SHOCK最新文献

{"title":"Pancreatic Stone Protein in Co-Evaluation with qSOFA and NEWS2 for Early Sepsis Detection at the Emergency Department.","authors":"Asimina Safarika, Georgia Damoraki, Konstantinos Katsaros, Soraya Hannane, Iwan Märki, Hiroaki Tanaka, George Giannikopoulos, Evangelos J Giamarellos-Bourboulis","doi":"10.1097/SHK.0000000000002720","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002720","url":null,"abstract":"<p><strong>Background: </strong>Prompt sepsis identification at emergency department (ED) triage is essential for timely treatment and improved outcomes. This study evaluated the diagnostic performance of pancreatic stone protein (PSP) in combination with the quick Sequential Organ Failure Assessment (qSOFA), and the National Early Warning Score (NEWS2) for early sepsis detection.</p><p><strong>Methods: </strong>As part of the PROMPT study - a non-interventional, multicenter trial across six Greek hospitals - blood samples were collected within the first hour of ED admission. PSP levels were retrospectively assessed using nanofluidic near-patient immunoassay device (abioSCOPE, Abionic SA, Switzerland) in 362 adult patients with suspected infections and evaluated their qSOFA and NEWS2 scores. Objectives included evaluating qSOFA's performance, assessing the performance of PSP to identify high-risk patients with qSOFA ≤1, and determining the added value of combining PSP with qSOFA or NEWS2 (cut-off ≥7), using standard performance metrics.</p><p><strong>Results: </strong>Among 156 sepsis cases, 128 (82.1%) had qSOFA scores ≤1. A qSOFA score ≥2 demonstrated a sensitivity of 17.9% and a specificity of 97.1%. In comparison, a qSOFA score of 1 showed a sensitivity of 44.2% and a specificity of 63.6%, while a score of 0 yielded a sensitivity of 37.8% and a specificity of 39.3%.The addition of PSP (cut-off: 300 ng/mL) to qSOFA ≤1 improved specificity to 94.0%, with a sensitivity of 14.8%-closely mirroring the performance of qSOFA ≥2. Similarly, combining PSP with NEWS2 <7 increased true positive cases from 34 to 52, enhancing sensitivity while maintaining high specificity.</p><p><strong>Conclusion: </strong>This study highlights the utility of combining PSP level in the patient's blood with existing scoring systems to enhance early sepsis detection in high-risk ED patients. Future research will explore near-patient PSP measurements at ED triage to further refine and expedite sepsis management.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic assessment of low versus high volume resuscitation in a combined porcine model of severe burn and traumatic brain injury.","authors":"Linda M Schutzman, Sandra L Taylor, Oliver Fiehn, Timothy M Guenther, Marguerite W Spruce, Lindsay M Bach, Connor M Caples, Carl A Beyer, John K Grayson, Jeffrey R Fine, Frederick J Meyers, Tina L Palmieri, Ian E Brown","doi":"10.1097/SHK.0000000000002719","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002719","url":null,"abstract":"<p><strong>Background: </strong>Severe burns continue to be associated with significant morbidity and mortality despite advances in resuscitation techniques. Concomitant injury such as traumatic brain injury adds complexity to resuscitation paradigms as high volume fluid resuscitation together with high losses of plasma proteins may lead to poor outcomes with respect to traumatic brain injury and associated cerebral edema. Currently, \"goal-directed\" methods of resuscitation are utilized in which clinical end points guide fluid volume needs. Unfortunately, clinical changes often indicate that significant organ dysfunction has already occurred. In this targeted metabolomics study, we compare \"aggressive\" versus \"restrictive\" fluid resuscitation strategies to identify compounds indicative of injury progression.</p><p><strong>Methods: </strong>A porcine model of combined brain injury and severe burns was utilized. Injured animals were randomized to receive either \"aggressive\" fluid resuscitation using the Parkland formula or \"restrictive\" resuscitation with the modified Brooke formula. Resuscitation was continued for 8 hours. Plasma and urine samples were collected for targeted analysis of oxylipins and steroids by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).</p><p><strong>Results: </strong>Sixty-nine serum and urinary oxylipins were identified. Significant elevations of 15 urinary oxylipins were noted in animals who received the restrictive resuscitation strategy. No significant differences in plasma oxylipins were found. Twenty-eight serum steroids and 29 urinary steroids were isolated. The concentrations of 3 serum steroids were significantly higher the \"restricted\" resuscitation group. No differences in urinary steroids were identified.</p><p><strong>Conclusions: </strong>In this study, targeted metabolomics was used to identify plasma and urinary oxylipins and steroids in both the restrictive and aggressive resuscitation groups. Notably, significant elevations in 15 urinary oxylipins and 3 serum steroids were identified only in animals that were randomized to \"restricted\" resuscitation. These findings demonstrate detectable differences in lipid metabolites within 8 hours of severe injury, which may correlate with differences in inflammation and facilitate goal-directed resuscitation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarker and Raman analysis of leukocytes in the multicenter INTELLIGENCE trials: at the Intensive Care Unit (INTELLIGENCE-1) and the Emergency Department (INTELLIGENCE-2).","authors":"Evangelos J Giamarellos-Bourboulis, Daniel Thomas-Rüddel, Aikaterini Pistiki, Anuradha Ramoji, Oleg Ryabchykov, Kazi Sultana Farhana Azam, Konstantinos Toutouzas, Athanasios Prekates, Stylianos Karatzas, Christos Mathas, Antigone Kotsaki, Stamatios Chalvatzis, Nikolaos Antonakos, Georgia Damoraki, Jan Rüger, Florian Knorr, Natalie Arend, Anja Silge, Iwan Schie, Jesper Eugen-Olsen, Thomas Bocklitz, Michael Bauer, Johannes Winning, Michael Kiehntopf, Jürgen Popp, Frank Bloos, Ute Neugebauer","doi":"10.1097/SHK.0000000000002699","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002699","url":null,"abstract":"<p><strong>Background: </strong>Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, goes along with a complex and not yet fully understood host response. Despite many different biomarkers, optimal screening tools to identify patients with sepsis are still needed. In a previous, single-center clinical trial with well-defined and well-separated patient cohorts, a new biophotonic marker based on the Raman spectroscopic characterization of leukocytes showed added value to stratify patients and identify infection and sepsis.</p><p><strong>Results: </strong>In the INTELLIGENCE studies, 279 patients from six centres in two countries were analysed and the Raman spectra of ~1500 leukocytes per patient measured within only 1 hour. This marks a huge step from bench to bedside regarding usability and technology readiness level of Raman spectroscopy in multicentre clinical trials. With a discriminatory power comparable to individual conventional biomarkers (CRP, PCT, IL-6, suPAR), the Raman score of leukocytes could not provide added value to the clinical discrimination of sepsis in the INTELLIGENCE-1 study cohorts of intensive care patients with infections. When translating the classification model from INTELLIGENCE-1 to the heterogeneous patient cohort recruited at the emergency department of the double-blinded INTELLIGENCE-2 trial, the Raman score failed to provide added value.</p><p><strong>Conclusions: </strong>In theory, Raman assessment of leukocytes might still be a promising tool for sepsis diagnosis and patient stratification, but there is more basic, translational and clinical research needed to refine its usability and clinical role, probably also taking questions of the pathophysiology of the dysregulated host response for a phenotype stratification into account.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutritional status-based model for predicting low-lactate shock: A retrospective cohort study.","authors":"Xiaofang Xu, Fang Hu, Zhaocai Zhang","doi":"10.1097/SHK.0000000000002710","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002710","url":null,"abstract":"<p><strong>Background: </strong>Although Sepsis-3.0 defines septic shock as hypotension with serum lactate levels >2.0 mmol/L, this criterion may miss low-lactate shock: a clinically significant phenotype characterized by hypotension but without elevated lactate levels. The epidemiological characteristics and prognostic significance of low-lactate shock remain unclear, highlighting a critical gap in current shock management models.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 3,134 patients with shock admitted to a tertiary care medical institution from January 2015 to March 2022. We used propensity score matching (1:2 ratio) to control for confounding factors, aiming to determine the prevalence of low-lactate shock (lactate ≤ 2.0 mmol/L), identify risk factors through multivariable logistic regression, and validate the predictive model (NRS-APACHE II-TG-TBIL) using ROC analysis.</p><p><strong>Results: </strong>The 28-day mortality rate was slightly lower in the low-lactate shock group compared to the high-lactate group (25.4% [94/369] vs. 35.8% [990/2,765], respectively). The age, nutritional risk screening (NRS-2002) score, and venous thromboembolism (VTE) risk score were significantly lower in the low-lactate shock group than in the high-lactate shock group (P < 0.05). No statistically significant differences were observed in gender distribution (P = 0.092). Multivariable analysis identified four independent predictors of low-lactate shock: NRS-2002 (OR=0.570, P<0.001), APACHE II (OR=0.869, P<0.001), TG (OR=0.772, P=0.035), and TBIL (OR=0.993, P=0.002). The composite NRS-APACHE II-TG-TBIL model showed excellent discrimination (AUC=0.800, P<0.001) with balanced sensitivity (72.6%) and specificity (73.5%).</p><p><strong>Conclusions: </strong>Low-lactate shock carries substantial mortality risk (25.4%). The validated NRS-APACHE II-TG-TBIL model (AUC=0.800) provides an effective tool for early detection, addressing critical diagnostic gaps in shock management.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.","authors":"Yipeng Fang, Aizhen Dou, Yunfei Zhang, Ying Zhang, Ying Gao, Keliang Xie","doi":"10.1097/SHK.0000000000002714","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002714","url":null,"abstract":"<p><strong>Background: </strong>Metabolic reprogramming has emerged as a central mechanism in sepsis pathogenesis, influencing immune responses, organ dysfunction, and therapeutic outcomes. This study conducts a comprehensive bibliometric analysis to map the research landscape, identify key trends, and highlight future directions in this field.</p><p><strong>Methods: </strong>Based on the Science Citation Index Expanded database in Web of Science Core Collection (WOSCC) database, we retrieved and analyzed 672 English-language original research articles and reviews. Using R-bibliometrix, VOSviewer, and CiteSpace we performed a multidimensional analysis of academic output trends, geographical distribution, institutional and author collaboration networks, burst detection and the evolution of research hotspots.</p><p><strong>Results: </strong>The analysis reveals a consistent upward trend in both publication output and citation frequency within this research domain. The United States (24.3% of total publications) and China (23.4%) have emerged as the most productive contributing nations. Notably, the United States maintains superior academic influence as evidenced by its highest citation frequency. Among institutions, Wake Forest University in the United States holds a preeminent position, having published 54 high-impact articles in this field. The journals Frontiers in Immunology, Shock, and Critical Care, represent the premier academic platforms in this research domain. Immunometabolism, mitochondrial regulation, gut microbiota imbalance, epigenetic modifications, along with the mTOR/AMPK/HIF-1α axis and the Sirtuin family pathway has been identified as the key research hotspots. Novel therapeutic approaches targeting metabolic regulation are rapidly emerging, including pharmacological agents, natural compounds, stem cell-based therapies, and non-coding RNA interventions.</p><p><strong>Conclusion: </strong>Research on metabolic reprogramming in sepsis shows promising prospects, with investigations into key mechanisms focusing on current research hotspots and the development of metabolism-targeted interventions emerging as critical priorities for future sepsis prevention and treatment strategies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Multi-organ Dysfunction After Trauma with Secondary Sepsis in Rats: A 6-72 hours Temporal Map Validated by Rodent-Specific MODS Scoring.","authors":"Baisheng Sun, Dongxu Qian, Cong Zhang, Ziwei Han, Zhi Mao, Feihu Zhou","doi":"10.1097/SHK.0000000000002704","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002704","url":null,"abstract":"<p><strong>Purpose: </strong>To quantify the temporal evolution of multi-organ dysfunction syndrome (MODS) following trauma with secondary sepsis and to validate a rodent-specific MODS scoring system over 6-72 hours.</p><p><strong>Methods: </strong>A total of 168 male Sprague-Dawley rats (8 weeks old, SPF grade) were randomly divided into four groups: the normal control group (NC group), limb crush injury group (Fx group), cecal ligation and perforation group (CLP group), and limb crush injury combined with CLP group (Fx+CLP group). A stepwise CLP surgery was performed in the Fx+CLP group 24 hours after closed tibial and fibular fracture surgery to mimic the clinical window of high infection incidence. Five observation time points were set: 6, 12, 24, 48, and 72 hours. Hematological parameters were detected and tissues of rats were examined histopathologically before a diagnostic scoring system for MODS in experimental animals was constructed.</p><p><strong>Results: </strong>The mortality rate of the Fx+CLP group was 58.33%, significantly higher than in the other groups (P<0.01). The levels of white blood cell (WBC), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the Fx+CLP group, which peaked at 24 hours, were notably higher than those of the CLP group at each time point (P<0.01). During the organ-function-assessment, the Fx+CLP group started to present with cardiac and hepatic dysfunction 12 hours after the 1st onset, and pulmonary and renal dysfunction 24 hours after the 1st onset. The pathological damage to the organs worsened with time. Particularly, the brain tissue pathology suggested that the pathological score of the Fx+CLP group exceeded 2 at 24 hours after the 1st onset. Moreover, coagulation dysfunction started 12 hours after the 1st onset. In general, the timing features of organ damage were distinct, and the overall damage was much more severe than in the single-factor damage groups.</p><p><strong>Conclusions: </strong>A consecutive 6-to-72-hour quantitative profile of MODS across six organ systems was established, demonstrating that cardiac and hepatic dysfunction emerged at 12 hours, followed by pulmonary, renal, neurological, and coagulatory failure at 24 hours. The validated MODS score was expected to offer a robust translational tool for timing therapeutic interventions.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Cohort Study on 28-Day Mortality in Immunosuppressed Sepsis: An Interpretability-Based Predictive Model Using MIMIC-IV v2.2.","authors":"Zhiru Zhong, Huiwei He, Zhiying Lin","doi":"10.1097/SHK.0000000000002721","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002721","url":null,"abstract":"<p><strong>Background: </strong>Sepsis in immunosuppressed patients is associated with significantly higher mortality rates, yet predictive models tailored to this high-risk population remain limited. This study aims to develop an interpretable machine learning model to predict 28-day mortality in immunosuppressed sepsis patients, with a focus on model transparency and clinical applicability.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using clinical, laboratory, and demographic data from immunosuppressed sepsis patients. Feature selection was performed using LASSO regression, followed by the development of predictive models, including XGBoost. The model's performance was evaluated using the area under the receiver operating characteristic curve (AUROC). To enhance clinical interpretability, Shapley Additive Explanations (SHAP) were employed to provide insights into the contribution of individual features to mortality predictions.</p><p><strong>Results: </strong>The final model identified key predictors of 28-day mortality, including lactate levels, red cell distribution width, platelet count, and Sequential Organ Failure Assessment (SOFA) score. XGBoost demonstrated superior predictive accuracy with an AUROC of 0.93 (95% CI: 0.90-0.96), outperforming other models. SHAP analysis revealed that elevated lactate levels and reduced platelet counts were strong risk factors for mortality, while lower lactate and higher platelet counts were protective. The model's interpretability provided clear insights into the role of each predictor, facilitating individualized risk stratification.</p><p><strong>Conclusion: </strong>The XGBoost model, combined with SHAP analysis, offers an accurate and interpretable tool for predicting 28-day mortality in immunosuppressed sepsis patients. This approach enhances clinical decision-making by providing transparent insights into the factors driving mortality risk, thus supporting personalized and timely interventions aimed at improving patient outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial and host inflammatory factors induce permeability and activate cytokine production by human glomerular microvascular endothelial cells.","authors":"Cindy Zhuang, Fengyun Xu, Kyle Tsutsui, Michael P Bokoch, Judith Hellman","doi":"10.1097/SHK.0000000000002702","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002702","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of Peripheral Monocytes Alters Long-Term Gene Expression in Microglia in a Murine Model of Traumatic Brain Injury.","authors":"Mecca B A R Islam, Zhangying Chen, Talia Just, Gaurav Gadhvi, Kacie P Ford, Booker T Davis, Hiam Abdala Valencia, Matthew Dapas, Hadijat M Makinde, Steven J Schwulst","doi":"10.1097/SHK.0000000000002695","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002695","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Traumatic brain injury (TBI) is a growing and under-recognized public health threat with significant long-term complications suffered by its survivors. Monocytes are amongst the first immune cells to infiltrate the injured brain and have the ability to both foster wound repair and promote inflammation. Microglia, the resident innate immune cells in the brain, drive the long-term direction of the inflammatory response within the injured brain. Previously published data from our laboratory has shown that a brief course of peri-injury monocyte depletion attenuates long-term neurocognitive deficits and preserves white matter connectivity post-injury. Nonetheless, the role that monocytes play in directing the local inflammatory response to injury via crosstalk with microglia remains unknown. To this end, we hypothesized that infiltrating monocytes shape the long-term transcriptional response of microglia to TBI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To test this hypothesis, we employed a 2x2 study design consisting of four experimental groups-TBI, sham, TBI with monocyte depletion, and TBI with sham monocyte depletion. Male C57BL/6 mice were randomly assigned to groups. Monocyte depletion and sham depletion were induced via intravenous injection of liposome-encapsulated clodronate versus naked liposomes 24 hour prior to TBI. Depletion was maintained via repeat injections on days 2 and 5. Monocyte depletion was confirmed via flow cytometry. TBI was induced using our established model of controlled cortical impact. Behavioral phenotyping was conducted at 30 days post-injury to assess motor coordination and memory. Mice were euthanized on post-injury days 1, 7, 14, 30, and 60. Brains were harvested and microglia sorted via flow cytometry. The transcriptional response of microglia across groups and timepoints was assess via bulk RNA sequencing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Monocyte-depleted mice demonstrated improvement in motor coordination, contextual and associative learning, and memory. These neurocognitive differences were associated with distinctly different microglial transcriptional profiles evident within the first 1-2 weeks post injury. In particular, microglia within the monocyte-depleted group showed distinct upregulation of pathways including synaptic signaling, regulation of neuron differentiation, and myeloid leukocyte activation as compared to those from Vehicle TBI groups. By 60 days post injury, microglia from the monocyte-depleted TBI group had upregulation of the heat shock protein transcripts as compared to microglia from the Vehicle TBI group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These data shows that short-course of peri-injury depletion of peripheral monocytes may have a neuroprotective effect after TBI. While the mechanisms of this protection are multifactorial, alteration of the long-term transcriptional profile of microglia may, in part, be responsible for the observed improvements in motor coordinatio","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality in the Sepsis-3 Era: A Systematic Review of Multicenter Randomized Controlled Trials.","authors":"Marko Nemet, I Serhat Karakus, G Cameron Gmehlin, Gabriele Alves Halpern, Kimia Ghafouri, Sergej Abramovich, Roshini Raghu, Mila Pastrak, Nasrin Nikravangolsefid, Gerberi J Dana, Svetlana Herasevich, Yewande Odeyemi, Amos Lal, Ognjen Gajic","doi":"10.1097/SHK.0000000000002687","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002687","url":null,"abstract":"<p><p>This systematic review examined multicenter randomized controlled trials (RCTs) conducted during the Sepsis-3 era that evaluated pharmaceutical and mechanistic interventions in adult patients with sepsis or septic shock, with a focus on identifying interventions that demonstrated mortality benefit. A comprehensive search was performed across Ovid MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, WHO ICTRP, and Web of Science for trials published since 2016. Studies were included if they enrolled adult patients with sepsis or septic shock using Sepsis-3 criteria and reported mortality as either a primary or secondary outcome. Data were extracted by two independent reviewers and included trial design characteristics, funding source, randomization methods, and reported outcomes. Among the 31 eligible multicenter RCTs enrolling over 7,000 patients across 550 centers, only four trials showed a mortality benefit. These included three studies from China-two evaluating herbal anti-inflammatory compounds and one evaluating aminophylline-and one European study assessing corticosteroid therapy in vasopressor-dependent septic shock. The remaining 27 trials reported no mortality benefit, and substantial heterogeneity was observed in patient populations, sepsis definitions, and outcome reporting. Median mortality in control arms was 31.6% (IQR 24.1-45.5), and 35.4% (IQR 25.7-49.6) in intervention arms. These findings suggest that despite extensive efforts, most interventions have not reduced mortality in multicenter sepsis trials. Future research should focus on optimizing trial design, refining patient selection, and incorporating patient-centered outcomes beyond mortality.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}