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Abstract Background Interferon gamma‑1b has been proposed to treat critical illness-induced immunosuppression. We aimed to determine the effects on 90-day outcomes and the cost-effectiveness of interferon gamma‑1b compared to placebo in mechanically ventilated critically ill patients. Methods A cost-effectiveness analysis (CEA) was embedded in the “PREV-HAP trial”, a multicenter, placebo‑controlled, randomized trial, which randomly assigned critically ill adults under mechanical ventilation to receive interferon gamma or placebo. The CEA compared interferon-gamma with placebo using a collective perspective at a 90-day time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed in terms of adjusted cost per adjusted Quality-Adjusted Life-Years (QALYs) gained. QALYs were estimated from the responses of patients and proxy respondents to the health-related quality of life questionnaire EQ-5D-3L. Results The 109 patients in the PREV-HAP trial were included in the CEA. At day 90, all-cause mortality rates were 23.6% in the interferon group and 25% in the placebo group (Odds Ratio (OR) = 0.88 (0.40 –1.93) p = 0.67). The difference in the mean adjusted costs per patient at 90 days was €-1.638 (95%CI €-17.534 to €11.968) in favor of interferon gamma-1b. The mean difference in adjusted QALYs between interferon gamma-1b and the placebo group was + 0.019 (95%CI -0.005 to 0.043). The probability that interferon gamma-1b was cost-effective ranged from 0.60 to 0.71 for a willingness to pay a QALY between €20k and €150k for the base case analysis. Conclusion Early administration of interferon gamma might be cost-effective in critically ill patients supporting the realization of other studies on this treatment. However, the generalization of the findings should be considered cautiously, given the small sample size due to the premature end of PREV-HAP. Trial registration ClinicalTrials.gov Identifier: NCT04793568, Registration date: 2021–02-24.

PurposeTranexamic acid (TXA) is the most widely prescribed antifibrinolytic for active bleeding or to prevent surgical bleeding. Despite numerous large multi-center randomized trials involving thousands of patients being conducted, TXA remains underutilized in indications where it has demonstrated efficacy and a lack of harmful effects. This narrative review aims to provide basic concepts about fibrinolysis and TXA’s mode of action and is focused on the most recent and important trials evaluating this drug in different hemorrhagic situations.MethodsWe selected every low bias RCT, and we highlighted their strengths and limitations throughout this review.Principal findingsWhile TXA appears to have a favorable benefit–risk ratio in most situations (trauma, obstetrics, at-risk for bleeding surgeries) evidence of benefit is lacking in certain medical settings (SAH, digestive bleeding).ConclusionAlthough in some situations the drug’s effect on significant outcomes is modest, its favorable safety profile allows it to be recommended for trauma patients, in obstetrics, and in scheduled surgeries at risk of bleeding. However, it cannot be recommended in cases of spontaneous intracranial bleeding, subarachnoid hemorrhage (SAH), or gastrointestinal bleeding.

Abstract Objective To describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation. Design Systematic review with an individual data meta-analysis. Setting Observational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes. Population Patients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h. Main outcome measures The primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio. Results The meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I 2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I 2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I 2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I 2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I 2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I 2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p

Traumatic brain injury (TBI) induces instant activation of innate immunity in brain tissue, followed by a systematization of the inflammatory response. The subsequent response, evolved to limit an overwhelming systemic inflammatory response and to induce healing, involves the autonomic nervous system, hormonal systems, and the regulation of immune cells. This physiological response induces an immunosuppression and tolerance state that promotes to the occurrence of secondary infections. This review describes the immunological consequences of TBI and highlights potential novel therapeutic approaches using immune modulation to restore homeostasis between the nervous system and innate immunity.

ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p