Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Methods: Volunteers over 50 years of age underwent radiographic analysis. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis, and sagittal vertical axis (SVA) were measured. The the three Scoliosis Research Society-Schwab sagittal modifiers (PT, SVA, PI–LL) were categorized and the KL grade was assessed. Differences in spinopelvic parameters and Oswestry Disability Index (ODI) scores among KL grades were evaluated. Results: A total of 396 volunteers (160 men, 236 women; mean age, 74.4 years) were analyzed. PI–LL and PT in KL4 were significantly higher compared to that in the other KL grades. However, there were no significant group differences in SVA. In women, but not in men, higher frequencies of the worst modifier grade (++) were observed for PI–LL and PT in the KL3 and KL4 groups compared to those for the other KL grades. In women, the ODI score in KL4 was worse compared to that in the other KL grades. Conclusions Individuals over 50 years of age with severe knee osteoarthritis had poor lumbo-pelvic sagittal alignment. Moreover, the progression severity of knee osteoarthritis had more impact onstronger relationship with lumbo-pelvic malalignment and disability-related low back pain in women than in men.

Background/Aims: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. Methods: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. Results: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06–16.2). Conclusions Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Since late 2013 through March 2014, Japan experienced a rapid rise in measles cases. Here, we briefly report on the ongoing situation and share preliminarily findings, concerns and challenges and the public health actions needed over the coming months and years.

Measles is a notifiable disease in Japan based on nationwide case-based surveillance legally requiring physicians to report all clinically diagnosed and laboratory-confirmed cases within seven days, but preferably within 24 hours. After a large outbreak in 2007–2008 (more than 11 000 cases reported in 2008 alone) and a goal of elimination by April 2015, a catch-up programme using the bivalent measles-rubella (MR) vaccine was offered for grades seven and 12 (ages 12–13 and 17–18 years) from April 2008 through March 2013. During this period, there was an estimated 97% decline in measles notifications, and the cumulative number of reported cases has been steadily declining over the last five years (732 cases in 2009, 447 cases in 2010, 439 cases in 2011, 293 cases in 2012 and 232 cases in 2013). However, since late 2013 through March 2014, the country experienced a resurgence only a year after a large rubella outbreak.

INTRODUCTION: The pathophysiology and mechanism of in-stent restenosis (ISR) after implantation of second-generation drug-eluting stents (DESs) are not fully clear. We compared the morphological characteristics of ISR between first- and second-generation DESs using frequency domain optical coherence tomography (OCT). METHODS: Patients who underwent follow-up coronary angiography (CAG) after first-generation (CYPHER™ and TAXUS™) and second-generation (Nobori®, PROMUS Element™, Resolute Integrity and XIENCE) DES implantations were examined. ISR was defined as lesions of over 50% diameter stenosis at follow-up CAG. Frequency domain OCT was performed at the time of revascularisation of ISR. Tissue morphology was assessed at minimum lumen area. OCT images of DESs at both early (≤ 1 year) and late (> 1 year) phase follow-up were compared. RESULTS: On qualitative OCT assessment, the ratios of homogeneous, layered, heterogeneous without-attenuation and heterogeneous with-attenuation morphologies were 57.1%, 17.1%, 20.0% and 5.7%, respectively, for second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%, respectively, for first-generation DES ISR (n = 36). At late phase follow-up, homogeneous morphology was significantly more common for second-generation DES ISR compared to first-generation DES ISR (first-generation: 8.0% vs. second-generation: 50.0%; p < 0.01) while heterogeneous with-attenuation morphology was significantly more common for first-generation DES ISR (first-generation: 44.0% vs. second-generation: 5.6%; p < 0.01). CONCLUSION Homogeneous tissue morphology was more frequently found for second-generation than first-generation DES ISR, especially in the late phase. This suggested that neointimal hyperplasia was the main mechanism in second-generation DES ISR, and that the neointima was stabilised, much like in bare metal stent implantation.
Aged ; Constriction, Pathologic ; pathology ; Coronary Angiography ; Coronary Restenosis ; diagnostic imaging ; pathology ; Coronary Vessels ; diagnostic imaging ; pathology ; surgery ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Incidence ; Male ; Metals ; Middle Aged ; Neointima ; Retrospective Studies ; Tomography, Optical Coherence

BACKGROUND: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. METHODS: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. RESULTS: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. CONCLUSIONS Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.
Adult ; Aged ; Community Psychiatry ; statistics & numerical data ; trends ; Depression ; epidemiology ; Female ; Health Surveys ; Humans ; Japan ; epidemiology ; Life Style ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Risk Factors ; Socioeconomic Factors