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Circulating growth differentiation factor 15 (GDF-15) increases in response to inflammation and tissue damage. Its association with functional prognosis in cerebral infarction and subarachnoid hemorrhage is established; however, its role in traumatic brain injury (TBI) and its relationship with Sequential Organ Failure Assessment (SOFA) score, an indicator of systemic organ damage in TBI, remains unclear. This study aimed to explore the correlation between GDF-15 and functional outcomes at discharge in patients with TBI and stroke, including its association with SOFA scores in TBI. Patients with cerebral infarction, subarachnoid hemorrhage, and TBI transported within 24 h from July 2020 to August 2022 were included. Multivariable logistic regression analyzed the relationship between GDF-15 levels at admission and functional outcomes at discharge, with age and sex as covariates. Additionally, correlations between GDF-15 levels and SOFA scores were assessed. Multivariable logistic regression showed a relationship between GDF-15 levels at admission and functional outcomes at discharge in cerebral infarction and subarachnoid hemorrhage but not in TBI. In TBI cases, GDF-15 correlated with SOFA scores, indicating its potential as a TBI severity marker. Although functional prognosis at discharge was evaluated, long-term outcomes were not clear, and this will be addressed in future research.

Record-breaking heat waves over the past 20 years have led to a global increase in heat-related deaths, including heatstroke. Heat-related illnesses occur when the body cannot adapt to the elevated temperatures in the environment, leading to various symptoms. In severe situations, such as heatstroke, the body temperature can rise above 40°C, leading to significant injury to body systems, with particular susceptibility of the central nervous system (CNS). Neuroimaging studies conducted months or years after a heatstroke have revealed cellular damage in the cerebellum and other brain regions, including the hippocampus, midbrain, and thalamus, with the potential for long-term neurological complications in survivors of a heatstroke. This mini review aimed to describe the mechanisms and pathways underlying the development of brain injury induced by heatstroke and identify diagnostic imaging tools and biomarkers for injury to the CNS due to a heatstroke.

Traumatic brain injury (TBI) can alter various immune functions, including immunosuppression, and constitutes a risk factor for nosocomial infections and organ dysfunction. Although TBI can induce a decline in immune cell function, the detailed mechanisms remains to be elucidated. We aim to explore transcriptional signatures associated with post-TBI immune alterations in a pilot cohort using a comprehensive transcriptome analysis of immune cells. Three patients with traumatic brain injury and acute subdural hematoma were admitted to our hospital. We focused on three major subsets of immune cells responsible for the immune response: CD4 + T cells, CD8 + T cells, and monocytes. We evaluated the changes in immune function after injury using comprehensive transcriptome analysis. Blood samples were collected immediately after admission and one week later, and the data were compared with those of healthy volunteers. CD4 + , CD8 + T cells, and monocytes, the expression of pathways involved in cellular metabolism—including oxidative phosphorylation, mTORC1 signaling, MYC targets V1 and V2, and the unfolded protein response—was downregulated on day 7 compared with day 1. These findings suggest a transition from marked immune activation and metabolic upregulation on day 1 to an attenuated immune response by day 7. In CD4 + T cells, pathways associated with tissue remodeling and repair, such as hedgehog signaling and epithelial–mesenchymal transition, were upregulated from days 1 to 7, indicating a shift from inflammatory responses toward inflammation resolution and tissue repair. In this pilot study, comprehensive transcriptome profiling suggests time-dependent transcriptional shifts in CD4⁺ T cells, CD8⁺ T cells, and monocytes after TBI. These findings should be interpreted as hypothesis-generating and provide a framework for larger, confirmatory studies.

Diversity of the microbiota, which is essential for lower airway homeostasis, is greatly altered in acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is the ultimate protective treatment for the lungs of patients with severe ARDS, but little is known about its effect on the lung microbiota of these patients. To evaluate the effect of ECMO on the lung microbiota of ARDS patients, we performed 16S rRNA and fungal ITS1 profiling and shotgun sequencing on bronchoalveolar lavage fluid (BALF) collected from ARDS patients due to COVID-19. BALF was collected from 13 patients, five of whom underwent ECMO. In all patients, Pseudomonas was the most abundant of the bacteria. The patients with ECMO had more Pseudomonas and more Klebsiella than those without ECMO. The most abundant fungi were unspecified fungi in the patients with ECMO and Emmia lacerata in the patients without ECMO. Alpha diversity of bacteria and fungi did not differ significantly between the two groups. Human betaherpesvirus 5 and human alphaherpesvirus 1 were predominant in all patients, with human betaherpesvirus 5 decreasing over time in the ECMO patients. The patients with ARDS due to COVID-19 receiving ECMO had a different lung microbiota than those not receiving ECMO.

The gut is a target organ that functions as the “motor” of critical illness. In patients with critical illness, the disrupted gut microbiota following infection and injury could cause diarrhea, pneumonia, and systemic inflammation. For maintaining the gut microbiota, therapeutic approaches are required to modulate host responses and prevent systemic inflammation. Probiotics and synbiotics could maintain the gut microbiota and decrease not only the incidence of diarrhea but also that of ventilator‐associated pneumonia. The effects of probiotics/synbiotics differ with the type of bacteria and disease severity. Adverse effects of probiotics have been reported; therefore, the selection of safe and effective probiotics/synbiotics is warranted. Refractory diarrhea with prolonged dysbiosis may require a novel intestinal therapy, such as fecal microbiota transplantation, to alleviate gut dysbiosis. After severe injury, such as trauma, operation, burn, infection, shock, and bleeding, systemic inflammation progresses in various organs simultaneously. The gut is considered to have an important role in promoting systemic inflammation through bacterial translocation, intestinal lymphatic mediators, gut immunity, etc.

Background Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS. Methods This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry. Results Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1). Conclusions The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.

Background Shift work is common in healthcare, especially in emergency and intensive care, to maintain the quality of patient care. Night shifts are linked to health risks such as cardiovascular disease, metabolic disorders, and poor mental health. It has been suggested that inflammatory responses due to the disruption of circadian rhythm may contribute to health risks, but the detailed mechanisms remain unclear. This study aimed to analyze changes in gene expression in whole blood of healthcare workers before and after a night shift and investigate the molecular pathogenesis of these changes and their impact on health. Methods This was a single-center, prospective, observational study of four medical doctors working night shifts in the emergency department. Blood samples from the subjects were collected before and after the night shift, and RNA sequencing was performed to analyze changes in gene expression in whole blood. The data obtained were analyzed via Ingenuity Pathway Analysis (IPA) core analysis that included canonical pathway analysis, upstream regulator analysis, and functional network analysis. RNA bulk deconvolution was performed to estimate the relative abundance of immune cells. The IPA analysis match feature was also used to assess similarities of gene expression patterns with other diseases. Results We identified 302 upregulated and 78 downregulated genes ( p  < 0.05, |log2-fold change|> 0.5) as genes whose expression changed after the night shift. Canonical pathway analysis revealed that Toll-like receptors and other innate immune response pathways were activated. Upstream regulator analysis and functional network analysis also consistently indicated a predicted activation of innate immune and inflammatory responses. RNA bulk deconvolution showed changes in the proportions of several immune cells. IPA analysis match indicated that gene expression patterns after night shifts were highly correlated with several diseases, including major depressive disorder, in terms of immune and inflammatory responses. Conclusion The results revealed that innate immune and inflammatory responses are elicited after night shifts in healthcare workers and that gene expression patterns correlate with several diseases in terms of immune and inflammatory responses. These findings suggest that shift work may affect health risks through innate immune and inflammatory responses.

Therapeutic hypothermia inhibits organ damage by suppressing metabolism, which makes it a therapy of choice for treating various diseases. Specifically, it is often used to treat conditions involving central nervous system disorders where it is expected to positively impact functional prognosis. Although keeping the body temperature at a hypothermic level has been conventionally used, how to manage the body temperature correctly remains a topic of debate. Recently, the concept of temperature management has been proposed to improve the quality of body temperature control and avoid hyperthermia. This review focuses on the effect of temperature on the central nervous system in conditions involving central nervous system disorders and the practice of temperature management in clinical situations.

Objectives This study aimed to comprehensively compare host responses of patients with bacterial sepsis and those with viral (COVID-19) sepsis by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms. Design Prospective observational study. Setting Whole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having bacterial sepsis or viral (COVID-19) sepsis at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine. Patients Twenty-two bacterial sepsis patients, 35 viral (COVID-19) sepsis patients, and 15 healthy subjects admitted to the department were included. We diagnosed bacterial sepsis patients according to the sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. Viral (COVID-19) sepsis patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans. Interventions None. Measurements and main results For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in the bacterial sepsis patients. Numbers of genes showing upregulated: downregulated gene expression (false discovery rate < 0.05, |log2 fold change| > 1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in viral (COVID-19) sepsis patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated: downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the bacterial sepsis and viral (COVID-19) sepsis patients. Bacterial sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling. Conclusion Our study illuminated distinct molecular variances between bacterial sepsis and viral (COVID-19) sepsis. Bacterial sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to viral (COVID-19) sepsis patients. Especially, bacterial sepsis caused more dramatic pathogenetic changes in the Th1 pathway than did viral (COVID-19) sepsis.

Each patient with a critical illness such as sepsis and severe trauma has a different genetic background, comorbidities, age, and sex. Moreover, pathophysiology changes dynamically over time even in the same patient. Therefore, individualized treatment is necessary to account for heterogeneity in patient backgrounds. Recently, the analysis of comprehensive biomolecular information using clinical specimens has revealed novel molecular pathological classifications called subtypes. In addition, comprehensive biomolecular information using clinical specimens has enabled reverse translational research, which is a data‐driven approach to the identification of drug target molecules. The development of these methods is expected to visualize the heterogeneity of patient backgrounds and lead to personalized therapy. The critically ill patients’ background is heterogeneous and requires individually optimized treatment. Advances in comprehensive biomolecular information measurement and bioinformatics technologies have made it possible to analyze molecular pathogenesis in detail and this enabled reverse translational research for drug discovery.