Expanding elderly populations are a major social challenge in advanced countries worldwide and have led to a rapid increase in the number of elderly patients in intensive care units (ICUs). Innovative advances in medical technology have enabled lifesaving of patients in ICUs, but there remain various problems to improve their long‐term prognoses. Post‐intensive care syndrome (PICS) refers to physical, cognition, and mental impairments that occur during ICU stay, after ICU discharge or hospital discharge, as well as the long‐term prognosis of ICU patients. Its concept also applies to pediatric patients (PICS‐p) and the mental status of their family (PICS‐F). Intensive care unit‐acquired weakness, a syndrome characterized by acute symmetrical limb muscle weakness after ICU admission, belongs to physical impairments in three domains of PICS. Prevention of PICS requires performance of the ABCDEFGH bundle, which incorporates the prevention of delirium, early rehabilitation, family intervention, and follow‐up from the time of ICU admission to the time of discharge. Diary, nutrition, nursing care, and environmental management for healing are also important in the prevention of PICS. This review outlines the pathophysiology, prevention, and future directions of PICS.

Introduction We examined the effectiveness of early rehabilitation for the prevention of postintensive care syndrome (PICS), characterised by an impaired physical, cognitive or mental health status, among survivors of critical illness. Methods We performed a systematic literature search of several databases (Medline, Embase and Cochrane Central Register of Controlled Trials) and a manual search to identify randomised controlled trials (RCTs) comparing the effectiveness of early rehabilitation versus no early rehabilitation or standard care for the prevention of PICS. The primary outcomes were short-term physical-related, cognitive-related and mental health-related outcomes assessed during hospitalisation. The secondary outcomes were the standardised, long-term health-related quality of life scores (EuroQol 5 Dimension (EQ5D) and the Medical Outcomes Study 36-Item Short Form Health Survey Physical Function Scale (SF-36 PF)). We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). Results Six RCTs selected from 5105 screened abstracts were included. Early rehabilitation significantly improved short-term physical-related outcomes, as indicated by an increased Medical Research Council scale score (standardised mean difference (SMD): 0.38, 95% CI 0.10 to 0.66, p=0.009) (QoE: low) and a decreased incidence of intensive care unit-acquired weakness (OR 0.42, 95% CI 0.22 to 0.82, p=0.01, QoE: low), compared with standard care or no early rehabilitation. However, the two groups did not differ in terms of cognitive-related delirium-free days (SMD: −0.02, 95% CI −0.23 to 0.20, QoE: low) and the mental health-related Hospital Anxiety and Depression Scale score (OR: 0.79, 95% CI 0.29 to 2.12, QoE: low). Early rehabilitation did not improve the long-term outcomes of PICS as characterised by EQ5D and SF-36 PF. Conclusions Early rehabilitation improved only short-term physical-related outcomes in patients with critical illness. Additional large RCTs are needed.

Heat stroke is a life-threatening injury requiring neurocritical care; however, heat stroke has not been completely examined due to several possible reasons, such as no universally accepted definition or classification, and the occurrence of heat wave victims every few years. Thus, in this review, we elucidate the definition/classification, pathophysiology, and prognostic factors related to heat stroke and also summarize the results of current studies regarding the management of heat stroke, including the use of intravascular balloon catheter system, blood purification therapy, continuous electroencephalogram monitoring, and anticoagulation therapy. Two systems for the definition/classification of heat stroke are available, namely Bouchama’s definition and the Japanese Association for Acute Medicine criteria. According to the detailed analysis of risk factors, prevention strategies for heat stroke, such as air conditioner use, are important. Moreover, hematological, cardiovascular, neurological, and renal dysfunctions on admission are associated with high mortality, which thus represent the potential targets for intensive and specific therapies for patients with heat stroke. No prospective, comparable study has confirmed the efficacy of intravascular cooling devices, anticoagulation, or blood purification in heat stroke. The effectiveness of cooling devices, drugs, and therapies in heat stroke remains inconclusive. Further large studies are required to continue to evaluate these treatment strategies.

T cells must migrate in order to encounter antigen-presenting cells (APCs) and to execute their varied functions in immune defense and inflammation. ATP release and autocrine signaling through purinergic receptors contribute to T cell activation at the immune synapse that T cells form with APCs. Here, we show that T cells also require ATP release and purinergic signaling for their migration to APCs. We found that the chemokine stromal-derived factor-1α (SDF-1α) triggered mitochondrial ATP production, rapid bursts of ATP release, and increased migration of primary human CD4⁺ T cells. This process depended on pannexin-1 ATP release channels and autocrine stimulation of P2X4 receptors. SDF-1α stimulation caused localized accumulation of mitochondria with P2X4 receptors near the front of cells, resulting in a feed-forward signaling mechanism that promotes cellular Ca²⁺ influx and sustains mitochondrial ATP synthesis at levels needed for pseudopod protrusion, T cell polarization, and cell migration. Inhibition of P2X4 receptors blocked the activation and migration of T cells in vitro. In a mouse lung transplant model, P2X4 receptor antagonist treatment prevented the recruitment of T cells into allograft tissue and the rejection of lung transplants. Our findings suggest that P2X4 receptors are therapeutic targets for immunomodulation in transplantation and inflammatory diseases.

Introduction: Our aim in this study was to assess whether the new Glasgow Coma Scale, Age, and Systolic Blood Pressure (GAP) scoring system, which is a modification of the Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP) scoring system, better predicts in-hospital mortality and can be applied more easily than previous trauma scores among trauma patients in the emergency department (ED). Methods: This multicenter, prospective, observational study was conducted to analyze readily available variables in the ED, which are associated with mortality rates among trauma patients. The data used in this study were derived from the Japan Trauma Data Bank (JTDB), which consists of 114 major emergency hospitals in Japan. A total of 35,732 trauma patients in the JTDB from 2004 to 2009 who were 15 years of age or older were eligible for inclusion in the study. Of these patients, 27,154 (76%) with complete sets of important data (patient age, Glasgow Coma Scale (GCS) score, systolic blood pressure (SBP), respiratory rate and Injury Severity Score (ISS)) were included in our analysis. We calculated weight for the predictors of the GAP scores on the basis of the records of 13,463 trauma patients in a derivation data set determined by using logistic regression. Scores derived from four existing scoring systems (Revised Trauma Score, Triage Revised Trauma Score, Trauma and Injury Severity Score and MGAP score) were calibrated using logistic regression models that fit in the derivation set. The GAP scoring system was compared to the calibrated scoring systems with data from a total of 13,691 patients in a validation data set using c-statistics and reclassification tables with three defined risk groups based on a previous publication: low risk (mortality < 5%), intermediate risk, and high risk (mortality > 50%). Results: Calculated GAP scores involved GCS score (from three to fifteen points), patient age < 60 years (three points) and SBP (> 120 mmHg, six points; 60 to 120 mmHg, four points). The c-statistics for the GAP scores (0.933 for long-term mortality and 0.965 for short-term mortality) were better than or comparable to the trauma scores calculated using other scales. Compared with existing instruments, our reclassification tables show that the GAP scoring system reclassified all patients except one in the correct direction. In most cases, the observed incidence of death in patients who were reclassified matched what would have been predicted by the GAP scoring system. Conclusions: The GAP scoring system can predict in-hospital mortality more accurately than the previously developed trauma scoring systems.

Early and accurate diagnosis of sepsis is challenging. Although procalcitonin and presepsin have been identified as potential biomarkers to differentiate between sepsis and other non-infectious causes of systemic inflammation, the diagnostic accuracy of these biomarkers remains controversial. Herein, we performed a comprehensive meta-analysis to assess the overall diagnostic value of procalcitonin and presepsin for the diagnosis of sepsis. We searched three electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for relevant studies. Two authors independently screened articles on the basis of inclusion and exclusion criteria. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. The quality of evidence for diagnostic accuracy in absolute effects, i.e., the number of true or false positives and true or false negatives, gave a particular pre-test probability. We included 19 studies (19 observational studies and no randomized controlled trials) that had enrolled 3012 patients. Analyses of summary receiver operating characteristic curves revealed areas under the receiver operating characteristic curves of 0.84 for procalcitonin and 0.87 for presepsin. The pooled sensitivities and specificities were 0.80 (95% confidence interval 0.75 to 0.84) and 0.75 (95% confidence interval 0.67 to 0.81) for procalcitonin. For presepsin, these values were 0.84 (95% confidence interval 0.80 to 0.88) and 0.73 (95% confidence interval 0.61 to 0.82), respectively. There were no statistically significant differences in both pooled sensitivities (p = 0.48) and specificities (p = 0.57) between procalcitonin and presepsin. Our meta-analysis provided evidence that the diagnostic accuracy of procalcitonin and presepsin in detecting infection was similar and that both are useful for early diagnosis of sepsis and subsequent reduction of mortality in critically ill adult patients. The study was registered in PROSPERO under the registration number CRD42016035784 .