Explore the vast range of titles available.

Purpose To determine whether a liberal transfusion strategy (≥ 9 g/dL) improves neurological outcomes in adults with acute brain injury (ABI). Method We systematically searched MEDLINE, EMBASE, the Cochrane Library, and trial registries for randomized controlled trials comparing liberal (≥ 9 g/dL) vs. restrictive (≥ 7 g/dL) transfusion in adults with ABI (traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage) and Glasgow Coma Scale ≤ 13. Frequentist, Bayesian, and trial sequential analyses were used. The primary outcome was favorable neurological status at 180 days. Results Four randomized controlled trials ( N  = 1853; 922 liberal, 931 restrictive) were included. The pooled frequentist risk ratio (RR) for favorable neurological outcome was 0.84 (95% CI 0.65–1.09; I 2  = 58%). In a pre-specified sensitivity analysis including only low-risk-of-bias trials, the results suggested a potential benefit in favor of the liberal strategy (RR 0.74 [95% CI 0.63–0.87]) with no heterogeneity ( I 2  = 0%). Subgroup analyses for patients with traumatic brain injury or stratified by initial Glasgow coma scale were consistent with the main findings. Bayesian analyses showed that the estimated treatment effect depended on the assumptions and priors used, with an unfavorable prior derived from one trial with distinct protocol appearing less likely than neutral or favorable priors. Trial sequential analysis indicated that current evidence is insufficient to confirm a definitive effect. Secondary outcomes did not differ significantly between groups. Conclusions This review did not provide definitive evidence of a neurological benefit from liberal transfusion strategies in acute brain injury. Both frequentist and Bayesian analyses highlight the influence of a single trial on the overall effect estimate and heterogeneity. However, sensitivity analyses excluding this trial and focusing on studies with low risk of bias suggested that liberal transfusion strategies could improve neurological outcomes. Future research should focus on identifying patient subgroups most likely to benefit, guiding a more individualized approach.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development and complications remains unknown. In a cohort of patients with myeloproliferative neoplasm, JAK2V617F mutation was identified as an independent risk factor for dilation of both the ascending and descending thoracic aorta. Using single-cell RNA-seq, complementary genetically-modified mouse models, as well as pharmacological approaches, we found that JAK2V617F mutation was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages, and dissecting aneurysm through the recruitment of circulating monocytes at later stages. Finally, genetic manipulation of tissue-resident macrophages, or treatment with a Jak2 inhibitor, ruxolitinib, mitigated aortic wall inflammation and reduced aortic dilation and rupture. Overall, JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm. JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development remains unknown. Here, the authors show that JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

The aim of the present study was to evaluate the ability of the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content to predict an increase in oxygen consumption (VO2) upon fluid challenge (FC). 110 patients admitted to cardiothoracic ICU and in whom the physician had decided to perform an FC (with 500 ml of Ringer's lactate solution) were included. The arterial pressure, cardiac index (Ci), and arterial and venous blood gas levels were measured before and after FC. VO2 and CO2-O2 derived variables were calculated. VO2 responders were defined as patients showing more than a 15% increase in VO2. Of the 92 FC responders, 43 (46%) were VO2 responders. At baseline, pCO2 gap, C(a-v)O2 were lower in VO2 responders than in VO2 non-responders, and central venous oxygen saturation (ScvO2) was higher in VO2 responders. FC was associated with an increase in MAP, SV, and CI in both groups. With regard to ScvO2, FC was associated with an increase in VO2 non-responders and a decrease in VO2 responders. FC was associated with a decrease in pvCO2 and pCO2 gap in VO2 non-responders only. The pCO2 gap/C(a-v)O2 ratio and C(a-v)CO2 content /C(a-v)O2 content ratio did not change with FC. The CO2 gap content/C(a-v)O2 content ratio and the C(a-v)CO2 content /C(a-v)O2 content ratio did not predict fluid-induced VO2 changes (area under the curve (AUC) [95% confidence interval (CI)] = 0.52 [0.39‒0.64] and 0.53 [0.4-0.65], respectively; p = 0.757 and 0.71, respectively). ScvO2 predicted an increase of more than 15% in the VO2 (AUC [95%CI] = 0.67 [0.55‒0.78]; p<0.0001). Our results showed that the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content were not predictive of VO2 changes following fluid challenge in postoperative cardiac surgery patients.

Ischemic heart failure remains a major clinical challenge, underscoring the need to better understand post-infarction immune mechanisms and identify new therapeutic targets. Both innate and adaptive immunity contribute to adverse cardiac remodeling following myocardial infarction (MI), yet the role of cytotoxic cells such as natural killer (NK) cells remains poorly defined. Here, we show that after acute MI in mice, NK cells are recruited to the ischemic myocardium in a CCR2-dependent manner and become activated. Activated NK cells locally release granzyme B, promoting cardiomyocyte apoptosis, adverse ventricular remodeling, and impaired cardiac function. Genetic deletion or pharmacological depletion of NK cells reduces cardiomyocyte death, attenuates inflammation, limits myocardial injury, and improves cardiac function. In contrast, NK cell activation using an anti-NKG2A monoclonal antibody exacerbates ischemic heart failure. We further demonstrate that NK cells regulate bone marrow myelopoiesis through local GM-CSF production. Finally, we identify a distinct NK cellular and transcriptomic signature in human ischemic heart tissue at early stages. Together, these findings reveal a detrimental role for NK cells following acute MI and highlight NK cells as potential therapeutic targets to limit adverse cardiac remodeling. The immune mechanism causing ischemic heart failure pathology in myocardial infarction (MI) requires further exploration. The authors here find NK cells are recruited to ischemic heart after acute myocardial infarction (MI) and induce cardiomyocyte apoptosis. Pharmacological depletion of NK cells reduces the pathology.

IntroductionContinuous renal replacement therapy (CRRT) is a critical therapeutic intervention for patients with severe acute kidney injury in intensive care. However, premature filter clotting remains a significant challenge during CRRT, impacting treatment efficacy, costs and patient outcomes. Anticoagulation is essential to maintain circuit patency, with regional citrate anticoagulation (RCA) emerging as a preferred strategy due to its favourable bleeding profile. The standard target for post-filter ionised calcium (iCa) concentration during RCA-CRRT is set between 0.25 and 0.35 mmol/L, although evidence supporting this range is limited. We hypothesise that a higher post-filter iCa target (0.35–0.45 mmol/L) can provide comparable circuit patency while potentially reducing adverse effects associated with citrate administration.Methods and analysisThis multicentre randomised controlled non-inferiority trial will compare a low post-filter iCa target (0.25–0.35 mmol/L) with a higher post-filter iCa target (0.35–0.45 mmol/L) in patients undergoing RCA-CRRT in the intensive care unit. A total of 412 CRRT sessions will be randomised with a 1:1 ratio into these two groups. The primary outcome is the incidence of filter clotting. Secondary outcomes include filter lifespan, post-filter iCa levels, citrate infusion rates, the occurrence of metabolic adverse effects, financial costs and blood loss.Ethics and disseminationThe study has obtained approval from the ethics committee (Ethics Committee Est III, Nancy, France) and patients will be included after providing informed consent. The results will be disseminated at academic conferences and in peer-reviewed publications. All procedures were developed in order to assure data protection and confidentiality.Trial registration numberNCT05814341.

Cardiopulmonary bypass (CPB) during cardiac surgery leads to deleterious systemic inflammation. We hypothesized that TREM-1, a myeloid receptor shed after activation, drives systemic inflammation during CPB. Prospective observational bi-centric study. Blood analysis (flow cytometry and ELISA) before and at H2 and H24 after CPB. Inclusion of adult patients who underwent elective cardiac surgery with CPB. TREM-1 expression on neutrophils decreased between H0 and H2 while soluble (s)TREM-1 plasma levels increased. sTREM-1 levels increased at H2 and at H24 (  < 0.001). IL-6, IL-8, G-CSF and TNF-α, but not IL-1β, significantly increased at H2 compared to H0 (  < 0.001), but dropped at H24. Principal component analysis showed a close relationship between sTREM-1 and IL-8. Three patterns of patients were identified: Profile 1 with high baseline sTREM-1 levels and high increase and profile 2/3 with low/moderate baseline sTREM-1 levels and no/moderate increase overtime. Profile 1 patients developed more severe organ failure after CPB, with higher norepinephrine dose, higher SOFA score and more frequently acute kidney injury at both H24 and H48. Acute atrial fibrillation was also more frequent in profile 1 patients at H24 (80% vs. 19.4%,  = 0.001). After adjustment on age and duration of CPB, H0, H2 and H24 sTREM-1 levels remained associated with prolonged ICU and hospital length of stay. Baseline sTREM-1 levels as well as early kinetics after cardiac surgery identified patients at high risk of post-operative complications and prolonged length of stay.

The optimal tidal volume (TV) during one-lung ventilation (OLV) for thoracic surgery remains uncertain. This study aimed to evaluate the association between intraoperative tidal volume and the incidence of postoperative respiratory complications in patients undergoing thoracic surgery. We conducted a post-hoc analysis of single-center observational cohort study who underwent elective thoracic surgery with OLV between January 2015 and January 2021. Patients were categorized according to their mean intraoperative TV: < 5 mL/kg versus ≥ 5 mL/kg predicted body weight (PBW). The primary outcome was postoperative respiratory complications (PRCs) within 7 days. Secondary outcomes included other major complications and 30-/90-day mortality. Analyses were adjusted using propensity score overlap weighting. Sensitivity analyses included an alternative 6 mL/kg threshold and stratified analyses by TV range. A post hoc Bayesian analysis was also performed. We included 1,234 patients. PRCs occurred in 37/458 (8.1%) patients in the < 5 mL/kg group and 45/776 (5.8%) in the ≥ 5 mL/kg group. After adjustment, TV < 5 mL/kg was not associated with a reduced risk of PRCs (RR, 1.07; 95% CI, 0.69–1.66). Using a 6 mL/kg threshold yielded similar findings (RR, 0.93; 95% CI, 0.47–1.82). Stratified analyses by tidal volume range (> 4, 4–5, 5–6, and > 6 mL/kg) showed no significant association between tidal volume and PRCs. However, TV < 5 mL/kg was associated with an increased risk of postoperative atrial fibrillation (RR, 1.50; 95% CI, 1.09–2.05). Bayesian analyses showed no evidence of a beneficial effect of TV < 5 mL/kg on the composite outcome of postoperative complications, even when using favorable prior assumptions. In this cohort, tidal volumes < 5 mL/kg during OLV were not associated with a lower incidence of postoperative respiratory complications

Background The optimal timing for initiating norepinephrine in septic shock is debated. This updated systematic review and meta-analysis aimed to evaluate the impact of early versus delayed norepinephrine initiation on mortality and clinical outcomes in adults with septic shock. Methods A systematic search in Pubmed, EMbase and the Cochrane Library to identify eligible randomized controlled trials, propensity score matching (PSM) and observational studies that compare early norepinephrine initiation with non-early norepinephrine initiation in patients with acute circulatory failure. The primary outcome was mortality in intensive care unit. Secondary outcomes included intensive care unit length of stay, fluid volume received at 6 h, norepinephrine dose, mechanical ventilation-free days, renal replacement therapy free days, and time to achieve a targeted mean arterial pressure (MAP). Meta-analysis and subgroup analysis were conducted to calculate odds ratio (OR) or mean difference with 95% confidence interval (95%CI) using random-effect model. Trial sequential analysis was conducted to evaluate the conclusiveness of evidence. Results Ten studies (two RCT, three PSM and five observational studies) involving 4767 patients were included. Early norepinephrine significantly reduced mortality in RCT (OR 0.49, 95%CI 0.25–0.96; I 2  = 45%, p  = 0.04), pooled RCT and PSM (OR 0.65, 95%CI 0.42–0.99; I 2  = 74%, p  = 0.05), and observational studies (OR 0.71, 95%CI 0.54–0.94; I 2  = 66%). The trial sequential analysis indicated more data are needed. Subgroup analyses showed reduced mortality with early norepinephrine when lactate was ≤ 3mmol/L and administered within 1 h. Secondary outcomes showed a reduced fluid volume at 6h (RCT + PSM: mean difference −502 mL, 95%CI −899 to −106; I 2  = 91%, p  = 0.01), faster MAP target achievement (RCT + PSM: mean difference −1.30h, 95%CI −1.75 to −0.85; I 2  = 0%, p  < 0.01), more mechanical ventilation-free days (RCT + PSM: mean difference 3.99 days, 95%CI 2.42–5.57; I 2  = 32%, p  < 0.01) and smaller cumulative norepinephrine dose (Observational: mean difference –3.44 mcg/kg, 95%CI -6.13 to -0.76; I 2  = 0%, p = 0.01) in the early initiation group compare to the non-early initiation group. Conclusion Early norepinephrine introduction in septic shock is associated with reduced mortality, decreased fluid volume administered at 6 h, faster time to achieve MAP target and more mechanical ventilation-free days. However, the trial sequential analysis indicates that further RCT are still needed to confirm these findings.