Background:Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority. Objectives:To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs. Design:Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19. Setting:Contributed data were collected in clinical, community and research settings. Interventions:Interventions from original studies were included as covariates in models. Data sources:MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers. Methods:Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I2. Outcome measures:Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life. Results:PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality. Limitations:Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system. Conclusions:PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities. Future work:Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes. Study registration:This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578). Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132895) and is published in full in Health and Social Care Delivery Research; Vol. 14, No. 29. See the NIHR Funding and Awards website for further award information.

Encephalopathy is a common complication of sepsis, occurring in up to 70

BACKGROUND:International guidelines have emphasized the necessity of evaluating the temporal stability of acute respiratory distress syndrome (ARDS) subphenotypes. This study aimed to assess the temporal stability of subphenotypes of ARDS over 28 days. METHODS:A reanalysis of a randomized trial was conducted, including patients with COVID-19-related moderate-to-severe ARDS across 43 centers. A K-means clustering was conducted to identify subphenotypes at 7-day intervals from inclusion to day 28. A Bayesian discrete-time Markov model was constructed to assess the temporal stability of subphenotypes. RESULTS:Two subphenotypes were identified among 146 patients. At inclusion, 121 (83%) patients were in the hypoinflammatory subphenotype and 25 (17%) in the hyperinflammatory subphenotype. The hyperinflammatory subphenotype was associated with higher rates of organ failure, higher plasma levels of cytokines, chemokines, adhesion molecules, and proangiogenic factors, and lower endothelial stability than the hypoinflammatory subphenotype. The hyperinflammatory subphenotype was associated with higher 28-day mortality (13/25, 52% vs. 30/121, 25%, p = 0.001) and fewer ventilatory-free-days through day 28 (p < 0.01) than the hypoinflammatory subphenotype. In the Bayesian Markov model, over 7-day intervals, patients in the hypoinflammatory subphenotype had a higher probability of remaining hypoinflammatory (70%) or being extubated (17%) than of progressing to the hyperinflammatory subphenotype (7%). Inversely, patients in the hyperinflammatory subphenotype had a higher probability of remaining in the hyperinflammatory subphenotype (52%) or dying (23%) than of transitioning to the hypoinflammatory subphenotype (20%) or being extubated (5%). CONCLUSIONS:Inflammatory subphenotypes were stable in COVID-19-related ARDS, with few transitions over 28 days. Monitoring these subphenotypes could be valuable for assessing patient trajectories and treatment responses.

INTRODUCTION:The occurrence of sepsis in neurointensive care patients is linked to poor prognosis and high mortality. We hypothesized that an infection or sepsis (I/S) episode might increase the initial number of brain lesions and/or induce new brain lesions in neurointensive care patients. MATERIALS AND METHODS:This was a retrospective study between January 2015 and June 2020 that included neuroICU patients who had two magnetic resonance images and compared those who presented I/S episodes with those who did not. The two groups' differences were adjusted with propensity score matching. The main composite outcome was the increase in size of the initial brain lesion and/or the appearance of new brain lesions. RESULTS:A total of 150 neurointensive care patients were included, 50 with infection or sepsis (I/S) and 100 controls. New or worsened brain lesions were observed in 58.0% of the I/S group versus 35.0% of controls (adjusted odds ratio 8.08, 95% CI [3.28-11.29], p < 0.001). Lesions included ischemic strokes (44%), intraparenchymal hemorrhages (44%), and diffuse leukoencephalopathy (52%). Microbleeds were observed in 21.1% of I/S patients. I/S was associated with a longer ICU stay (median 23 vs. 10.5 days, p < 0.0001) and a higher rate of unfavorable outcome (mRS ≥ 4 at discharge: 40.0% vs. 12.0%, p = 0.003; at 1 year: 20.0% vs. 6.5%, p = 0.037). Results were similar in sensitivity analyses restricted to ventilated patients. CONCLUSION:The occurrence of I/S is associated with the extension of the initial lesion and/or the appearance of new brain lesions on MRI in patients hospitalized in the neurointensive care unit for primary brain injury.

Background Patients’ anxiety on intensive care unit (ICU) admission is associated with subsequent deterioration. Objective To assess whether patients’ fears/anxiety are predictive of new organ failure within 7 days of ICU admission. Methods In a prospective 3-center cohort study of non-comatose patients without delirium or invasive mechanical ventilation, 9 specific fears were evaluated through yes/no questions. Illness severity was assessed using the Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA). Intensity of acute and chronic anxiety was assessed with the state and trait components of the State-Trait Anxiety Inventory (STAI). Patients were followed up for 7 days. Results From April 2014 to December 2017, 373 patients (median [IQR] age, 63 [48-74] years; 152 [40.8%] women; median (IQR) SAPS II, 27 [19-37]) were included. Feelings of vulnerability and fear of dying were reported by 203 (54.4%) and 172 (46.1%) patients, respectively. The STAI-State score was 40 or greater in 192 patients (51.5%). Ninety-four patients (25.2%) had new organ failure. Feelings of vulnerability (odds ratio, 1.96 [95% CI, 1.12-3.43]; P=.02) and absence of fear of dying (odds ratio, 2.38 [95% CI, 1.37-4.17]; P=.002) were associated with new organ failure after adjustment for STAI-State score (≥40), SAPS II, and SOFA score. Conclusion Absence of fear of dying is associated with new organ failure within the first 7 days after ICU admission. Fear of dying may protect against subsequent deterioration by mobilizing patients’ homeostatic resources. ClinicalTrials.gov Identifier: NCT02355626

Critical illness is associated with long-term increased mortality and impaired quality of life (QoL). We assessed whether multidisciplinary consultations would improve outcome at 12 months (M12) after intensive care unit (ICU) discharge. We performed an open, multicenter, parallel-group, randomized clinical trial. Eligible are patients discharged alive from ICU in 11 French hospitals between 2012 and 2018. The intervention group had a multidisciplinary face-to-face consultation involving an intensivist, a psychologist, and a social worker at ICU discharge and then at M3 and M6 (optional). The control group had standard post-ICU follow-up. A consultation was scheduled at M12 for all patients. The QoL was assessed using the EuroQol-5 Dimensions-5 Level (Euro-QoL-5D-5L) which includes five dimensions (mobility, self-care, usual activities, pain, and anxiety/depression), each ranging from 1 to 5 (1: no, 2: slight, 3: moderate, 4: severe, and 5: extreme problems). The primary endpoint was poor clinical outcome defined as death or severe-to-extreme impairment of at least one EuroQoL-5D-5L dimension at M12. The information was collected by a blinded investigator by phone. Secondary outcomes were functional, psychological, and cognitive status at M12 consultation. 540 patients were included (standard, n = 272; multidisciplinary, n = 268). The risk for a poor outcome was significantly greater in the multidisciplinary group than in the standard group [adjusted odds ratio 1.49 (95

Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient’s age was 64 [42–76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3–10] days and the median total length of MV was 14 [10–23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.

Large language models (LLM) ability in natural language processing holds promise for diverse applications, yet their deployment in fields such as neurology faces domain-specific challenges. Hence, we introduce Neura: a scalable, explainable solution to specialize LLM. Blindly evaluated on a select set of five complex clinical cases compared to a cohort of 13 neurologists, Neura achieved normalized scores of 86.17% overall, 85% for differential diagnoses, and 88.24% for final diagnoses (55.11%, 46.15%, and 70.93% for neurologists) with rapid response times of 28.8 and 19 seconds (9 minutes and 37.2 seconds and 8 minutes and 51 seconds for neurologists) while consistently providing relevant, accurately cited information. These findings support the emerging role of LLM-driven applications to articulate human-acquired and integrated data with a vast corpus of knowledge, augmenting human experiential reasoning for clinical and research purposes.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study did not receive any funding.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.

BACKGROUND:Management of status epilepticus (SE) is focused on the early seizure termination. Refractory SE is an indication for sedation in patients with SE, but up to 75% of patients may be ventilated due to a neurological or respiratory failure. In patients requiring sedation, the clinical assessment is not sufficient to assess seizure control. Identifying those at risk of recurrent seizures could be useful to adapt their management. On the other hand, patients with low risk could benefit from an early withdrawal of sedation to avoid the impact of inappropriate sedation on outcome. OBJECTIVE:To determine the prevalence and the predictors of uncontrolled SE and its impact on outcome in patients with generalized convulsive SE (GCSE) requiring mechanical ventilation (MV). METHODS:We retrospectively included patients admitted to the intensive care unit with GCSE requiring MV. Uncontrolled SE was defined as persistent or recurrent seizures during sedation or within 24hours following withdrawal. A multivariable logistic regression model was used to assess the associated factors. RESULTS:Uncontrolled SE occurred in 37 out of 220 patients (17%). Persistent seizures at admission, higher SAPS II and central nervous system infection were associated with a higher risk of uncontrolled SE. Acute toxic or metabolic etiologies were associated with a decreased risk of uncontrolled SE. In a supplementary analysis, decrease of albumin blood levels was associated with uncontrolled SE. Uncontrolled SE was associated with a poor functional outcome and mortality at 90 days. CONCLUSIONS:Seventeen percent of patients with a GCSE requiring MV suffered from uncontrolled SE. Etiology and persistent seizures at admission were the main predictors of uncontrolled SE. Patients with uncontrolled SE had a longer duration of sedation and MV, a poor functional outcome and a higher mortality. Further studies are required to determine the impact of continuous electroencephalogram monitoring on the clinical course.

Abstract Background Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. Methods This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. Results A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes. Conclusions VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

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Every research project begins with a question. As its nature will influence all subsequent steps, including the methodology, the question should be clear and well-defined from the outset. This is therefore a major step in carrying out a research project, which requires expertise and work. It is indeed clinical experience and previous research that lead to a good question. For it to be relevant, it is necessary to master existing literature on the subject, to be open to new ideas, new techniques, new methodologies, imagination and creativity, as well as to pay attention to mentorship and expert advice. This question must meet criteria for feasibility, interest, novelty, ethics, and relevance (the FINER criteria). It should be formulated in a structured way to ensure maximum clarity, for example following the PICOT framework. Therefore, defining the main question of your clinical trial is not just a semantic exercise.

Tous les travaux de recherche commencent par une question. Cette question doit être claire et bien définie dès le départ, car sa nature influencera toutes les étapes suivantes, notamment la méthodologie. Il s’agit donc d’une étape majeure dans la réalisation d’un projet de recherche, qui demande de l’expertise et du travail. Une bonne question émerge en effet de l’expérience clinique et des recherches réalisées antérieurement. Elle nécessite pour être pertinente une maîtrise de la littérature existante sur le sujet, une ouverture à de nouvelles idées, de nouvelles techniques, de nouvelles méthodologies, de l’imagination et de la créativité, mais aussi une grande attention aux conseils de ses mentors et des experts établis. Cette question doit répondre à des critères de faisabilité, d’intérêt, de nouveauté, d’éthique et de pertinence (les critères FINER). Elle doit être formulée de manière structurée pour assurer un maximum de clarté, en suivant par exemple le cadre PICOT (pour population, intervention étudiée, contrôle, outcome et timeframe). Choisir et formuler la question principale de son essai clinique n’est donc pas un exercice purement sémantique.

While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., (i) the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; (ii) the importance of developing translational research from which therapeutic innovations can emerge; (iii) the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research.

In The Lancet Respiratory Medicine, Aurélien Mazeraud and colleagues showed that the application of intravenous immunoglobulins (IVIGs) in patients with COVID-19-induced moderate-to-severe acute respiratory distress syndrome did not improve clinical outcomes but had a non-significant association with more adverse events.1Mazeraud A Jamme M Mancusi RL et al.Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.Lancet Respir Med. 2022; 10: 158-166Summary Full Text Full Text PDF Scopus (24) Google Scholar We would like to address reasons for the lack of effect that were not discussed in Mazeraud and colleagues’ Article. The rationale to apply IVIGs in infectious diseases can be either to target hyperinflammation, to use the anti-infective properties of IVIGs to treat the primary infection, or both. Beyond that, IVIGs might provide protection against secondary infections and thereby reduce morbidity and mortality. First evidence shows that the beneficial effects of IVIGs might depend on the composition of the IVIG preparation, the immune status of the patient, and the severity of the disease.2Guell E Martín-Fernandez M De la Torre M et al.Impact of lymphocyte and neutrophil counts on mortality risk in severe community-acquired pneumonia with or without septic shock.J Clin Med. 2019; 8: 754Crossref Scopus (13) Google Scholar Concerning the preparation of the IVIG solution, those consisting mainly of IgG (as applied in Mazeraud and colleagues’ study) have been shown to have little or no effect in patients with sepsis.3Werdan K Pilz G Bujdoso O et al.Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study.Crit Care Med. 2007; 35: 2693-2701Crossref PubMed Scopus (167) Google Scholar, 4Brocklehurst P Farrell B King A et al.Treatment of neonatal sepsis with intravenous immune globulin.N Engl J Med. 2011; 365: 1201-1211Crossref PubMed Scopus (232) Google Scholar By contrast, first data published on IgM-enriched IVIG solution are encouraging.5Welte T Dellinger RP Ebelt H et al.Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).Intensive Care Med. 2018; 44: 438-448Crossref PubMed Scopus (77) Google Scholar, 6Gong S Ruprecht RM Immunoglobulin M: an ancient antiviral weapon—rediscovered.Front Immunol. 2020; 111943Crossref PubMed Scopus (26) Google Scholar Concerning the immune status of patients, Mazeraud and colleagues did not investigate parameters of immune function. Notably, in several studies, an increased mortality was associated with low baseline serum levels of immunoglobulins, as shown for instance for influenza.7Krautz C Maier SL Brunner M et al.Reduced circulating B cells and plasma IgM levels are associated with decreased survival in sepsis—a meta-analysis.J Crit Care. 2018; 45: 71-75Crossref PubMed Scopus (23) Google Scholar, 8Justel M Socias L Almansa R et al.IgM levels in plasma predict outcome in severe pandemic influenza.J Clin Virol. 2013; 58: 564-567Crossref PubMed Scopus (25) Google Scholar From a pathophysiological point of view, it would be possible that beneficial effects of a substitution of IVIGs were observed only in these patients, but not in those with normal or elevated baseline immunoglobulin levels. In this context, we would like to draw attention to a 2018 phase 2 randomised controlled trial in 160 patients with severe community-acquired pneumonia who required invasive mechanical ventilation.5Welte T Dellinger RP Ebelt H et al.Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).Intensive Care Med. 2018; 44: 438-448Crossref PubMed Scopus (77) Google Scholar In this double-blind study, in addition to standard of care, an IgM-enriched IVIG solution (42 mg IgM/kg per day) was applied. The primary combined endpoint of ventilator-free days and 28-day all-cause mortality was not statistically different in the intention-to-treat cohort (22·2% vs 27·8%). Most importantly, in a prespecified subgroup analysis of patients with a high level of inflammation (C-reactive protein concentrations higher than 70 mg/L), low IgM serum levels (lower than 0·8 g/L) or both, mortality was reduced significantly, with the highest level of mortality reduction in the cohort with high C-reactive protein concentrations and low IgM levels. Therefore, by contrast with the conclusion of Mazeraud and colleagues, we hypothesise that IVIG application in patients with COVID-19 might be beneficial if a specific IgM-enriched IVIG solution is applied in patients with low IgM levels and a high level of inflammation. DKM received lecture honoraria from Biotest. All other authors declare no competing interests. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trialIn patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. Full-Text PDF Why the application of IVIG might be beneficial in patients with COVID-19 – Authors' replyWe thank Detlef Kindgen-Milles and colleagues for their Correspondence regarding the administration of intravenous immunoglobulin (IVIG) solutions enriched with IgM rather than solutions containing mainly IgG in patients with severe COVID-19. Full-Text PDF

Background Critically ill patients are at risk of developing a postintensive care syndrome (PICS), which is characterized by physical, psychological, and cognitive impairments and which dramatically impacts the patient’s quality of life (QoL). No intervention has been shown to improve QoL. We hypothesized that a medical, psychological, and social follow-up would improve QoL by mitigating the PICS. Objective This multicenter, randomized controlled trial (SUIVI-REA) aims to compare a multidisciplinary follow-up with a standard postintensive care unit (ICU) follow-up. Methods Patients were randomized to the control or intervention arm. In the intervention arm, multidisciplinary follow-up involved medical, psychological, and social evaluation at ICU discharge and at 3, 6, and 12 months thereafter. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. Baseline characteristics at ICU discharge were collected for all patients. The primary outcome was QoL at 1 year, assessed using the Euro Quality of Life-5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological, and functional status; social and professional reintegration; and the rate of rehospitalization and outpatient consultations at 1 year. Results The study was funded by the Ministry of Health in June 2010. It was approved by the Ethics Committee on July 8, 2011. The first and last patient were randomized on December 20, 2012, and September 1, 2017, respectively. A total of 546 patients were enrolled across 11 ICUs. At present, data management is ongoing, and all parties involved in the trial remain blinded. Conclusions The SUVI-REA multicenter randomized controlled trial aims to assess whether a post-ICU multidisciplinary follow-up improves QoL at 1 year. Trial Registration Clinicaltrials.gov NCT01796509; https://clinicaltrials.gov/ct2/show/NCT01796509 International Registered Report Identifier (IRRID) DERR1-10.2196/30496

Despite recent therapeutic advances, ischemic stroke is still a leading cause of death and disability. There is renewed attention on peripheral inflammatory signaling as a way of modulating the post-ischemic neuro-inflammatory process. The immune-brain crosstalk has long been the focus for understanding the mechanisms of sickness behavior, which is an adaptive autonomic, neuroendocrine, and behavioral response to a peripheral inflammation. It is mediated by humoral and neural pathways that mainly involve the circumventricular organs and vagal nerve, respectively. In this review we address the question of how sepsis and stroke can dysregulate this adaptive response, notably by impairing the central integration of peripheral signaling, but also by efferent control of the immune response. We highlight the potential role of gut–brain and brain–spleen signaling in stroke.