BACKGROUND: Critical illness often causes prolonged weakness, possibly due to impaired skeletal muscle regeneration, but the timing and nature of satellite cell (SC) dysfunction remain unclear. We aimed to determine whet...BACKGROUND: Critical illness often causes prolonged weakness, possibly due to impaired skeletal muscle regeneration, but the timing and nature of satellite cell (SC) dysfunction remain unclear. We aimed to determine whether SC depletion and dysfunction are detectable early after intensive care unit admission and describe their pathophysiological nature. METHODS: In this prospective single-centre observational cohort study, mechanically ventilated adults underwent paired vastus lateralis biopsies within 72 h of ICU admission and again after 7 and 180 days. Isolated satellite cells were studied for proliferation, differentiation and fusion, mitochondrial morphology, respiratory function, substrate oxidation, and selected signalling proteins. RESULTS: We enrolled 20 healthy control subjects and 33 ICU patients. Twenty three ICU patients survived to day 7 with a repeat biopsy. During 7 days in ICU, the patient developed profound weakness (MRC score 16 [0-32]) and insulin resistance (whole body glucose disposal 4.0 [3.5-5.1] versus 13.8 [8.8-16.1] mg/kg/min in controls). Satellite cell number per fibre was similar in controls and patients at admission (0.106 [0.085-0.129] vs. 0.098 [0.056-0.125]) and after 7 days (0.084 [0.066-0.117]; paired p = 0.784). SC proliferation was lower in older patients (ρ=-0.68 and - 0.49) and associated with lower muscle strength (ρ = 0.55 and 0.62). Myogenic differentiation was transiently impaired at day 0 (fusion index 68.9% [66.3-71.7] vs. 74.0% [70.3-77.1] in controls; p = 0.029). Satellite cell bioenergetics and substrate preferences were broadly preserved. In contrast, a more fragmented mitochondrial phenotype was associated with lower proliferation, lower respiratory performance, and worse muscle strength (ρ≈-0.6 to -0.8), whereas more interconnected morphology was associated with better function (ρ ≈ 0.6-0.7). Out of 10 ICU survivors at day 180, only 7 attended follow up. In those, impaired SF-36 physical score (62.5 [55.0 to 75.0]) and SC proliferation capacity (~50 %), contrasted with improved insulin sensitivity and SC number per fiber (~71 % and ~95% of control values, respectively). CONCLUSIONS: Critical illness was associated with disturbed satellite cell regenerative programming and altered mitochondrial remodelling rather than early depletion of the satellite cell pool or overt bioenergetic failure. Age was a stronger predictor of early satellite cell dysfunction than disease severity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05671614. Registered 4 January 2023.
Marinho LL, Lileikyte G, Boileau P
… +19 more, Lu Y, Churpek M, Spicer A, Harhay M, Chen Z, Luk A, Zampieri FG, Tavares CAM, Proudfoot A, Pop C, Deschênes PJF, Zarychanzki R, Lother S, Abrahão Hajjar L, Jentzer JC, van Diepen S, di Santo P, Mathew R, Lawler PR
A dysregulated host response to infection is central to the pathophysiology of sepsis and may culminate in life-threatening organ dysfunction. Given that this process is largely characterized by concurrent pro- and anti-...A dysregulated host response to infection is central to the pathophysiology of sepsis and may culminate in life-threatening organ dysfunction. Given that this process is largely characterized by concurrent pro- and anti-inflammatory activation, immunomodulatory strategies have long been explored in sepsis research. Among these, extracorporeal removal of circulating cytokines, inflammatory mediators and other soluble factors through non-specific hemoadsorption with macroporous styrene-divinylbenzene sorbents has been proposed as a potential therapeutic approach. Its adoption into clinical practice has largely been based on pathophysiological considerations rather than on evidence from large, well-designed randomized clinical trials. Over the past 15 years, most of the available evidence has been predominantly derived from small, single-center cohorts, reports from registries and heterogeneous prospective studies with substantial variability in patients' selection, timing, and treatment intensity. In addition, the precise mechanisms of action of hemoadsorption remain incompletely understood. Although several meta-analyses have attempted to synthesize the existing data, the overall quality and heterogeneity of the included studies limit the strength and reliability of their conclusions. As a result, current guideline recommendations are largely based on expert opinions rather than high-certainty evidence. This position statement aimed to provide a concise overview of the biological rationale, current evidence, and contemporary clinical practice related to hemoadsorption in critically ill patients.
BACKGROUND: Management after severe traumatic brain injury (TBI) aims to prevent secondary injury by optimizing cerebral physiology, yet conventional metrics such as intracranial pressure (ICP) and cerebral perfusion pre...BACKGROUND: Management after severe traumatic brain injury (TBI) aims to prevent secondary injury by optimizing cerebral physiology, yet conventional metrics such as intracranial pressure (ICP) and cerebral perfusion pressure (CPP) incompletely capture the underlying pathophysiology. Impaired cerebral pressure autoregulation (CPA) is common and may exacerbate secondary injury. Proteomic blood-based biomarkers (PBBMs) of astrocytic (glial fibrillary acidic protein [GFAP], S100 calcium-binding protein B [S100B]), and neuronal/axonal injury (total tubulin associated unit [t-Tau], neurofilament light chain [NfL], ubiquitin C-terminal hydrolase-L1 [UCH-L1], neuron-specific enolase [NSE]) may provide global indicators of secondary injury. This study investigated temporal associations between PBBMs and cerebral physiological variables (ICP, CPP, pressure reactivity index [PRx], and CPP deviation from "optimal" CPP [ΔCPPopt]), and evaluated the PBBMs as surrogate short-term endpoints. METHODS: This retrospective, observational multi-center study, used prospective data from the CENTER-TBI cohort and included 151 patients with high-frequency cerebral physiological data and serial PBBM measurements during the first seven days post-injury. Associations were analyzed using Spearman correlations, univariate and multivariate linear mixed effects models (LMEMs), as well as cross correlation analyses adjusted for repeated measures and clinical confounders. RESULTS: Elevated PBBM levels on day 1 were associated with a greater cumulative burden of high ICP, impaired CPA (positive PRx), and negative ΔCPPopt over the subsequent seven days. Throughout the monitoring period, higher median PBBM concentrations correlated with elevated ICP and impaired CPA, with strongest associations when cerebral physiological monitoring and PBBMs were analyzed from the same day. In multivariate LMEMs, elevated ICP and most PBBMs remained significantly associated, while particularly PRx amplified this association. CONCLUSIONS: Cerebral physiological disturbances during intensive care after TBI were associated with elevated PBBM levels, with ICP showing the strongest influence and impaired CPA amplifying some PBBM responses. Associations were strongest in same-day analyses and appeared bidirectional. These findings suggest that PBBM may reflect the burden of secondary cerebral insults and may serve as candidate endpoints for future trials targeting cerebral physiology, pending validation in prospective high-resolution studies. Importantly, our results highlight the potential for PBBMs to complement multimodal neuromonitoring by tracking secondary injury trajectories.
Norepinephrine is the first-line vasopressor in septic shock, yet prolonged catecholamine exposure is associated with adverse effects that have prompted growing interest in catecholamine-sparing strategies. This review h...Norepinephrine is the first-line vasopressor in septic shock, yet prolonged catecholamine exposure is associated with adverse effects that have prompted growing interest in catecholamine-sparing strategies. This review highlights current evidence on the rationale for catecholamine use, the burden of sustained adrenergic exposure, and current and emerging sparing strategies. Early norepinephrine initiation, including via peripheral access, shortens hypotension duration and reduces fluid requirements. However, catecholamine exposure can carry dose-dependent cardiac, metabolic, and immunological consequences. Perfusion-guided strategies, including individualization of blood pressure targets and titration of vasopressor use based on capillary refill time, represent the cornerstone of reduction of catecholamines. Among alternative non-adrenergic vasopressors, vasopressin reduces catecholamine exposure and the risk of atrial fibrillation, with potential renal benefits. Angiotensin II represents an option in catecholamine-refractory shock, with post-hoc evidence suggesting benefit in patients with acute kidney injury or elevated renin concentrations. Inhibition of circulating dipeptidyl peptidase 3, which degrades angiotensin II, is an emerging therapeutic strategy. Corticosteroids restore vasopressor sensitivity and accelerate catecholamine weaning. Short-acting β1-blockers have shown hemodynamic promise but inconsistent outcomes, underscoring the need for better patient selection. Methylene blue, targeting the vasodilatory nitric oxide pathway, represents another strategy. Finally, emerging immunomodulatory approaches, including extracellular histone neutralization and polymyxin B hemoperfusion in endotoxin phenotypes, aim to attenuate the dysregulated host response driving vasopressor dependency. A personalized and multimodal approach, including perfusion-guided targets, non-adrenergic vasopressors, and phenotype-based patient selection, represents the most promising strategy to reduce potential consequences of adrenergic burden while maintaining tissue perfusion.
BACKGROUND: Nutritional therapy is a key component of critical care management, yet optimal strategies remain debated due to the heterogeneity of ICU patients, dynamic metabolic alterations, and the profound influence of...BACKGROUND: Nutritional therapy is a key component of critical care management, yet optimal strategies remain debated due to the heterogeneity of ICU patients, dynamic metabolic alterations, and the profound influence of inflammation on nutrient utilisation. Evidence from recent trials has challenged traditional one-size-fits-all approaches, emphasising the need for individualised, phase-specific nutrition throughout the continuum of critical illness and recovery. This manuscript summarises current concepts and emerging evidence in nutrition therapy presented at the 39th Annual Conference of the German Society for Nutritional Medicine (DGEM). Experts reviewed and critically discussed inflammation-driven metabolic changes, personalised energy and protein prescriptions, micronutrient management, macronutrient adaptation, ketogenic strategies in neurocritical care and sepsis, and nutritional considerations in post-ICU syndrome and outpatient recovery. This overview does not claim to be exhaustive; interpretations of individual study results partly reflect the views of the experts. Together with the inclusion of newer therapeutic approaches, this is intended to stimulate discussion and, at the same time, provide a basis for further studies. MAIN BODY: Inflammation and high disease severity strongly influence nutritional responsiveness, with highly inflamed patients demonstrating reduced benefit and heightened risk of overfeeding. Personalised strategies, including indirect calorimetry, fat-free mass-based protein dosing, and metabolic biomarkers such as the urea-creatinine ratio, offer a rational framework for tailoring therapy. Micronutrient deficiencies are common due to redistribution, pre-existing deficits, and extracorporeal losses, necessitating structured assessment and supplementation. Macronutrient delivery should be progressively escalated and regarded as a pharmacologic intervention aligned with disease phase and organ function. Early standardised ketogenic diet protocols show feasibility and potential clinical benefit in refractory status epilepticus and sepsis. Post-ICU and outpatient phases remain nutritionally vulnerable, with persistent catabolism and underfeeding common; structured, multidisciplinary rehabilitation and transitional nutrition programs may improve long-term outcomes. CONCLUSION: Future personalised nutrition strategies may rely on metabolic phenotyping and biomarker-informed stratification rather than uniform protein, energy and micronutrient targets for all ICU patients. Integrating individualised energy and protein prescription, targeted micronutrient management, emerging metabolic therapies, and coordinated post-ICU rehabilitation may optimise recovery and functional outcomes. Robust clinical trials are needed to confirm the impact of these personalised strategies on long-term patient-centred endpoints.
Patient-specific computational tools hold great promise for the development of more personalized treatment strategies for acute respiratory failure. Such tools span a continuum from data-driven predictors, to patient-spe...Patient-specific computational tools hold great promise for the development of more personalized treatment strategies for acute respiratory failure. Such tools span a continuum from data-driven predictors, to patient-specific mechanistic models, and ultimately to fully realized digital twins with continuous bidirectional model-patient interactions. Data-driven prediction models apply machine learning to large-scale patient datasets to develop tools that can help clinicians identify patients who are likely, or unlikely, to benefit from a particular course of treatment. By incorporating detailed computational representations of disease pathophysiology, patient-specific mechanistic models can provide insights into the effects of existing or novel treatment strategies, support patient stratification and treatment personalization, and enable the design of in silico clinical trials of new interventions. Finally, fully realized dynamic digital twins of patients could provide real-time decision support and 'simulate-before-treat' capabilities at the bedside, helping clinicians optimize treatment as the patient's disease state evolves. This narrative review provides an overview of recent research applying these approaches in the context of acute respiratory failure, encompassing both respiratory and ventilatory support across neonatal, paediatric and adult populations, and pre-hospital, ward and intensive care environments.
BACKGROUND: Inflammatory cytokines play a pivotal role in septic shock, driving tissue injury and circulatory failure. Hemoadsorption has been proposed as an extracorporeal strategy that removes inflammatory mediators. P...BACKGROUND: Inflammatory cytokines play a pivotal role in septic shock, driving tissue injury and circulatory failure. Hemoadsorption has been proposed as an extracorporeal strategy that removes inflammatory mediators. Patient selection and treatment timing may be integral to clinical benefit. OBJECTIVES: To determine whether adjunctive hemoadsorption with the HA-330 cytokine adsorber reduces 28-day mortality in patients with septic shock requiring high-dose vasopressors, compared with standard treatment alone. METHODS: This multicenter, randomized controlled trial enrolled patients with septic shock requiring norepinephrine ≥ 0.2 mcg/kg/min at two tertiary care centers in Thailand. Participants were assigned 1:1 to standard treatment alone (ST group) or standard treatment with two 3-hour sessions of hemoadsorption using HA-330 (HA group). The primary outcome was 28-day mortality. The trial was terminated early at the second pre-planned interim analysis due to slow recruitment and funding constraints before reaching the planned sample size of 206 participants. RESULTS: A total of 128 participants were enrolled; 65 were assigned to the ST group and 63 to the HA group. The median age was 67 years, and baseline characteristics were largely comparable between groups. By day 28, 38 of 65 (58%) participants in the ST group and 28 of 63 (44%) in the HA group had died (relative risk, 0.76; 95% CI, 0.54-1.07; P = 0.16; hazard ratio, 0.68; 95% CI, 0.44-1.07; P = 0.09). No significant differences were observed in organ support-free days, shock reversal, vasopressor doses, or inflammatory markers. In a post-hoc Cox model adjusted for IL-6 (log-transformed) and VIS at hour 0, the hazard ratio for 28-day mortality was 0.62 (95% CI, 0.39-0.97; P = 0.037). No serious adverse events were reported in either group. CONCLUSIONS: In this randomized trial which was terminated early, adjunctive hemoadsorption with HA-330 in patients with septic shock requiring high-dose vasopressors did not statistically reduce 28-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05136183); registered November 29, 2021.
Piva S, Bertoni M, Barbieri S
… +15 more, Chieregato A, Chevallard G, Contarino R, Lazzaroni M, Lucchini A, Monti G, Peli E, Pozzi M, Previtali P, Querci L, Rasulo F, Renzetti S, Spadaro S, Tardini F, Latronico N
BACKGROUND: Fatigue is a common and disabling sequela among survivors of critical illness, yet its long-term trajectory and clinical correlates during recovery remain poorly understood, particularly its dynamic evolution...BACKGROUND: Fatigue is a common and disabling sequela among survivors of critical illness, yet its long-term trajectory and clinical correlates during recovery remain poorly understood, particularly its dynamic evolution over time and its relationship with physical and psychological domains of recovery. METHODS: We conducted a prospective multicenter observational study embedded in a structured ICU follow-up program across six Italian hospitals. Outcomes were assessed during standardized in-person visits at 3, 6, 12, and 24 months after ICU discharge. Fatigue was assessed using the Fatigue Severity Scale (FSS; severe fatigue defined as FSS ≥36). Muscle strength and functional exercise capacity were evaluated using handgrip dynamometry and the six-minute walk test (6MWT), and psychological symptoms using the Hospital Anxiety and Depression Scale (HADS). Generalized linear mixed models (GLMM) with time-lagged variables were used to examine whether clinical measures at one visit were associated with severe fatigue at the subsequent visit, including prior fatigue status to account for preceding fatigue burden. RESULTS: A total of 1,912 ICU survivors attended at least one follow-up visit, of whom 976 patients (51%) experienced severe fatigue at least once. The prevalence of severe fatigue was 336/967 (34.7%) at 3 months, 628/1,522 (41.3%) at 6 months, 434/1,135 (38.2%) at 12 months, and 64/217 (29.5%) at 24 months. Persistent severe fatigue across multiple visits was observed in 655 patients (34.3%), and individual trajectories were heterogeneous over time. In GLMM with time-lagged variable, prior fatigue status (OR 3.00, 95% CI 1.31-6.84), lower functional exercise capacity on the 6MWT (OR 0.77, 95% CI 0.61-0.95), and symptoms of anxiety (OR 6.76, 95% CI 2.01-22.68) and depression (OR 17.8, 95% CI 4.16-76.47), all measured at the preceding visit, were associated with severe fatigue at the subsequent visit. CONCLUSIONS: Severe fatigue remained common up to 24 months after ICU discharge, with heterogeneous trajectories over time and persistent severe fatigue affecting approximately one-third of survivors. Prior fatigue status, lower functional exercise capacity, and psychological distress were associated with subsequent fatigue, supporting the value of multidimensional assessment of recovery within structured ICU follow-up programs.
BACKGROUND: Ventilator-induced diaphragm dysfunction (VIDD) is a frequent and under-recognized consequence of prolonged mechanical ventilation in intensive-care unit (ICU) patients. Identifying eligible candidates for cl...BACKGROUND: Ventilator-induced diaphragm dysfunction (VIDD) is a frequent and under-recognized consequence of prolonged mechanical ventilation in intensive-care unit (ICU) patients. Identifying eligible candidates for clinical trials targeting VIDD remains a major operational challenge. This study evaluates the use of large language models (LLMs) to automate patient prescreening from ICU discharge summaries and estimate recruitment capacity for a future phase 2 trial. METHODS: We developed an LLM-based prescreening pipeline to assess trial eligibility criteria from ICU discharge summaries, which was deployed to screen all 2024 ICU stays. Stays that were flagged as potentially eligible underwent expert adjudication. An enriched set of 50 ICU stays was independently annotated by six clinicians to define a reference standard, which was used to evaluate criterion-level model performances using F1-scores. RESULTS: The best-performing model was GPT-OSS:120B with a criterion-level F1-score of 0.82. When applied to consecutive 1,342 ICU stays from Montpellier University Hospital in 2024, the selected model identified 532 patients with ≥ 3 days of mechanical ventilation. After applying exclusion criteria, 185 patients remained potentially eligible. Expert review confirmed 133 patients as eligible, resulting in a positive predictive value of 72% (95% CI 65-78). The LLM-assisted workflow resulted in an estimated 86% reduction in clinician review time. The LLM-based prescreening pipelines achieved criterion-level F1 scores ranging from 0.73 to 0.82, with GPT-OSS:120B demonstrating the highest performance. CONCLUSIONS: LLM-based prescreening offers a promising approach for identifying trial candidates in critical care, prioritizing candidates for clinician review. Future deployments should include targeted expert validation and ongoing monitoring to ensure safety and generalizability.
BACKGROUND: Spontaneous cerebellar hemorrhage (sCH) is a severe condition, due to the limited space in the posterior fossa. The temporal dynamics of cerebral physiological variables such as intracranial pressure (ICP), p...BACKGROUND: Spontaneous cerebellar hemorrhage (sCH) is a severe condition, due to the limited space in the posterior fossa. The temporal dynamics of cerebral physiological variables such as intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), "optimal" CPP (CPPopt), and CPP deviation from CPPopt (ΔCPPopt) and associations with functional outcome remain insufficiently characterized in sCH. METHODS: This study retrospectively analyzed 94 adult sCH patients treated at the neurointensive care (NIC) unit in Uppsala University Hospital, Sweden, between 2008 and 2024, with collected high resolution monitoring data. The association between insult intensity-duration, temporal dynamics, and interactions with cerebrovascular autoregulation of the cerebral physiological variables with Glasgow Outcome Scale at discharge (GODS) were analyzed in outcome heatmaps. Formal statistical analyses between % of good monitoring time (%GMT) of the cerebral physiological variables within/outside certain thresholds were analyzed in relation to GODS. RESULTS: In the exploratory analyses, ICP > 15 mmHg demonstrated a descriptive trend toward unfavorable outcome irrespective of duration, particularly the first two days post-injury. Still, the association lacked significance (p = 0.85). Sustained PRx elevations > 0.2 showed a descriptive trend toward worse outcome, with expanding vulnerability over time. However, this association was not significant (p = 0.26). CPP < 80 mmHg was associated with worse outcome, particularly if PRx was elevated. In addition, CPP < 60 mmHg was associated with worse outcome, while CPP > 80 mmHg was associated with favorable outcome (p = 0.02, respectively). Negative ΔCPPopt for longer durations and if PRx was elevated correlated with lower GODS. ΔCPPopt < -5 mmHg was associated with worse outcome (p = 0.04). CONCLUSIONS: Cerebral physiological monitoring provides important prognostic information in sCH. Optimal targets differ from supratentorial acute brain injuries, with an apparent benefit of higher CPP in sCH. ICP, CPP, and ΔCPPopt remain central, warranting larger multi-center studies to define sCH-specific targets.
BACKGROUND: The understanding of acute kidney injury (AKI) has evolved, but it remains uncertain whether outcomes have improved over time. This study aimed to describe temporal changes in outcomes among intensive care un...BACKGROUND: The understanding of acute kidney injury (AKI) has evolved, but it remains uncertain whether outcomes have improved over time. This study aimed to describe temporal changes in outcomes among intensive care unit (ICU) patients with AKI in Denmark from 2010 to 2024. METHODS: This cohort study included adult patients with a first-time ICU admission, and AKI identified using creatinine changes in the seven days following ICU admission. The risks of chronic kidney disease (CKD), kidney failure (KF), and death were assessed one year after ICU admission across three periods: 2010-2014, 2015-2019, and 2020-2024. CKD was defined as an outpatient estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 for more than 90 days. Similarly, KF was defined as an eGFR below 15 ml/min/1.73 m2, a hospital diagnosis, kidney transplantation, or initiation of chronic kidney replacement therapy. Follow-up was divided into seven to 89 days and from 90 to 365 days, and death was considered a competing risk for CKD and KF. RESULTS: A total of 48,529 patients with AKI were identified. The seven to 89-day mortality was 23.4% (95% confidence interval (CI): 22.5%-24.3%) in 2010-2014, compared to 22.3% (95% CI: 21.7%-22.9%) in 2015-2019, and 20.7% (95% CI: 20.2%-21.2%) in 2020-2024. The 90- to 365-day mortality was 10.3% (95% CI: 9.5%-11.0%) in 2010-2014, 10.2% (95% CI: 9.7%-10.7%) in 2015-2019, and 9.5% (95% CI: 9.1%-10.0%) in 2020-2024. The 90- to 365-day risk of CKD was 21.0% (95% CI: 19.9%-22.1%) in 2010-2014, compared to 19.8% (95% CI: 19.1%-20.6%) in 2015-2019 and 17.3% (95% CI: 16.7%-17.9%) in 2020-2024. The 90- to 365-day risk of KF was 2.2% (95% CI: 1.9%-2.6%) in 2010-2014, 2.1% (95% CI: 1.9%-2.3%) in 2015-2019, and 2.0% (95% CI: 1.8%-2.3%) in 2020-2024. CONCLUSIONS: In this cohort of ICU patients with AKI, mortality and risk of CKD decreased over time, while the risk of KF remained stable. These improvements are encouraging and may reflect changes in ICU management or post-AKI care, although the observational design precludes inference about underlying mechanisms.
BACKGROUND: Out-of-hospital cardiac arrest (OHCA) due to aneurysmal subarachnoid hemorrhage (aSAH) is rare but associated with extremely poor prognosis. Data on neurological outcomes and prognostic factors are limited. M...BACKGROUND: Out-of-hospital cardiac arrest (OHCA) due to aneurysmal subarachnoid hemorrhage (aSAH) is rare but associated with extremely poor prognosis. Data on neurological outcomes and prognostic factors are limited. METHODS: We conducted a retrospective multicenter cohort study across 12 French neuro-ICUs including all adult patients admitted alive after OHCA-aSAH between 2014 and 2024. Demographics, cardiac arrest characteristics, aSAH severity, ICU management, and 6-month neurological outcomes (modified Rankin Scale, mRS) were collected. Firth penalized logistic regression was applied to explore predictors of favorable outcome. RESULTS: Among 15,907 SAH admissions, 164 patients had OHCA-aSAH. Median age was 54 [43-62] years; 47.5% were male. Only 8 patients (4.9%) achieved favorable outcome (mRS ≤ 3) while 156 (95.1%) had poor outcome (mRS ≥ 4), including 154 deaths (mRS 6). Low-flow duration tended to be shorter, epinephrine use lower, and pupillary abnormalities less frequent among survivors, although no independent statistical association could be confirmed. All patients receiving pre-hospital antiplatelet or anticoagulant therapy (n = 14, 8.7%) had poor outcome. External ventricular drainage, ICP monitoring, and endovascular aneurysm treatment were more frequent, and ICU and hospital length of stay were longer, in survivors. One hundred and eight patients (65.8%) progressed to brain death within 1 [1-2] day. Penalized regression did not identify independent predictors of good outcome, though pupillary abnormalities and epinephrine use were associated with progression toward brain death. CONCLUSIONS: OHCA-aSAH carries a dismal prognosis, with < 5% achieving favorable neurological recovery. Selected patients may benefit from aggressive neurocritical care, and the high rate of brain death emphasizes the importance of organ donation pathways.
BACKGROUND: In sepsis, personalized immunotherapy is being evaluated as a strategy to restore immune function in the most severely affected patients. Biomarkers are critical in this process, as clear clinical indicators...BACKGROUND: In sepsis, personalized immunotherapy is being evaluated as a strategy to restore immune function in the most severely affected patients. Biomarkers are critical in this process, as clear clinical indicators of immune status are lacking. Functional testing is considered the gold standard for assessing immune function, but its clinical implementation faces analytical and standardization challenges. The objective of the present prospective, observational, single-center cohort study was to evaluate a fully automated protocol for assessing T cell functionality in septic shock patients. METHODS: In 66 patients with septic shock, we assessed T lymphocyte functionality using an interferon-γ release assay (IGRA) in response to mitogen. The assay was performed via a fully automated protocol during a one-year period. Patients were monitored three times during the first week after intensive care unit (ICU) admission. Phenotypic immunological parameters, including T cell subpopulation counts and monocyte HLA-DR expression (mHLA-DR), were also assessed. Patient outcomes were followed for 28 days, and a composite clinical deterioration score was defined by the occurrence of 28-day mortality and/or ICU-acquired infection. RESULTS: Compared with reference values, we observed a significant reduction in IFN-γ release capacity, which correlated with characteristic alterations in cellular immunological parameters. By the end of the first week, reduced IFN-γ release combined with low mHLA-DR identified a severe immunological phenotype associated with an increased risk of clinical deterioration. CONCLUSION: Given the observational nature of this study, further well-designed investigations in larger patient cohorts are required to validate these findings and assess their potential clinical relevance. If confirmed, this fully automated assay (performed on whole blood, requiring no technician intervention, and providing results within four hours) may offer a practical tool for monitoring immune functional alterations in routine clinical practice.
BACKGROUND: Mechanical ventilation is routinely used during veno-arterial extracorporeal membrane oxygenation (V-A ECMO), but its role in influencing hemodynamics and supporting cardiac recovery remains poorly understood...BACKGROUND: Mechanical ventilation is routinely used during veno-arterial extracorporeal membrane oxygenation (V-A ECMO), but its role in influencing hemodynamics and supporting cardiac recovery remains poorly understood. This systematic review aims to summarize and describe studies that investigated the effects of mechanical ventilation settings and adjunctive respiratory interventions on cardiac function, recovery, and clinical outcomes in V-A ECMO patients. METHODS: A systematic search in literature up to June 6th 2025 was conducted to identify studies assessing the effects of ventilation strategies or hypoxemia-rescue therapies on physiological and clinical outcomes in adults supported by V-A ECMO or in animal V-A ECMO models. Because of anticipated heterogeneity across studies, we refrained from pooling of results. RESULTS: Out of 5,750 records screened, 12 studies met the inclusion criteria (10 clinical, 1 experimental, 1 computational). Four studies in humans observed that lower driving and peak inspiratory pressures, along with reduced respiratory rates, were associated with improved survival in V-A ECMO patients. One study found that moderate positive end-expiratory pressure (PEEP) conveyed protective effects on the lungs without compromising cardiac function, whereas excessive PEEP impaired systolic function without causing systemic hypotension. A computational study suggested that higher intrathoracic pressures may have cardioprotective effects by unloading the left ventricle and reducing myocardial oxygen demand. Very limited studies have explored adjunctive ventilation strategies, including inhaled nitric oxide and defined oxygenation targets during V-A ECMO, exhibiting at least a moderate risk of bias. CONCLUSIONS: Evidence on the effects of mechanical ventilation during V-A ECMO on cardiac function, recovery and clinical outcomes is limited, heterogeneous, and at considerable risk of bias. Well-designed mechanistic and interventional studies are needed to determine whether ventilation strategies can support myocardial recovery and facilitate successful V-A ECMO weaning.