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Background Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. Methods Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. Results Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. Conclusions Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. Level of evidence Prognostic, level III.

Background Deviation from guidelines is frequent in emergency situations and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HS) and severe traumatic brain injuries (TBI). Methods We first estimated the compliance with French and European guidelines using the data from the French TraumaBase® registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort. Results This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (RR = 0.91, 95%CI = 0.90-1.17, p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR = 0.85, 95%CI = 0.75-0.92, p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR = 0.46, 95%CI = 0.27-0.63, p = 0.01). In TBI, the bundle included 7 items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR = 0.55, 95%CI = 0.34-0.71, p = 0.02). Discussion Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner. Level of evidence II.

Background During the SARS-CoV-2 pandemic, the French Government imposed various containment strategies, such as severe lockdown (SL) or moderate lockdown (ML). The aim of this study was to evaluate the effect of both strategies on severe trauma admissions and ICU capacity in Ile-de-France region (Paris Area). Main text We conducted a multicenter cohort-based observational study from 1stJanuary 2017 to 31th December 2020, including all consecutive trauma patients admitted to the trauma centers of Ile-de-France region participating in the national registry (Traumabase®). Two periods were defined, the “non-pandemic period” (NPP) from 2017 to 2019, and the “pandemic period” (PP) concerning those admitted in 2020. The number of ICU beds released during 2020 pandemic period (overall period, SL and ML) was estimated by multiplying difference in trauma admissions by the median length of stay during the same week of pandemic period (ICU day-beds in 2020). A 15% yearly reduction of trauma patients was observed during the PP, associated with the release of 6422 ICU day-beds in 2020. During SL and ML, the observed decrease in trauma admission was respectively 49 and 39% compared with similar dates of the NPP. The number of beds released was 1531 days-beds in SL and 679 day-beds in ML. Those reductions respectively accounted for 4.5 and 6.0% of the overall ICU admission for COVID-19 in Ile-de-France. Conclusion The lockdown strategies during pandemic resulted in a reduction of severe trauma admissions. In addition to the social distancing effect, lockdown strategies freed up an important number of ICU beds in trauma centers, available for severe COVID-19 patients.

Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.Material and MethodsBlood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.ResultsSeveral features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion.ConclusionsGenomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.

Tranexamic acid (TXA) use in severe trauma remains controversial notably because of concerns of the applicability of the CRASH-2 study findings in mature trauma systems. The aim of our study was to evaluate the outcomes of TXA administration in severely injured trauma patients managed in a mature trauma care system.We performed a retrospective study of data prospectively collected in the TraumaBase registry (a regional registry collecting the prehospital and hospital data of trauma patients admitted in six Level I trauma centers in Paris Area, France). In hospital mortality was compared between patients having received TXA or not in the early phase of resuscitation among those presenting an unstable hemodynamic state. Propensity score for TXA administration was calculated and results were adjusted for this score. Hemodynamic instability was defined by the need of packed red blood cells (pRBC) transfusion and/or vasopressor administration in the emergency room (ER).Among patients meeting inclusion criteria (n = 1,476), the propensity score could be calculated in 797, and survival analysis could be achieved in 684 of 797. Four hundred seventy (59%) received TXA, and 327 (41%) did not. The overall hospital mortality rate was 25.7%. There was no effect of TXA use in the whole population but mortality was lowered by the use of TXA in patients requiring pRBC transfusion in the ER (hazard ratio, 0.3; 95% confidence interval, 0.3-0.6).The use of TXA in the management of severely injured trauma patients, in a mature trauma care system, was not associated with reduction in the hospital mortality. An independent association with a better survival was found in a selected population of patients requiring pRBC transfusion in the ER.Therapeutic study, level III.

Introduction: Balanced analgesia, using both opioid and non-opioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients. Material and Methods: A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were: postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the PACU (Postoperative Care Unit) stay and the early postoperative period (6 to 24 hours after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals. Results: Thirty five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6 to 24 hours) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6 to 24 hours) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid-sparing effect. Conclusions: This meta analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and non-opioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid-sparing effect.

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.