Central role of the ramAR locus in the multidrug resistance in ESBL-Enterobacterales.

The aim of this study was to evaluate the proportion of resistance to a temocillin, tigecycline, ciprofloxacin, and chloramphenicol phenotype called t2c2 that resulted from mutations within the ramAR locus among extended-spectrum ß-lactamases-Enterobacterales (ESBL-E) isolated in three intensive care units for 3 years in a French university hospital. Two parallel approaches were performed on all 443 ESBL-E included: (i) the minimal inhibitory concentrations of temocillin, tigecycline, ciprofloxacin, and chloramphenicol were determined and (ii) the genomes obtained from the Illumina sequencing platform were analyzed to determine multilocus sequence types, resistomes, and diversity of several tetR-associated genes including ramAR operon. Among the 443 ESBL-E strains included, isolates of Escherichia coli (n = 194), Klebsiella pneumoniae (n = 122), and Enterobacter cloacae complex (Ecc) (n = 127) were found. Thirty-one ESBL-E strains (7%), 16 K. pneumoniae (13.1%), and 15 Ecc (11.8%) presented the t2c2 phenotype in addition to their ESBL profile, whereas no E. coli presented these resistances. The t2c2 phenotype was invariably reversible by the addition of Phe-Arg-ß-naphthylamide, indicating a role of resistance-nodulation-division pumps in these observations. Mutations associated with the t2c2 phenotype were restricted to RamR, the ramAR intergenic region (IR), and AcrR. Mutations in RamR consisted of C- or N-terminal deletions and amino acid substitutions inside its DNA-binding domain or within key sites of protein-substrate interactions. The ramAR IR showed nucleotide substitutions involved in the RamR DNA-binding domain. This diversity of sequences suggested that RamR and the ramAR IR represent major genetic events for bacterial antimicrobial resistance.IMPORTANCEMorbimortality caused by infectious diseases is very high among patients hospitalized in intensive care units (ICUs). A part of these outcomes can be explained by antibiotic resistance, which delays the appropriate therapy. The transferable antibiotic resistance gene is a well-known mechanism to explain the high rate of multidrug resistance (MDR) bacteria in ICUs. This study describes the prevalence of chromosomal mutations, which led to additional antibiotic resistance among MDR bacteria. More than 12% of Klebsiella pneumoniae and Enterobacter cloacae complex strains presented mutations within the ramAR locus associated with a dysregulation of an efflux pump called AcrAB-TolC and a porin: OmpF. These dysregulations led to an increase in antibiotic output notably tigecycline, ciprofloxacin, and chloramphenicol associated with a decrease of input for beta-lactam, especially temocillin. Mutations within transcriptional regulators such as ramAR locus played a major role in antibiotic resistance dissemination and need to be further explored.

Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

Evaluation of ChatGPT in Predicting 6-Month Outcomes After Traumatic Brain Injury.

OBJECTIVES: To evaluate the capacity of ChatGPT, a widely accessible and uniquely popular artificial intelligence-based chatbot, in predicting the 6-month outcome following moderate-to-severe traumatic brain injury (TBI). DESIGN: Single-center observational retrospective study. SETTING: Data are from a neuro-ICU from a level 1 trauma center. PATIENTS: All TBI patients admitted to ICU between September 2021 and October 2022 were included in a prospective database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on anonymized clinical, imaging, and biological information available at the patients' hospital admission and extracted from the database, clinical vignettes were retrospectively submitted to ChatGPT for prediction of patients' outcomes. The predictions of two intensivists (one neurointensivist and one non-neurointensivist) both from another level 1 trauma center (Beaujon Hospital), were also collected as was the International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) scoring. Each intensivist, as well as ChatGPT, made their prognostic evaluations independently, without knowledge of the others' predictions and of the patients' actual management and outcome. Both the intensivists and ChatGPT were given access to the exact same set of information. The main outcome was a 6-month-functional status dichotomized into favorable (Glasgow Outcome Scale Extended [GOSE] ≥ 5) versus poor (GOSE < 5). Prediction of intracranial hypertension management, pulmonary infectious risk, and removal of life-sustaining therapies was also investigated as secondary outcomes. Eighty consecutive moderate-to-severe TBI patients were included. For the 6-month outcome prognosis, area under the receiver operating characteristic curve (AUC-ROC) for ChatGPT, the neurointensivist, the non-neurointensivist, and IMPACT were, respectively, 0.62 (0.50-0.74), 0.70 (0.59-0.82), 0.71 (0.59-0.82), and 0.81 (0.72-0.91). ChatGPT had the highest sensitivity (100%), but the lowest specificity (26%). For secondary outcomes, ChatGPT's prognoses were generally less accurate than clinicians' prognoses, with lower AUC values for most outcomes. CONCLUSIONS: This study does not support the use of ChatGPT for prediction of outcomes after TBI.

N-Acetylcysteine to Reduce Mortality for Patients Requiring Cardiac Catheterization or Cardiac Surgery: A Systematic Review and Meta-analysis.

ABSTRACT: Multimers of von Willebrand factor play a critical role in various processes inducing morbidity and mortality in cardiovascular-risk patients. With the ability to reduce von Willebrand factor multimers, N-acetylcysteine (NAC) could reduce mortality in patients undergoing coronary catheterization or cardiac surgery. However, its impact in perioperative period has never been studied so far in regard of its potential cardiovascular benefits. Then, 4 databases were searched for randomized controlled trials that compared in-hospital mortality between an experimental group, with NAC, and a control group without NAC, in patients undergoing coronary catheterization or cardiac surgery. The primary efficacy outcome was in-hospital mortality. Secondary outcomes were the occurrence of thrombotic events, major cardiovascular events, myocardial infarction, and contrast-induced nephropathy. The safety outcome was occurrence of hemorrhagic events. Nineteen studies totaling 3718 patients were included. Pooled analysis demonstrated a reduction of in-hospital mortality associated with NAC: odds ratio, 0.60; 95% confidence interval, 0.39-0.92; P = 0.02. The occurrence of secondary outcomes was not significantly reduced with NAC except for contrast-induced nephropathy. No difference was reported for hemorrhagic events. Subgroup analyses revealed a life-saving effect of NAC in a dose-dependent manner with reduction of in-hospital mortality for the NAC high-dose group, but not for the NAC standard-dose (<3500-mg) group. In conclusion, without being able to conclude on the nature of the mechanism involved, our review suggests a benefit of NAC in cardiovascular-risk patients in perioperative period in terms of mortality and supports prospective confirmatory studies.

Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.

BACKGROUND: Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. METHODS: We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. FINDINGS: Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. INTERPRETATION: After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. FUNDING: The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.

Impact of early external ventricular drainage on functional outcome after traumatic brain injury: a bicentric retrospective cohort analysis.

PURPOSE: Several studies have confirmed that external ventricular drain decreases intracranial pressure (ICP) after traumatic brain injury (TBI). Considering its impact on ICP control and cerebral waste metabolites clearance, timing of external ventricular drain (EVD) insertion could improve CSF drainage efficiency. The aim of the study was to evaluate the impact of early EVD versus a later one on the 3-month outcome. METHODS: For this retrospective cohort study conducted in two regional trauma-center (Caen CHU Côte de Nacre and Beaujon Hospital) between May 2011 and March 2019, all patients with intracranial hypertension following TBI and treated with EVD were included. We defined the early EVD by drainage within the 24 h of the hospital admission and the late EVD insertion by drainage beyond 24 h. A poor outcome was defined as a Glasgow Outcome Scale of one or two at 3 months. RESULTS: Among the cohort of 671 patients, we analyzed 127 patients. Sixty-one (48.0%) patients had an early insertion of EVD. In the early EVD group, the mean time to insertion was 10 h versus 55 h in the late EVD group. Among the analyzed patients, 69 (54.3%) had a poor outcome including 39 (63.9%) in the early group and 30 (45.5%) in the later one. After adjustment on prognostic factors, early EVD insertion was not associated with a decrease in a poor outcome at 3-months (OR = 1.80 [0.73-4.53]). CONCLUSION: Early insertion of EVD (<24 h) for intracranial hypertension after TBI was not associated with improved outcome at 3 months.

Continuous and deep sedation until death after a decision to withdraw life-sustaining therapies in intensive care units: A national survey.

BACKGROUND: Continuous and deep sedation until death is a much highly debated end-of-life practice. France is unique in having a regulatory framework for it. However, there are no data on its practice in intensive care units (ICUs). AIM: The aim is to describe continuous and deep sedation in relation to the framework in the specific context of withdrawal of life-sustaining therapies in ICUs, that is, its decision-making process and its practice compared to other end-of-life practices in this setting. DESIGN AND SETTING: French multicenter observational study. Consecutive ICU patients who died after a decision to withdraw life-sustaining therapies. RESULTS: A total of 343 patients in 57 ICUs, 208 (60%) with continuous and deep sedation. A formalized procedure for continuous and deep sedation was available in 32% of the ICUs. Continuous and deep sedation was not the result of a collegial decision-making process in 17% of cases, and did not involve consultation with an external physician in 29% of cases. The most commonly used sedative medicines were midazolam (10 [5-18] mg h-1) and propofol (200 [120-250] mg h -1). The Richmond Agitation Sedation Scale (RASS) was -5 in 60% of cases. Analgesia was associated with sedation in 94% of cases. Compared with other end-of-life sedative practices (n = 98), medicines doses were higher with no difference in the depth of sedation. CONCLUSIONS: This study shows a poor compliance with the framework for continuous and deep sedation. It highlights the need to formalize it to improve the decision-making process and the match between the intent, the practice and the actual effect.

Consequences of General Anesthesia in Infancy on Behavior and Brain Structure.

BACKGROUND: One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes. METHODS: A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy. RESULTS: The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure. CONCLUSIONS: The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.

Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Is There a Relevant Experimental Model? A Systematic Review of Preclinical Literature.

Delayed cerebral ischemia (DCI) is one of the main prognosis factors for disability after aneurysmal subarachnoid hemorrhage (SAH). The lack of a consensual definition for DCI had limited investigation and care in human until 2010, when a multidisciplinary research expert group proposed to define DCI as the occurrence of cerebral infarction (identified on imaging or histology) associated with clinical deterioration. We performed a systematic review to assess whether preclinical models of SAH meet this definition, focusing on the combination of noninvasive imaging and neurological deficits. To this aim, we searched in PUBMED database and included all rodent SAH models that considered cerebral ischemia and/or neurological outcome and/or vasospasm. Seventy-eight publications were included. Eight different methods were performed to induce SAH, with blood injection in the cisterna magna being the most widely used (n = 39, 50%). Vasospasm was the most investigated SAH-related complication (n = 52, 67%) compared to cerebral ischemia (n = 30, 38%), which was never investigated with imaging. Neurological deficits were also explored (n = 19, 24%). This systematic review shows that no preclinical SAH model meets the 2010 clinical definition of DCI, highlighting the inconsistencies between preclinical and clinical standards. In order to enhance research and favor translation to humans, pertinent SAH animal models reproducing DCI are urgently needed.

Effect of patient-controlled epidural analgesia with and without automatic intermittent bolus on levobupivacaine consumption during labour: A single-centre prospective double-blinded randomised controlled study.

BACKGROUND: During labour, the effects of adding a programmed intermittent epidural bolus (PIEB) baseline analgesic regimen to patient-controlled epidural analgesia (PCEA) remain uncertain. METHODS: This single centre prospective double-blinded controlled study randomised nulliparous women over 35 weeks of gestational age in a PCEA + PIEB or PCEA only group. After an epidural analgesia catheter was inserted, a specific pump administered a solution of levobupivacaine 0.625 mg mL-1, sufentanil 0.25 µg mL-1, and clonidine 0.375 µg mL-1. In both groups the PCEA mode delivered an 8 mL bolus with a lockout period of 8 min. In the PCEA + PIEB group, women also received a programmed 8 mL bolus every 60 min. Additional bolus were allowed if required. The primary outcome was the hourly consumption of levobupivacaine from epidural catheter placement to new-born delivery. Secondary outcome were motor block, oxytocin use, sufentanil consumption, additional bolus required, instrumental vaginal delivery, unplanned caesarean section, pain during labour and women's satisfaction. RESULTS: Analysis included 162 and 155 women in the PCEA and PCEA + PIEB groups, respectively. The median [IQR] hourly consumption of levobupivacaine was significantly lower in the PCEA group (9.9 (7.8-12.4] mg h-1) as compared to the PCEA + PIEB group (11.2 [7.9-14.3] mg h-1; p = 0.046). The difference between medians was 1.3 mg h-1 95 % CI (0.1-2.9). There was no difference between groups for secondary outcomes. CONCLUSIONS: PCEA only modestly decreased the hourly consumption of local anaesthetic as compared to PCEA + PIEB but the difference was not clinically relevant.

Decreased number of deaths related to severe traumatic brain injury in intensive care unit during the first lockdown in Normandy: at least one positive side effect of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has led to severe containment measures to protect the population in France. The first lockdown modified daily living and could have led to a decrease in the frequency of severe traumatic brain injury (TBI). In the present study, we compared the frequency and severity of severe TBI before and during the first containment in Normandy. METHODS: We included all patients admitted in the intensive care unit (ICU) for severe TBI in the two tertiary neurosurgical trauma centres of Normandy during the first lockdown. The year before the containment served as control. The primary outcome was the number of patients admitted per week in ICU. We compared the demographic characteristics, TBI mechanisms, CT scan, surgical procedure, and mortality rate. RESULTS: The incidence of admissions for severe TBI in Normandy decreased by 33% during the containment. The aetiology of TBI significantly changed during the containment: there were less traffic road accidents and more TBI related to alcohol consumption. Patients with severe TBI during the containment had a better prognosis according to the impact score (p=0.04). We observed a significant decrease in the rate of short-term mortality related to severe TBI during the period of lockdown (p=0.02). CONCLUSIONS: Containment related to the COVID-19 pandemic has resulted in a modification of the mechanisms of severe TBI in Normandy, which was associated with a decline in the rate of short-term death in intensive unit care.

Impact of the SARS-COV-2 outbreak on epidemiology and management of major traumain France: a registry-based study (the COVITRAUMA study).

BACKGROUND: Emerging evidence suggests that the reallocation of health care resources during the COVID-19 pandemic negatively impacts health care system. This study describes the epidemiology and the outcome of major trauma patients admitted to centers in France during the first wave of the COVID-19 outbreak. METHODS: This retrospective observational study included all consecutive trauma patients aged 15 years and older admitted into 15 centers contributing to the TraumaBase® registry during the first wave of the SARS-CoV-2 pandemic in France. This COVID-19 trauma cohort was compared to historical cohorts (2017-2019). RESULTS: Over a 4 years-study period, 5762 patients were admitted between the first week of February and mid-June. This cohort was split between patients admitted during the first 2020 pandemic wave in France (pandemic period, 1314 patients) and those admitted during the corresponding period in the three previous years (2017-2019, 4448 patients). Trauma patient demographics changed substantially during the pandemic especially during the lockdown period, with an observed reduction in both the absolute numbers and proportion exposed to road traffic accidents and subsequently admitted to traumacenters (348 annually 2017-2019 [55.4% of trauma admissions] vs 143 [36.8%] in 2020 p < 0.005). The in-hospital observed mortality and predicted mortality during the pandemic period were not different compared to the non-pandemic years. CONCLUSIONS: During this first wave of COVID-19 in France, and more specifically during lockdown there was a significant reduction of patients admitted to designated trauma centers. Despite the reallocation and reorganization of medical resources this reduction prevented the saturation of the trauma rescue chain and has allowed maintaining a high quality of care for trauma patients.

Preventing the Long-term Effects of General Anesthesia on the Developing Brain: How Translational Research can Contribute.

In 2017, the Food and Drug Administration published a safety recommendation to limit the exposure to general anesthesia as much as possible below the age of three. Indeed, several preclinical and clinical studies have questioned the possible toxicity of general anesthesia on the developing brain. Since then, recent clinical studies tried to mitigate this alarming issue. What is true, what is false? Contrary to some perceptions, the debate is not over yet. Only stronger translational research will allow scientists to provide concrete answers to this public health issue. In this review, we will provide and discuss the more recent data in this field, including the point of view of preclinical researchers, neuropsychologists and pediatric anesthesiologists. Through translational research, preclinical researchers have more than ever a role to play to better understand and identify long-term effects of general anesthesia for pediatric surgery on brain development in order to minimize it.

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Cervical arterial abnormalities and outcome after aneurysmal subarachnoid haemorrhage: A pilot cohort study.

BACKGROUND: Cervical arterial abnormalities are associated with intracranial aneurysm but their frequency and association with outcome in case of aneurysmal subarachnoid haemorrhage (aSAH) remains unknown. METHODS: Data were retrospectively extracted from a prospective database. Consecutive angiographies of aSAH patients on a 13-month period were reviewed as well as consecutive angiographies of SAH patients without evidence of aneurysm on a 20-month period. Occurrence of secondary neurological complications was collected with 3-month functional outcome (modified Rankin Scale ≥ 3 was considered as poor outcome). Cervical arterial abnormalities on angiographies were classified into two subcategories: trajectory and lumen vessel abnormalities. RESULTS: Forty-five patients displayed aneurysmal rupture (aSAH) while 39 patients had no evidence of aneurysm (non-aneurysmal SAH). Prevalence of cervical arterial abnormalities in aSAH and non-aneurysmal SAH patients were 82% (n = 37) and 64% (n = 25), respectively (p = 0.082). Lumen vessel abnormalities were significantly more frequent in case of aSAH (n = 31; 69%) than non-aneurysmal SAH: (n = 9; 23%; p < 0.001). Twenty-eight (62%) aSAH patients experienced poor outcome at 3 months. Lumen vessel abnormalities were significantly associated with 3-month poor outcome (74% (n = 23) versus 36% (n = 5); p = 0.021) without any significant increased occurrence of secondary complications such arterial vasospasm or delayed cerebral ischemia. CONCLUSION: Cervical arterial abnormalities are frequent in a cohort of aSAH patients. Lumen vessel abnormalities are associated with 3-month poor outcome.

Effect of Oral Carbohydrate Intake During Labor on the Rate of Instrumental Vaginal Delivery: A Multicenter, Randomized Controlled Trial.

BACKGROUND: Carbohydrate intake during physical exercise improves muscle performance and decreases fatigue. We hypothesized that carbohydrate intake during labor, which is a period of significant physical activity, can decrease the instrumental vaginal delivery rate. METHODS: In a multicenter, prospective, randomized, controlled trial, healthy adult pregnant women presenting with spontaneous labor were assigned to a "Carbohydrate" group (advised to drink 200 mL of apple or grape juice without pulp every 3 hours) or a "Fasting" group (water only). The primary outcome was the instrumental vaginal delivery rate. Secondary outcomes included duration of labor, rate of cesarean delivery, evaluation of maternal hunger, thirst, stress, fatigue, and overall feeling during labor by numeric rating scale (0 worst rating to 10 best rating), rate of vomiting, and hospital length of stay. Statistical analysis was performed on an intention-to-treat basis. The primary outcome was tested with the "Fasting" group as the reference group. The P values for secondary outcomes were adjusted for multiple comparisons. The differences between groups are reported with 99% confidence interval (CI). RESULTS: A total of 3984 women were analyzed (2014 in the Carbohydrate group and 1970 in the Fasting group). There was no difference in the rate of instrumental delivery between the Carbohydrate (21.0%) and the Fasting (22.4%) groups (difference, -1.4%; 99% CI, -4.9 to 2.2). No differences were found between the Carbohydrate and the Fasting groups for the duration of labor (difference, -7 minutes; 99% CI, -25 to 11), the rate of cesarean delivery (difference, -0.3%; 99% CI, -2.4 to 3.0), the rate of vomiting (difference, 2.8%; 99% CI, 0.2-5.7), the degree of self-reported fatigue (difference, 1; 99% CI, 0-2), self-reported hunger (difference, 0; 99% CI, -1 to 1), thirst (difference, 0; 99% CI, -1 to 1), stress (difference, 0; 99% CI, -1 to 1), overall feeling (difference, 0; 99% CI, 0-0), and the length of hospitalization (difference, 0; 99% CI, -1 to 0). CONCLUSIONS: Carbohydrate intake during labor did not modify the rate of instrumental vaginal delivery.

Impact of 12/15-Lipoxygenase on Brain Injury After Subarachnoid Hemorrhage.

Background and Purpose- Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Oxidative stress contributes to brain injury, but the mechanisms have been poorly studied. Here, we evaluated the role of 12/15-lipoxygenase (12/15-LOX), an enzyme known to cause cell death in ischemic stroke, on brain injury in a mouse model of SAH. Methods- C57Bl6 wild-type mice and Alox15 knockout mice were subjected to SAH using a direct blood injection technique. In SAH wild-type mice, half received the 12/15-LOX inhibitor ML351 and half received vehicle. Immunohistochemistry, brain edema, blood-brain barrier leakage and functional outcomes were assessed 1 and 3 days after SAH induction. Results- SAH led to increased 12/15-LOX in macrophages of the brain parenchyma, adjacent to the subarachnoid blood. Neuronal cell death after SAH was reduced by ML351 and in Alox15 knockout mice. Similarly, SAH induced brain edema, which was 12/15-LOX dependent. Finally, Alox15 gene knockout and inhibitor treatment in wild-type mice with SAH led to an improved behavioral outcome. Conclusions- 12/15-LOX is overexpressed in macrophages after SAH in mice, and inhibition of the 12/15-LOX pathway decreases brain injury and improves neurological outcome. This study suggests 12/15-LOX as a novel therapeutic target to limit brain injury after SAH.

The Fragility and Reliability of Conclusions of Anesthesia and Critical Care Randomized Trials With Statistically Significant Findings: A Systematic Review.

OBJECTIVES: The Fragility Index, which represents the number of patients responsible for a statistically significant finding, has been suggested as an aid for interpreting the robustness of results from clinical trials. A small Fragility Index indicates that the statistical significance of a trial depends on only a few events. Our objectives were to calculate the Fragility Index of statistically significant results from randomized controlled trials of anesthesia and critical care interventions and to determine the frequency of distorted presentation of results or "spin". DATA SOURCES: We systematically searched MEDLINE from January 01, 2007, to February 22, 2017, to identify randomized controlled trials exploring the effect of critical care medicine or anesthesia interventions. STUDY SELECTION: Studies were included if they randomized patients 1:1 into two parallel arms and reported at least one statistically significant (p < 0.05) binary outcome (primary or secondary). DATA EXTRACTION: Two reviewers independently assessed eligibility and extracted data. The Fragility Index was determined for the chosen outcome. We assessed the level of spin in negative trials and the presence of recommendations for clinical practice in positive trials. DATA SYNTHESIS: We identified 166 eligible randomized controlled trials with a median sample size of 207 patients (interquartile range, 109-497). The median Fragility Index was 3 (interquartile range, 1-7), which means that adding three events to one of the trials treatment arms eliminated its statistical significance. High spin was identified in 42% (n = 30) of negative randomized controlled trials, whereas 21% (n = 20) of positive randomized controlled trials provided recommendations. Lower levels of spin and recommendations were associated with publication in journals with high impact factors (p < 0.001 for both). CONCLUSIONS: Statistically significant results in anesthesia and critical care randomized controlled trials are often fragile, and study conclusions are frequently affected by spin. Routine calculation of the Fragility Index in medical literature may allow for better understanding of trials and therefore enhance the quality of reporting.