せん妄の遷延化に関連する因子についての後方視研究

Background: It has been reported that delirium causes various problems. Many researchers have reported the risk factors associated with the onset of delirium; however, there are few reports focused on persistent delirium. This study aimed to identify the risk factors associated with persistent delirium. Methods: A total of 573 patients hospitalised in Nara Prefecture General Medical Centre from October 2014 through September 2017 who were referred to the psychiatry consultation service were included in this study. Persistent delirium was defined as delirium lasting for 14 days or more. A retrospective study was carried out based on the patients' records. The relationship between various background factors and persistent delirium was statistically analysed. Results: Of the 573 hospitalised patients, 295 were diagnosed as having delirium. Forty-six patients with persistent delirium and 181 patients with nonpersistent delirium were included in this study. Multivariable logistic regression analyses revealed that male gender, opioid analgesics use, non-opioid analgesics use, and low serum sodium were significantly and independently associated with persistent delirium. Ramelteon or trazodone was used significantly more in persistent delirium, although each use was not significant. Conclusion: This is the first study to reveal that male gender and use of analgesics were associated with persistent delirium in general hospital. However, as this is a case-control study and may contain bias, future cohort studies and intervention studies are needed. It is also necessary to investigate the relevance of the 'degree of pain' behind the use of analgesics.博士（医学）・乙第1516号・令和3年12月21日© 2021 Japanese Psychogeriatric Society.This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/psyg.12655], which has been published in final form at [https://doi.org/10.1111/psyg.12655]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

Anti-inflammatory Effect of Ghrelin in Lymphoblastoid Cell Lines From Children With Autism Spectrum Disorder

The gut hormone ghrelin has been implicated in a variety of functional roles in the central nervous system through the brain-gut axis, one of which is an anti-inflammatory effect. An aberrant brain-gut axis producing immune dysfunction has been implicated in the pathobiology of autism spectrum disorder (ASD), and elevated expression of inflammatory markers has been shown in blood and brain tissue from subjects with ASD. We hypothesized that ghrelin may mitigate this effect. Lymphoblastoid cell lines from typically developed children (TD-C) (N = 20) and children with ASD (ASD-C) (N = 20) were cultured with PBS or human ghrelin (0.01 μM) for 24 h, and mRNA expression levels of the inflammation-related molecules interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB) were measured to examine the effects of ghrelin as an anti-inflammatory agent. Expression levels of TNF-α and NF-κB mRNA, but not IL-1β or IL-6, were significantly elevated in ASD-C compared to TD-C. Ghrelin showed a tendency to reduce the expression of TNF-α and NF-κB, but this was not statistically significant. Considering the heterogenous pathobiology of ASD, we examined the effects of ghrelin on TD-C and ASD-C with expression levels of TNF-α and NF-κB in the highest and lowest quartiles. We found that ghrelin markedly reduced mRNA expression of TNF-α and NF-κB s in ASD-C with highest-quartile expression, but there were no effects in ASD-C with lowest-quartile expression, TD-C with highest quartile expression, or TD-C with lowest quartile expression. Together, these findings suggest that ghrelin has potential as a novel therapeutic agent for ASD with inflammation and/or immune dysfunction

精神疾患におけるマイクログリア由来ニューレグリン発現

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.博士（医学）・乙第1404号・平成29年6月28日Copyright © 2017 Elsevier Inc. All rights reserved

NARP-related alterations in the excitatory and inhibitory circuitry of socially isolated mice: developmental insights and implications for autism spectrum disorder

BackgroundSocial isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).MethodsMice were subjected to social isolation during postnatal days 21–35 (P21–P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.ResultsIn adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.ConclusionOur study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Cytomegalovirus Colitis Followed by Colonic Pseudolipomatosis and Gastric Emphysema in a Post-resuscitation Patient

A 64-year-old Japanese man suffered cardiopulmonary arrest, which may have resulted from sepsis and/or hyperosmolar hyperglycemic non-ketonic coma, and was admitted after successful resuscitation. He had watery diarrhea on day 18 and was diagnosed with cytomegalovirus enterocolitis. In addition, computed tomography performed on day 27 and colonoscopy revealed gastric emphysema and intestinal pseudolipomatosis, respectively. This report is the first to describe a patient with cytomegalovirus enterocolitis and subsequent gastric emphysema and pseudolipomatosis. Gastrointestinal cytomegalovirus infection may underlie gastric emphysema and intestinal pseudolipomatosis, particularly in patients with relative or obvious immune dysfunction