Development and validation of a community acquired sepsis-worsening score in the adult emergency department: a prospective cohort: the CASC score.

BACKGROUND: Sepsis is a leading cause of death and serious illness that requires early recognition and therapeutic management to improve survival. The quick-SOFA score helps in its recognition, but its diagnostic performance is insufficient. To develop a score that can rapidly identify a community acquired septic situation at risk of clinical complications in patients consulting the emergency department (ED). METHODS: We conducted a monocentric, prospective cohort study in the emergency department of a university hospital between March 2016 and August 2018 (NCT03280992). All patients admitted to the emergency department for a suspicion of a community-acquired infection were included. Predictor variables of progression to septic shock or death within the first 90 days were selected using backward stepwise multivariable logistic regression to develop a clinical score. Receiver operating characteristic (ROC) curves were constructed to determine the discriminating power of the area under the curve (AUC). We also determined the threshold of our score that optimized the performance required for a sepsis-worsening score. We have compared our score with the NEWS-2 and qSOFA scores. RESULTS: Among the 21,826 patients admitted to the ED, 796 patients were suspected of having community-acquired infection and 461 met the sepsis criteria; therefore, these patients were included in the analysis. The median [interquartile range] age was 72 [54-84] years, 248 (54%) were males, and 244 (53%) had respiratory symptoms. The clinical score ranged from 0 to 90 and included 8 variables with an area under the ROC curve of 0.85 (confidence interval [CI] 95% 0.81-0.89). A cut-off of 26 yields a sensitivity of 88% (CI 95% 0.79-0.93), a specificity of 62% (CI 95% 57-67), and a negative predictive value of 95% (CI 95% 91-97). The area under the ROC curve for our score was 0.85 (95% CI, 0.81-0.89) versus 0.73 (95% CI, 0.68-0.78) for qSOFA and 0.66 (95% CI, 0.60-0.72) for NEWS-2. CONCLUSIONS: Our study provides an accurate clinical score for identifying septic patients consulting the ED early at risk of worsening disease. This score could be implemented at admission.

Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a ß-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). METHODS: We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a ß-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. RESULTS: Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. CONCLUSION: Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.

BACKGROUND: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients. METHODS: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6). RESULTS: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected. CONCLUSION: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Acquired agitation in acute respiratory distress syndrome with COVID-19 compared to influenza patients: a propensity score matching observational study.

BACKGROUND: A growing body of evidence reports that agitation and encephalopathy are frequent in critically ill Covid-19 patients. We aimed to assess agitation's incidence and risk factors in critically ill ARDS patients with Covid-19. For that purpose, we compared SARS-CoV-2 acute respiratory distress syndrome (ARDS) patients with a population of influenza ARDS patients, given that the influenza virus is also known for its neurotropism and ability to induce encephalopathy. METHODS: We included all the patients with laboratory-confirmed Covid-19 infection and ARDS admitted to our medical intensive care unit (ICU) between March 10th, 2020 and April 16th, 2021, and all the patients with laboratory-confirmed influenza infection and ARDS admitted to our ICU between April 10th, 2006 and February 8th, 2020. Clinical and biological data were prospectively collected and retrospectively analyzed. We also recorded previously known factors associated with agitation (ICU length of stay, length of invasive ventilation, SOFA score and SAPS II at admission, sedative and opioids consumption, time to defecation). Agitation was defined as a day with Richmond Agitation Sedation Scale greater than 0 after exclusion of other causes of delirium and pain. We compared the prevalence of agitation among Covid-19 patients during their ICU stay and in those with influenza patients. RESULTS: We included 241 patients (median age 62 years [53-70], 158 males (65.5%)), including 146 patients with Covid-19 and 95 patients with Influenza. One hundred eleven (46.1%) patients had agitation during their ICU stay. Patients with Covid-19 had significantly more agitation than patients with influenza (respectively 80 patients (54.8%) and 31 patients (32.6%), p < 0.01). After matching with a propensity score, Covid-19 patients remained more agitated than influenza patients (49 (51.6% vs 32 (33.7%), p = 0.006). Agitation remained independently associated with mortality after adjustment for other factors (HR = 1.85, 95% CI 1.37-2.49, p < 0.001). CONCLUSION: Agitation in ARDS Covid-19 patients was more frequent than in ARDS influenza patients and was not associated with common risk factors, such as severity of illness or sedation. Systemic hyperinflammation might be responsible for these neurological manifestations, but there is no specific management to our knowledge.

Carbofuran self-poisoning: forensic and analytic investigations in twins and literature review.

Carbofuran is a pesticide widely used in agricultural context to kill insects, mites, and flies by ingestion or contact. Along with literature review, we aimed to (i) present the clinical, autopsy, and toxicological findings of carbofuran self-poisonings in two 69-year-old twins, resulting in the death of one of them and (ii) assess carbofuran metabolite distribution using molecular networking. Quantitative analysis of carbofuran and its main metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) was carried out using an original liquid chromatography-tandem mass spectrometry method on biological samples (cardiac or peripheral blood, urine, bile, and gastric contents). Toxicological analysis of post-mortem samples (twin 1) highlighted high concentrations of carbofuran and its metabolites in cardiac blood, bile, and gastric contents. These compounds were also quantified in blood and/or urine samples of the living brother (twin 2), confirming poisoning. Using molecular networking approach to facilitate visualization of mass spectrometry datasets and sample-to-sample comparisons, we detected two more metabolites (7-phenol-carbofuran and 3-hydroxycarbofuran glucuronide) in bile (twin 1) and urine (twin 2). These results highlight the value of (i) these compounds as carbofuran consumption markers and (ii) bile samples in post-mortem analysis to confirm poisoning. From an analytical point of view, molecular networking allowed the detection and interpretation of carbofuran metabolite ammonium adducts which helped to confirm their identification annotations, as well as their structural data. From a clinical point of view, the different outcomes between the two brothers are discussed. Overall, these cases provide novel information regarding the distribution of carbofuran and its metabolites in poisoning context.

Tolerance and complications of therapeutic plasma exchange by centrifugation: A single center experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) constitutes an important therapy for hematological, neurological, immunological, and nephrological diseases. Most studies have focused on efficacy, whereas tolerance and complications during sessions have been less well studied and not recently. MATERIAL AND METHODS: We conducted a single center retrospective study of all patients who underwent TPE between 2011 and 2018. TPE sessions using the centrifugation technique were performed by dedicated trained nurses. Specific side effects were identified through surveillance forms completed contemporaneously. The primary outcome was the rate of all-type adverse effects that occurred during the TPE sessions. RESULTS: In total, 1895 TPE sessions performed on 185 patients were analyzed. At least one adverse effect was reported for 805 sessions (42.5% [29.9%-70.1%]), corresponding to 171 patients (92.4% [87.6%-95.8%]). Hypotension occurred during 288 sessions (15.2%), was asymptomatic in 95.8% of cases, and more frequent with the use of 4% albumin than fresh frozen plasma (FFP) (19.8 vs 8.9%, P <.0001). Hypocalcemia occurred during 370 sessions (19.6%) and was more frequent with the use of FFP than with the use of albumin alone (FFP alone: 28.0%, albumin + FFP: 26%, albumin alone: 11.7%; P <.0001). Allergic reactions occurred during 56 sessions (3%), exclusively with FFP. Severe adverse effects were reported for 0.3% of sessions and 5.4% of patients. CONCLUSIONS: TPE is a safe therapy when performed by a trained team. Adverse effects were frequent but mostly not serious. The replacement fluid was the main determinant of the occurrence of complications. (ClinicalTrials.gov ID: NCT03888417).

SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.

PURPOSE: The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. METHODS: A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. RESULTS: We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. CONCLUSIONS: The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.

Venoarterial extracorporeal membrane oxygenation induces early immune alterations.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides heart mechanical support in critically ill patients with cardiogenic shock. Despite important progresses in the management of patients under VA-ECMO, acquired infections remain extremely frequent and increase mortality rate. Since immune dysfunctions have been described in both critically ill patients and after surgery with cardiopulmonary bypass, VA-ECMO initiation may be responsible for immune alterations that may expose patients to nosocomial infections (NI). Therefore, in this prospective study, we aimed to study immune alterations induced within the first days by VA-ECMO initiation. METHODS: We studied immune alterations induced by VA-ECMO initiation using cytometry analysis to characterize immune cell changes and enzyme-linked immunosorbent assay (ELISA) to explore plasma cytokine levels. To analyze specific changes induced by VA-ECMO initiation, nine patients under VA-ECMO (VA-ECMO patients) were compared to nine patients with cardiogenic shock (control patients). RESULTS: Baseline immune parameters were similar between the two groups. VA-ECMO was associated with a significant increase in circulating immature neutrophils with a significant decrease in C5a receptor expression. Furthermore, we found that VA-ECMO initiation was followed by lymphocyte dysfunction along with myeloid-derived suppressor cells (MDSC) expansion. ELISA analysis revealed that VA-ECMO initiation was followed by an increase in pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α along with IL-10, a highly immunosuppressive cytokine. CONCLUSION: VA-ECMO is associated with early immune changes that may be responsible for innate and adaptive immune alterations that could confer an increased risk of infection.

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). Objective: To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. Design, Settings, and Participants: This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Interventions: Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. Main Outcomes and Measures: The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Results: Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Conclusions and Relevance: Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT02723383.

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.

Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia.

BACKGROUND: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). METHODS: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. RESULTS: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. CONCLUSIONS: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.

At-Risk Drinking Is Independently Associated With Acute Kidney Injury in Critically Ill Patients.

OBJECTIVES: Unhealthy use of alcohol and acute kidney injury are major public health problems, but little is known about the impact of excessive alcohol consumption on kidney function in critically ill patients. We aimed to determine whether at-risk drinking is independently associated with acute kidney injury in the ICU and at ICU discharge. DESIGN: Prospective observational cohort study. SETTING: A 21-bed polyvalent ICU in a university hospital. PATIENTS: A total of 1,107 adult patients admitted over a 30-month period who had an ICU stay of greater than or equal to 3 days and in whom alcohol consumption could be assessed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed Kidney Disease Improving Global Outcomes stages 2-3 acute kidney injury in 320 at-risk drinkers (29%) and 787 non-at-risk drinkers (71%) at admission to the ICU, within 4 days after admission and at ICU discharge. The proportion of patients with stages 2-3 acute kidney injury at admission to the ICU (42.5% vs 18%; p < 0.0001) was significantly higher in at-risk drinkers than in non-at-risk drinkers. Within 4 days and after adjustment on susceptible and predisposing factors for acute kidney injury was performed, at-risk drinking was significantly associated with acute kidney injury for the entire population (odds ratio, 2.15; 1.60-2.89; p < 0.0001) in the subgroup of 832 patients without stages 2-3 acute kidney injury at admission to the ICU (odds ratio, 1.44; 1.02-2.02; p = 0.04) and in the subgroup of 971 patients without known chronic kidney disease (odds ratio, 1.92; 1.41-2.61; p < 0.0001). Among survivors, 22% of at-risk drinkers and 9% of non-at-risk drinkers were discharged with stages 2-3 acute kidney injury (p < 0.001). CONCLUSIONS: Our results suggest that chronic and current alcohol misuse in critically ill patients is associated with kidney dysfunction. The systematic and accurate identification of patients with alcohol misuse may allow for the prevention of acute kidney injury.

Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial.

Importance: High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. Objective: To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and Participants: Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. Interventions: Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation. Main Outcomes and Measures: The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. Results: Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P = .25). Conclusions and Relevance: In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial Registration: ClinicalTrials.gov Identifier: NCT03121482.

Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity.

ABSTRACT: International guidelines regarding the management of immune effector cell-associated neurotoxicity syndrome (ICANS) recommend several diagnostic investigations, including magnetic resonance imaging (MRI), lumbar puncture (LP), and electroencephalogram (EEG) based on ICANS grade. However, the impact of these investigations has not yet been evaluated. Here, we aimed to describe the role of MRI, LP, and EEG in the management of ICANS in a cohort of real-life patients treated with chimeric antigen receptor (CAR) T cells at the University Hospital of Rennes, France. Between August 2018 and January 2023, a total of 190 consecutive patients were treated with CAR T cells. Among those, 91 (48%) developed ICANS. MRI was performed in 71 patients (78%) with ICANS, with a therapeutic impact in 4% of patients, despite frequent abnormal findings. LP was performed in 43 patients (47%), which led to preemptive antimicrobial agents in 7% of patients, although no infection was eventually detected. Systematic EEG was performed in 51 patients (56%), which led to therapeutic modifications in 16% of patients. Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, whereas MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines but question the need for systematic MRI and LP, which might be left to the discretion of the treating physician.

A case report of Covid-19 in an autoimmune pulmonary alveolar proteinosis: An association in tune with the times!

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the alveoli accumulation of surfactants proteins and lipids, which diagnosis is confirmed by the presence of GM-CSF antibodies in serum. PAP can be evoked when its characteristic images on chest computed-tomography (CT) are present: bilateral and multifocal ground-glass opacities and crazy-paving appearance. Patients with PAP are at an increased risk of opportunistic infections caused by Nocardia, mycobacteria and fungal pathogens due to impaired processing of pulmonary surfactant. We here report a typical case of newly diagnosed autoimmune PAP, with initial indication to realize a whole-lung lavage. Despite this treatment the patient presented a marked clinical worsening, with increasing need for oxygen and finally the need for mechanical ventilation. The chest CT was controlled and found to be typical of PAP, while the search for opportunistic infections remained negative. Finally, SARS-CoV-2 PCR was performed on bronchoalveolar lavage fluid, and was positive, whereas it had previously been negative twice. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. We believe that a SARS-CoV-2 RT-PCR should be systematically realized in case of respiratory deterioration in PAP patients.

Impact of Arterial CO2 Retention in Patients With Moderate or Severe ARDS.

BACKGROUND: Lung-protective ventilation (reduced tidal volume and limited plateau pressure) may lead to CO2 retention. Data about the impact of hypercapnia in patients with ARDS are scarce and conflicting. METHODS: We performed a non-interventional cohort study with subjects with ARDS admitted from 2006 to 2021 and with PaO2 /FIO2 ≤ 150 mm Hg. We examined the association between severe hypercapnia (PaCO2 ≥ 50 mm Hg) on the first 5 days after the diagnosis of ARDS and death in ICU for 930 subjects. All the subjects received lung-protective ventilation. RESULTS: Severe hypercapnia was noted in 552 subjects (59%) on the first day of ARDS (day 1); 323/930 (34.7%) died in the ICU. Severe hypercapnia on day 1 was associated with mortality in the unadjusted (odds ratio 1.54, 95% CI 1.16-1.63; P = .003) and adjusted (odds ratio 1.47, 95% CI 1.08-2.43; P = .004) models. In the Bayesian analysis, the posterior probability that severe hypercapnia was associated with ICU death was > 90% in 4 different priors, including a septic prior for this association. Sustained severe hypercapnia on day 5, defined as severe hypercapnia present from day 1 to day 5, was noted in 93 subjects (12%). After propensity score matching, severe hypercapnia on day 5 remained associated with ICU mortality (odds ratio 1.73, 95% CI 1.02-2.97; P = .047). CONCLUSIONS: Severe hypercapnia was associated with mortality in subjects with ARDS who received lung-protective ventilation. Our results deserve further evaluation of the strategies and treatments that aim to control CO2 retention.

Bacterial and fungal infections: a frequent and deadly complication among critically ill acute liver failure patients.

BACKGROUND: Acute liver failure (ALF) is a rare but life-threatening condition mostly requiring intensive care unit (ICU) admission. ALF induces immune disorders and may promote infection acquisition. However, the clinical spectrum and impact on patients' prognosis remain poorly explored. METHODS: We conducted a retrospective single-centre study on patients admitted for ALF to the ICU of a referral University Hospital from 2000 to 2021. Baseline characteristics and outcomes according to the presence of infection until day 28 were analysed. Risk factors for infection were determined using logistic regression. The impact of infection on 28-day survival was assessed using the proportional hazard Cox model. RESULTS: Of the 194 patients enrolled, 79 (40.7%) underwent infection: community-acquired, hospital-acquired before ICU and ICU-acquired before/without and after transplant in 26, 23, 23 and 14 patients, respectively. Most infections were pneumonia (41.4%) and bloodstream infection (38.8%). Of a total of 130 microorganisms identified, 55 were Gram-negative bacilli (42.3%), 48 Gram-positive cocci (36.9%) and 21 were fungi (16.2%). Obesity (OR 3.77 [95% CI 1.18-14.40]; p = .03) and initial mechanical ventilation (OR 2.26 [95% CI 1.25-4.12]; p = .007) were independent factors associated with overall infection. SAPSII > 37 (OR 3.67 [95% CI 1.82-7.76], p < .001) and paracetamol aetiology (OR 2.10 [95% CI 1.06-4.22], p = .03) were independently associated with infection at admission to ICU. On the opposite, paracetamol aetiology was associated with lower risk of ICU-acquired infection (OR 0.37 [95% CI 0.16-0.81], p = .02). Patients with any type of infection had lower day 28 survival rates (57% versus 73%; HR 1.65 [1.01-2.68], p = .04). The presence of infection at ICU admission (p = .04), but not ICU-acquired infection, was associated with decreased survival. CONCLUSIONS: The prevalence of infection is high in ALF patients which is associated with a higher risk of death. Further studies assessing the use of early antimicrobial therapy are needed.

Moderate-to-severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality.

Background: This study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and influenza ARDS patients with arterial oxygen tension (P aO2 )/inspiratory oxygen fraction (F IO2 ) ≤150 mmHg. Methods: We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (C rs), ventilator ratio, corrected minute ventilation (V'Ecorr) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed. Results: On day 1 of ARDS, COVID-19 patients had significantly higher P aO2 /F IO2 (median (interquartile range) 97 (79-129.2) versus 83 (62.2-114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0-16.0) versus 14.0 (12.0-16.7) cmH2O; p=0.01), ventilatory ratio (2.08 (1.73-2.49 versus 2.52 (1.97-3.03); p<0.001), V'Ecorr (12.7 (10.2-14.9) versus 14.9 (11.6-18.6) L·min-1; p<0.001) and index (80 (70-89) versus 84 (75-94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values of P aO2 /F IO2 , arterial carbon dioxide tension, ventilatory ratio and V'Ecorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29% versus 21.7%; p=0.43). Conclusions: Ventilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.