels [odds ratio (OR), 1.46; 95% confidence interval (CI), 1.16-1.85; p<0.005]. A subjective short sleep duration was also significantly associated with high NT-proBNP levels (OR, 1.69; 95% CI, 1.03-2.75; p<0.05). A subjective poor sleep quality, the use of sleeping pills, and daytime dysfunction were not associated with serum NT-proBNP levels. All data were adjusted for the age, sex, body mass index, serum hemoglobin concentration, serum creatinine level, systolic blood pressure, diastolic blood pressure, and use of antihypertensive medications.

Conclusion Poor sleep was associated with high hemodynamic stress to the left ventricle in elderly population.

Objective Snoring is a common physical condition in active workers. However, the link between snoring and health problems is poorly understood. Therefore, the prevalence of snoring in Japanese workers and the relationships between snoring and lifestyle-related diseases were investigated.

Methods This was a retrospective, single-center, cross-sectional study. The results of a single year's medical examinations were investigated for 25,141 Japanese active office workers 20 to 59 years old. The presence and duration of snoring were investigated using a personal computer at a medical interview before the medical checkup. The snoring frequency was investigated for each gender. In addition, the relationships between snoring and hypertension, diabetes, and dyslipidemia were also analyzed.

Results Men (21,774) were a mean 46±6 years old with a snoring prevalence of 43%. Women (3,367) were a mean 46±6 years old with a snoring prevalence of 20%. In men, snoring was an independent comorbid factor of hypertension and dyslipidemia. In particular, a long snoring vintage (multiple years) was an independent comorbid factor for hypertension [odds ratio (OR), 1.14; 95% confidence interval (CI), 1.05-1.24; p=0.002; and OR, 1.20; 95% CI, 1.07-1.34; p=0.001]. In women, snoring was not an independent comorbid factor for lifestyle-related diseases when adjusted for the age and body mass index.

Conclusion Snoring was shown to be a frequent pathophysiology in active workers. It was a health indicator for active workers, and especially in men, intervention for snoring may reduce the risk of developing lifestyle-related diseases.

Objective The measurement of C-peptide immunoreactivity (CPR) is essential for evaluating the pancreatic β-cell function and selecting appropriate therapeutic agents in patients with diabetes mellitus. The meal tolerance test (MTT) is simple to administer physiological insulin-stimulating test. Previous studies have reported that several CPR-related indices are useful markers for predicting insulin requirement in type 2 diabetes. In the present study, we investigated the serum CPR response during the MTT in hospitalized patients with type 2 diabetes mellitus in order to clarify the clinical utility of the MTT.

Methods We performed the MTT using a test meal with timed measurements of the serum CPR level based on the oral glucose tolerance test over 180 minutes and tested the correlation of various CPR-related indices and clinical factors in patients with type 2 diabetes mellitus.

Patients The subjects were patients with type 2 diabetes mellitus who had been admitted to our hospital for diabetes management and education. The final study population consisted of 68 patients.

Results The fasting CPR level was correlated with the 24-hour urinary CPR excretion and body mass index. The serum CPR level at 120 minutes in the MTT was strongly correlated with the area under the curve of CPR during the MTT. The patients who needed insulin therapy at 6 months after hospitalization showed a significant lower incremental CPR value from 0 to 120 minutes in the MTT than those who did not need insulin therapy.

Conclusion The plasma C-peptide levels at 0 and 120 minutes in the MTT provide essential information for the clinical management of patients with type 2 diabetes mellitus.

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity.

Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio.

Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m² and whose night-to-day ratio of systolic BP was >0.90, even after adjustment.

Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.

Recently, immune checkpoint inhibitors (iCIs) have been used to treat cancers. Once some of the iCIs for the treatment of hepatocellular carcinoma (HCC) are certified in clinical trials, they are likely be administered to HCC patients with hepatitis C virus (HCV). However, the immunopathogenesis of HCV after the administration of iCIs has not been clarified. We experienced a lung cancer patient with HCV infection treated by nivolumab, programmed cell death 1 (PD-1) antibody. HCV-RNA gradually decreased after the start of nivolumab treatment. However, no increase in transaminase was observed during the decline of HCV-RNA. It was thought that HCV-specific cytotoxic T lymphocytes (CTLs) were activated by iCIs.

Eosinophilic gastroenteritis (EGE)-associated duodenal ulcer is rare and its endoscopic and pathological features remain poorly described. A 15-year-old boy was referred to our hospital for further examination and treatment of duodenal ulcer. Esophagogastroduodenoscopy (EGD) revealed two A2-stage duodenal ulcers on the duodenal bulb. A biopsy revealed marked infiltration of eosinophils, suggestive of EGE-associated duodenal ulcers. Thus, treatment with crushed budesonide (9 mg/day) was started. EGD revealed healing of the duodenal ulcers seven months after treatment. To our knowledge, this is the first report describing EGE-associated duodenal ulcer successfully treated with crushed budesonide.

Methotrexate-related lymphoproliferative disorder (MTX-LPD) is known to be a side effect of MTX, but its involvement in the liver has been rarely reported. We herein report a 70-year-old woman with autoimmune hepatitis and rheumatoid arthritis who developed multiple liver tumors. We initially considered that she had developed rapid-growing hepatocellular carcinoma (HCC) in the cirrhotic liver based on imaging tests. A tumor biopsy and transcatheter arterial chemoembolization were thus performed. The tumors were then diagnosed as diffuse large B-cell lymphoma pathologically and considered to be MTX-LPD. This case indicates that MTX-LPD should be considered even in cirrhotic patients with liver tumors resembling HCC.

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

A 59-year-old man with type 1 diabetes presented with heart failure. Echocardiography showed large vegetations on the mitral and aortic valves. Blood bacterial culture was positive for Staphylococcus warneri, a coagulase-negative staphylococcus (CoNS) family member. He was diagnosed with native valve endocarditis (NVE) induced by the resident bacteria and ultimately underwent double valve replacement. Retrospectively, slight laboratory data abnormalities and weight loss beginning four months before may have been signs of NVE. He had no history of immunosuppressive therapies or medical device implantation. Thus, CoNS can cause NVE after a long asymptomatic course in patients with poorly controlled diabetes.

We herein report a woman diagnosed with cardiac sarcoidosis (CS) based on the presence of epithelioid granulomas in non-cardiac organs and clinical findings including sustained ventricular tachycardia (VT) and cardiac dysfunction. She stopped oral corticosteroid after 4 years of treatment, and an abnormal myocardial uptake of fluorine-18 fluorodeoxyglucose and sustained VT recurred 3.5 years later. There is no consensus concerning whether or not corticosteroid therapy should be discontinued in the treatment of CS. As a relapse of sarcoidosis-related inflammation may be associated with life-threatening arrhythmia, some patients should continue corticosteroid therapy, even at low doses.

A 79-year-old man without a history of diabetes underwent orchiectomy for prostate cancer. Eight months after the operation, he suffered severe deterioration of visceral fat deposition, fatty liver and diabetes. Treatment for diabetes with canagliflozin and dulaglutide resulted in improvement in his glycemic control, visceral fat and fatty liver. Visceral fat-dominant deposition, which differs from the typical course after androgen deprivation therapy, may have been associated with severe exacerbation of diabetes and fatty liver. Glycemic management with a sodium glucose cotransporter 2 (SGLT2) inhibitor and glucagon-like peptide (GLP)-1 receptor agonist may help improve the glucose metabolism, visceral fat deposition and fatty liver after orchiectomy.

The Gram-negative diplococcus Neisseria macacae is a commensal bacterium of the mucosal surfaces in humans. A 52-year-old woman receiving continuous ambulatory peritoneal dialysis was admitted because of abdominal pain and turbid peritoneal fluid. N. macacae was isolated from peritoneal fluid culture and showed susceptibility to ceftriaxone. Despite appropriate antibiotics, the peritonitis was refractory, leading to the removal of the peritoneal dialysis catheter. We herein report the first case of peritoneal dialysis peritonitis caused by Neisseria macacae and review previous case reports of N. macacae infection in humans.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology and is pathologically characterized by non-caseating granulomas in the organs involved. We herein report a case of sarcoidosis in a Japanese woman with acute respiratory failure, diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on the ventilator after intubation. Only a few cases of previously undiagnosed sarcoidosis presenting acute respiratory failure have been reported. It is important to be aware that undiagnosed sarcoidosis may present with acute respiratory failure. Therefore, EBUS-TBNA under mechanical ventilation may be useful for the immediate diagnosis of patients.

We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.

We herein report a 50-year-old man with alcoholic cirrhosis who developed loss of consciousness and tremor of the upper limbs. Magnetic resonance imaging findings were suggestive of limbic encephalitis with bilateral hippocampal damage, and a cerebrospinal fluid (CSF) examination confirmed anti-N-methyl-D-aspartate (NMDA) and anti-glutamate receptor antibodies. Despite initial corticosteroid therapy, meningeal irritation symptoms appeared, owing to the development of cryptococcal meningitis (CM), diagnosed by the detection of cryptococcal capsular polysaccharide antigen in the follow-up CSF analysis. Cerebral infarction with reversible stenosis of major cerebral arteries during the clinical course was also observed. Following administration of antifungals and corticosteroids, the number of cells in the CSF gradually declined, and NMDA receptor antibodies disappeared. Our study demonstrates the unique coexistence of CM with anti-NMDA receptor encephalitis in adults.

A 61-year-old Japanese man presented with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. NR1 antibodies were detected in his cerebrospinal fluid. Chest computed tomography revealed lung tumor. The patient was diagnosed with paraneoplastic anti-NMDAR encephalitis associated with lung cancer and treated with two cycles of intravenous high-dose methylprednisolone and one cycle of intravenous immunoglobulin. However, he died one year later without improvement. An autopsy confirmed small-cell lung cancer (SCLC). Immunohistochemistry revealed the expression of NR1 subunits in the tumor cells, suggesting that SCLC may trigger NR1 autoimmunity though the expression of NR1 subunits as onconeural antigens, expanding the phenotypic spectrum of paraneoplastic neurological syndrome associated with SCLC.

Spastic paraplegia type 4 (SPG4) is caused by mutations of the SPAST gene and is the most common form of autosomal-dominantly inherited pure hereditary spastic paraplegia (HSP). We herein report a Japanese patient with SPG4 with a confirmed de novo mutation of SPAST. On exome sequencing and Sanger sequencing, we identified the heterozygous missense mutation p.R460L in the SPAST gene. This mutation was absent in the parents, and the paternity and maternity of the parents were both confirmed. The patient showed a pure SPG4 phenotype with an infantile onset. This study may expand the clinical and genetic findings for SPG4.

Infectious disease with various presentations in systemic lupus erythematosus often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic synovitis with epithelioid granuloma. A mycobacterial culture confirmed invasive mycobacterial tenosynovitis due to Mycobacterium chelonae. The patient was treated with moxifloxacin and clarithromycin and completely recovered.

A 50-year-old woman presented with coma and hemorrhagic shock. A rapid influenza antigen test revealed influenza A infection; other laboratory examinations ruled out any other suspected infections. She was diagnosed with hemorrhagic shock and encephalopathy syndrome (HSES) induced by influenza A. She was administered methylprednisolone pulse therapy and peramivir. Subsequently, she was discharged without any sequelae. Only a few cases of influenza-induced HSES have been reported, and the clinical outcomes were very poor. We herein report a successfully treated adult case of influenza-induced HSES and review this rare syndrome.

A 42-year-old man exhibiting hypoxia was diagnosed with coronavirus disease 2019. He had medical histories of type 2 diabetes, hyperlipidemia, hyperuricemia, and gout attack. He received favipiravir for compassionate use for 14 days. Subsequently, he showed increased uric acid levels and developed acute gouty arthritis. Favipiravir may induce not only hyperuricemia but also acute gouty arthritis. It should therefore be used with caution in patients with a history of gout and those with hyperuricemia, especially when used at a higher dose and for a longer duration than is typical.