Critical Care最新文献

{"title":"Scoring system: use and not use from the future to present","authors":"Charles-Hervé Vacheron, Louis Brac, Albrice Levrat, Jean Stéphane David","doi":"10.1186/s13054-024-05081-0","DOIUrl":"https://doi.org/10.1186/s13054-024-05081-0","url":null,"abstract":"<p>We appreciated the letter from Wohlgemut and colleagues regarding the TIC score that we recently published in Critical Care [1, 2]. They highlight the value of this score for the early detection of traumatic coagulopathy, and recognize its ease of use upon hospital admission [2]. However, they challenged several points in our discussion regarding their Bayesian network score [3]. Briefly, they highlight the flexibility in modelling continuous variables, as well as the improved discrimination and calibration of their model. They suggest that prediction of coagulopathy is possible even with missing variables, which the TIC score theoretically cannot do. Finally, they suggest it may no longer be necessary to compromise model performance to achieve a simpler, more user-friendly model, due to advances in user interface design and user experience. It should be noted that we have deliberately chosen to compare our results with the model described by Yet B et al. because the model had good performance metrics and provides a realistic view of the causality of trauma-induced coagulopathy [3].</p><p>Their method relies on a set of data including clinical observation, physiological parameters, radiological findings and laboratory values being implemented automatically in a software application, enabling clinical decision making. Unfortunately, this does not currently match the reality of contemporary hospital care [4]. Furthermore, they argue that the Bayesian network scoring system can handle missing variables and estimate them from pre-existing data. We have chosen to include only pre-hospital parameters in our model, as they are immediately available at the time of admission or even during the pre-hospital phase of care. In our model, no parameters are missing at admission, except in rare cases when capillary hemoglobin measurement is not available. The score we described can be easily calculated mentally, driving immediate decision-making for the trauma patient [1]. The author's final point regarding the strength of Bayesian network analysis also reveals its weakness: weak diffusion. To our knowledge, the model has not been published and is therefore not reproducible by other centers, with the added difficulty of understanding and executing this analysis for the physician unfamiliar with such a model. There is also the “black box” issue, of using a model that obscures the weight of each variable, and its associated under-utilization in the medical field [5]. A simpler—but still accurate—scoring system not only provides a better understanding of the presence of trauma-induced coagulopathy, but also enables rapid and easy implementation of corrective therapy.</p><p>In conclusion, models such as Bayesian networks are currently rarely used, even though they represent a highly promising tool for the future of medicine. Until these techniques are ready for prime time, we believe it is still useful to have simple, pragmatic and easy-to-use tools to help doct","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"15 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should AI models be explainable to clinicians?","authors":"Gwénolé Abgrall, Andre L. Holder, Zaineb Chelly Dagdia, Karine Zeitouni, Xavier Monnet","doi":"10.1186/s13054-024-05005-y","DOIUrl":"https://doi.org/10.1186/s13054-024-05005-y","url":null,"abstract":"In the high-stakes realm of critical care, where daily decisions are crucial and clear communication is paramount, comprehending the rationale behind Artificial Intelligence (AI)-driven decisions appears essential. While AI has the potential to improve decision-making, its complexity can hinder comprehension and adherence to its recommendations. “Explainable AI” (XAI) aims to bridge this gap, enhancing confidence among patients and doctors. It also helps to meet regulatory transparency requirements, offers actionable insights, and promotes fairness and safety. Yet, defining explainability and standardising assessments are ongoing challenges and balancing performance and explainability can be needed, even if XAI is a growing field.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"312 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiopulmonary bypass and VA-ECMO induced immune dysfunction: common features and differences, a narrative review","authors":"Mathieu Lesouhaitier, Félicie Belicard, Jean-Marc Tadié","doi":"10.1186/s13054-024-05058-z","DOIUrl":"https://doi.org/10.1186/s13054-024-05058-z","url":null,"abstract":"Cardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation are critical tools in contemporary cardiac surgery and intensive care, respectively. While these techniques share similar components, their application contexts differ, leading to distinct immune dysfunctions which could explain the higher incidence of nosocomial infections among ECMO patients compared to those undergoing CPB. This review explores the immune modifications induced by these techniques, comparing their similarities and differences, and discussing potential treatments to restore immune function and prevent infections. The immune response to CPB and ECMO involves both humoral and cellular components. The kinin system, complement system, and coagulation cascade are rapidly activated upon blood contact with the circuit surfaces, leading to the release of pro-inflammatory mediators. Ischemia–reperfusion injury and the release of damage-associated molecular patterns further exacerbate the inflammatory response. Cellular responses involve platelets, neutrophils, monocytes, dendritic cells, B and T lymphocytes, and myeloid-derived suppressor cells, all of which undergo phenotypic and functional alterations, contributing to immunoparesis. Strategies to mitigate immune dysfunctions include reducing the inflammatory response during CPB/ECMO and enhancing immune functions. Approaches such as off-pump surgery, corticosteroids, complement inhibitors, leukocyte-depleting filters, and mechanical ventilation during CPB have shown varying degrees of success in clinical trials. Immunonutrition, particularly arginine supplementation, has also been explored with mixed results. These strategies aim to balance the inflammatory response and support immune function, potentially reducing infection rates and improving outcomes. In conclusion, both CPB and ECMO trigger significant immune alterations that increase susceptibility to nosocomial infections. Addressing these immune dysfunctions through targeted interventions is essential to improving patient outcomes in cardiac surgery and critical care settings. Future research should focus on refining these strategies and developing new approaches to better manage the immune response in patients undergoing CPB and ECMO. Although often considered similar, CPB and ECMO have distinct immune repercussions. Numerous immunomodulatory strategies have been tested in cardiac surgery patients undergoing CPB to mitigate the induced immunoparesis, but no clinical trials have been conducted for patients on ECMO. C5aR (complement component 5a receptor), CPB (cardiopulmonary bypass), DC (dendritic cells), ECMO (extracorporeal membrane oxygenation), HLA-DR (human leukocyte antigen-DR isotype), NETs (neutrophil extracellular traps), PD-1 (program cell death protein 1), ROS (reactive oxygen species), TLR (toll-like receptor). Created with BioRender.com ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"103 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of different statistical approaches in the comparison of dopamine and norepinephrine in the treatment of shock: SOAP II","authors":"Fernando G. Zampieri, Sean M. Bagshaw, Hassane Njimi, Jean-Louis Vincent, Daniel DeBacker","doi":"10.1186/s13054-024-05016-9","DOIUrl":"https://doi.org/10.1186/s13054-024-05016-9","url":null,"abstract":"Exploring clinical trial data using alternative methods may enhance original study’s findings and provide new insights. The SOAP II trial has been published more than 10 years ago; but there is still some speculation that some patients may benefit from dopamine administration for shock management. We aimed to reanalyse the trial under different approaches and evaluate for heterogeneity in treatment effect (HTE). All patients enrolled in SOAP II were eligible for reanalysis. We used a variety of methods including the win-ratio (WR), a Bayesian reanalysis stratified according to shock type, and both a risk-based and effect-based explorations for HTE. The methods were applied to different endpoints, including a hierarchy of death, new use of renal-replacement therapy (RRT), and new-onset arrhythmia; 28-day mortality; a composite endpoint (mortality, new use of RRT, and new-onset arrhythmia), and days alive and free of ICU at 28-days (DAFICU28). A total of 1679 patients were included (average age was 64.9 years, 57% male, 62% with septic and 17% with cardiogenic shock). All analysis favoured norepinephrine over dopamine. Under the WR approach, dopamine had fewer wins compared to norepinephrine (WR 0.79; 95% confidence intervals [CI] 0.68–0.92; p = 0.003), evident in both cardiogenic and septic shock subgroups. The Bayesian reanalysis for type of shock showed, for dopamine, a probability of harm of 0.95 for mortality, > 0.99 probability of harm for composite endpoint, and 0.91 probability of harm for DAFICU28. The fewer DAFICU28 with dopamine was more apparent in those with cardiogenic shock (0.92). Under the risk-based HTE, there was a high probability that dopamine resulted fewer DAFICU28 in the highest quartile of predicted mortality risk. The effect-based HTE assessment model did not recommended dopamine over norepinephrine for any combination of possible modifiers including age, type of shock, presence of cardiomyopathy, and SOFA score. Receiving dopamine when the effect-based model recommended norepinephrine was associated with an absolute increase in composite endpoint of 6%. The harm associated with the use of dopamine for the management of shock appears to be present in both septic and cardiogenic shock patients. There was no suggestion of any subgroup in which dopamine was found to be favourable over norepinephrine.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"9 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytomegalovirus end-organ disease in immunocompromised critically ill patients: key concerns demanding attention","authors":"Zhihui Zhang, Junlu Sun, Xuesong Liu, Rong Zhang, Yimin Li, Xiaoqing Liu","doi":"10.1186/s13054-024-05070-3","DOIUrl":"https://doi.org/10.1186/s13054-024-05070-3","url":null,"abstract":"<p>We delved into the clinical research conducted by Sara Fernández et al. [1] with great interest. This study is a multicenter, international research initiative spanning over a decade, primarily focusing on cytomegalovirus end-organ disease (CMV-EOD) among immunosuppressed patients with critical illness. The study revealed distinctive clinical features, risk factors, and adverse clinical outcomes in immunocompromised critically ill patients with CMV-EOD, marking it as a seminal work in the field. However, there is scope for enhancing the comprehensiveness of this study with further refinements.</p><p>First, within the specific population of immunocompromised critically ill patients, certain subjects (such as those with sepsis, trauma, and other prolonged illnesses) have been overlooked and excluded. Sepsis, a significant global health concern characterized by severe response to infection that causes organ failure, leads to over 5.3 million deaths yearly, with a mortality rate of around 30% [2,3,4]. Sepsis is currently understood to induce an imbalance in the immune system (innate and adaptive), leading to phenomenon known as \"immune paralysis\" [5,6,7]. The early stages (characterized by overwhelming inflammation) and the later stages (characterized by refractory inflammation, immunosuppression, and risk of secondary infections) of sepsis are both conducive to CMV reactivation [5,6,7,8]. The incidence of CMV reactivation in septic patients seems to be similar to other common immunosuppressed patients [8]. Our team's research indicates the incidence of CMV reactivation in critically ill patients with concurrent sepsis increases by at least 30%, and sepsis is an independent risk factor for CMV reactivation [9, 10]. This aligns with other mainstream research findings, where the underlying mechanism is associated with sepsis-induced immunosuppression, promoting CMV replication [11]. Therefore, definition of immunosuppressed population in CMV-EOD research should be broadened, and more effective immune function assessment indicators are required to clearly define \"immunocompromised\", moving beyond reliance on clinical disease types for judgment.</p><p>Second, assessing the impact of CMV load levels on clinical characteristics and outcomes in CMV-EOD population is essential. Additionally, it is necessary to evaluate CMV seropositivity, both qualitatively and quantitatively, as recent studies indicate a close relationship between CMV seropositivity and poor prognosis [12]. A combined assessment of CMV load and IgG in blood may enable earlier identification of high-risk patients, allowing for antiviral treatment to improve adverse outcomes. Third, the antiviral medications used for the subjects with CMV-EOD in this study may exert a negative influence on prognosis, primarily due to bone marrow suppression leading to a decrease in immune cell levels [13]. The use of the latest anti-CMV drugs Letermovir and Maribavir may mitigate these adverse effects [14]","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"16 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the timing of invasive mechanical ventilation in patients with sepsis: a multicenter cohort study","authors":"Gyungah Kim, Dong Kyu Oh, Su Yeon Lee, Mi Hyeon Park, Chae-Man Lim","doi":"10.1186/s13054-024-05064-1","DOIUrl":"https://doi.org/10.1186/s13054-024-05064-1","url":null,"abstract":"The potential adverse effects associated with invasive mechanical ventilation (MV) can lead to delayed decisions on starting MV. We aimed to explore the association between the timing of MV and the clinical outcomes in patients with sepsis ventilated in intensive care unit (ICU). We analyzed data of adult patients with sepsis between September 2019 and December 2021. Data was collected through the Korean Sepsis Alliance from 20 hospitals in Korea. Patients who were admitted to ICU and received MV were included in the study. Patients were divided into ‘early MV’ and ‘delayed MV’ groups based on whether they were on MV on the first day of ICU admission or later. Propensity score matching was applied, and patients in the two groups were compared on a 1:1 ratio to overcome bias between the groups. Outcomes including ICU mortality, hospital mortality, length of hospital and ICU stay, and organ failure at ICU discharge were compared. Out of 2440 patients on MV during ICU stay, 2119 ‘early MV’ and 321 ‘delayed MV’ cases were analyzed. The propensity score matching identified 295 patients in each group with similar baseline characteristics. ICU mortality was lower in ‘early MV’ group than ‘delayed MV’ group (36.3% vs. 46.4%; odds ratio, 0.66; 95% confidence interval, 0.47–0.93; p = 0.015). ‘Early MV’ group had lower in-hospital mortality, shorter ICU stay, and required tracheostomy less frequently than ‘delayed MV’ group. Multivariable logistic regression model identified ‘early MV’ as associated with lower ICU mortality (odds ratio, 0.38; 95% confidence interval, 0.29–0.50; p < 0.001). In patients with sepsis ventilated in ICU, earlier start (first day of ICU admission) of MV may be associated with lower mortality.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"23 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological monitoring and management for adult extracorporeal membrane oxygenation patients: Extracorporeal Life Support Organization consensus guidelines","authors":"Sung-Min Cho, Jaeho Hwang, Giovanni Chiarini, Marwa Amer, Marta V. Antonini, Nicholas Barrett, Jan Belohlavek, Daniel Brodie, Heidi J. Dalton, Rodrigo Diaz, Alyaa Elhazmi, Pouya Tahsili-Fahadan, Jonathon Fanning, John Fraser, Aparna Hoskote, Jae-Seung Jung, Christopher Lotz, Graeme MacLaren, Giles Peek, Angelo Polito, Jan Pudil, Lakshmi Raman, Kollengode Ramanathan, Dinis Dos Reis Miranda, Daniel Rob, Leonardo Salazar Rojas, Fabio Silvio Taccone, Glenn Whitman, Akram M. Zaaqoq, Roberto Lorusso","doi":"10.1186/s13054-024-05082-z","DOIUrl":"https://doi.org/10.1186/s13054-024-05082-z","url":null,"abstract":"Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"42 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid treatment increases cholesterol availability during critical illness: effect on adrenal and muscle function","authors":"Lauren De Bruyn, Arno Téblick, Tim Van Oudenhove, Sarah Vander Perre, Inge Derese, Lies Pauwels, Sarah Derde, Greet De Vlieger, Greet Van den Berghe, Lies Langouche","doi":"10.1186/s13054-024-05079-8","DOIUrl":"https://doi.org/10.1186/s13054-024-05079-8","url":null,"abstract":"Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. In a matched set of prolonged critically ill patients (n = 324) included in the EPaNIC RCT, a secondary analysis was performed to assess the association between glucocorticoid treatment and plasma cholesterol from ICU admission to day five. Next, in a mouse model of cecal ligation and puncture-induced sepsis, septic mice were randomized to receive either hydrocortisone (1.2 mg/day) (n = 17) or placebo (n = 15) for 5 days, as compared with healthy mice (n = 18). Plasma corticosterone, cholesterol, and adrenocortical and myofiber cholesterol were quantified. Adrenal structure and steroidogenic capacity were evaluated. Muscle force and markers of atrophy, fibrosis and regeneration were quantified. In a consecutive mouse study with identical design (n = 24), whole body composition was assessed by EchoMRI to investigate impact on lean mass, fat mass, total and free water. In human patients, glucocorticoid treatment was associated with higher plasma HDL- and LDL-cholesterol from respectively ICU day two and day three, up to day five (P < 0.05). Plasma corticosterone was no longer elevated in hydrocortisone-treated septic mice compared to placebo, whereas the sepsis-induced reduction in plasma HDL- and LDL-cholesterol and in adrenocortical cholesterol was attenuated (P < 0.05), but without improving the adrenocortical ACTH-induced CORT response and with increased adrenocortical inflammation and apoptosis (P < 0.05). Total body mass was further decreased in hydrocortisone-treated septic mice (P < 0.01) compared to placebo, with no additional effect on muscle mass, force or myofiber size. The sepsis-induced rise in markers of muscle atrophy and fibrosis was unaffected by hydrocortisone treatment, whereas markers of muscle regeneration were suppressed compared to placebo (P < 0.05). An increased loss of lean body mass and total and free water was observed in hydrocortisone-treated septic mice compared to placebo (P < 0.05). Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"51 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.","authors":"Christian Kassasseya, Ligia Iulia Torsin, Caroline Musset, Marc Benhamou, Irshad H Chaudry, Jean-Marc Cavaillon, Nathalie Grall, Renato Monteiro, Luc de Chaisemartin, Dan Longrois, Philippe Montravers, Christian de Tymowski","doi":"10.1186/s13054-024-05057-0","DOIUrl":"10.1186/s13054-024-05057-0","url":null,"abstract":"<p><strong>Introduction: </strong>Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy.</p><p><strong>Methods: </strong>The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered with PROSPERO (CRD42020167384) prior to data collection. PubMed and Embase were the databases queried. Risk of bias was evaluated using the SYRCLE Risk of Bias Tool. All animal studies investigating sepsis-related mortality and modified TNF signaling were considered eligible. The exclusion criteria were: lack of mortality data, 7-day mortality rates below 10% in both wild type and TNF-altered pathway animals, and absence of an English abstract. To determine the role of TNF according to the experimental protocol, three approaches were used: first an approach based on the statistical significance of each experiment, then the pooled mortality was calculated, and finally the weighted risk ratio for mortality was assessed.</p><p><strong>Results: </strong>A total of 175 studies were included in the analysis, comprising a total of 760 experiments and involving 19,899 animals. The main species used were mice (77%) and rats (21%). The most common method of TNF pathway modulation was TNF pathway inactivation that was primarily associated with an inappropriate secretion of TNF. At the opposite, TNF injection was associated with an adaptive role of TNF. Lipopolysaccharide (LPS) injection was the most used stimulus to establish an infectious model (42%) and was strongly associated with an inappropriate role of TNF. Conversely, live bacterial models, especially the cecal ligation and puncture (CLP) model, pneumonia, meningitis, and gastrointestinal infection, were associated with an adaptive role. This was particularly evident for Listeria monocytogenes, Streptococcus pneumoniae.</p><p><strong>Conclusion: </strong>The role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role.</p>","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"28 1","pages":"293"},"PeriodicalIF":8.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral physiologic insult burden in acute traumatic neural injury: a Canadian High Resolution-TBI (CAHR-TBI) descriptive analysis","authors":"Kevin Y. Stein, Alwyn Gomez, Donald Griesdale, Mypinder Sekhon, Francis Bernard, Clare Gallagher, Eric P. Thelin, Rahul Raj, Marcel Aries, Logan Froese, Andreas Kramer, Frederick A. Zeiler","doi":"10.1186/s13054-024-05083-y","DOIUrl":"https://doi.org/10.1186/s13054-024-05083-y","url":null,"abstract":"Over the recent decades, continuous multi-modal monitoring of cerebral physiology has gained increasing interest for its potential to help minimize secondary brain injury following moderate-to-severe acute traumatic neural injury (also termed traumatic brain injury; TBI). Despite this heightened interest, there has yet to be a comprehensive evaluation of the effects of derangements in multimodal cerebral physiology on global cerebral physiologic insult burden. In this study, we offer a multi-center descriptive analysis of the associations between deranged cerebral physiology and cerebral physiologic insult burden. Using data from the Canadian High-Resolution TBI (CAHR-TBI) Research Collaborative, a total of 369 complete patient datasets were acquired for the purposes of this study. For various cerebral physiologic metrics, patients were trichotomized into low, intermediate, and high cohorts based on mean values. Jonckheere–Terpstra testing was then used to assess for directional relationships between these cerebral physiologic metrics and various measures of cerebral physiologic insult burden. Contour plots were then created to illustrate the impact of preserved vs impaired cerebrovascular reactivity on these relationships. It was found that elevated intracranial pressure (ICP) was associated with more time spent with cerebral perfusion pressure (CPP) < 60 mmHg and more time with impaired cerebrovascular reactivity. Low CPP was associated with more time spent with ICP > 20 or 22 mmHg and more time spent with impaired cerebrovascular reactivity. Elevated cerebrovascular reactivity indices were associated with more time spent with CPP < 60 mmHg as well as ICP > 20 or 22 mmHg. Low brain tissue oxygenation (PbtO2) only demonstrated a significant association with more time spent with CPP < 60 mmHg. Low regional oxygen saturation (rSO2) failed to produce a statistically significant association with any particular measure of cerebral physiologic insult burden. Mean ICP, CPP and, cerebrovascular reactivity values demonstrate statistically significant associations with global cerebral physiologic insult burden; however, it is uncertain whether measures of oxygen delivery provide any significant insight into such insult burden.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"160 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}