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Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database
No full textInternational audienceBackground Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM. Methods We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, "Direct ICU" corresponding to a direct ICU admission and "Delayed ICU" corresponding to a secondary ICU admission. Results We identified 4052 patients hospitalized for a first episode of PM, including 2006 "Direct ICU" patients (50%) and 2046 "delayed ICU" patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50-71] and a median Charlson index of 1 [0-3]. Among them, median SAPS II on admission was 46 [33-62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2-14] and 21 days [13-38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56-0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU. Conclusions Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission
Post-exercise energy replacement might lead to reduced subsequent energy intake in women with constitutional thinness: Exploratory results from the NUTRILEAN project
No full textInternational audienceWhile people with Constitutional Thinness (CT) declare a deep willingness to gain weight, there appetitive responses to energy balance manipulations remain unclear. The present work compares the effect of an acute exercise combined or not with an energy replacement load, on subsequent energy intake, appetite and food reward, between normal weight and women with CT. Anthropometric measurements, body composition (Dual X-ray absorptiometry-DXA) and aerobic capacity (VO2max) were assessed in 10 normal-weight (Body Mass Index-BMI): 20-25 kg/m2) and 10 C T (BMI<17.5 kg/m2) women (18-30 years). They randomly performed i) a resting session (CON); ii) an exercise session (EX); iii) an exercise session with energy replacement (EX + R). Their subsequent ad libitum intake, appetite feelings and food reward were evaluated (Leeds-Food-Preference-Questionnaire). CT showed a lower weight (p < 0,001), BMI(p < 0,001), Fat-Mass (%) (p = 0,003) and Fat-Free Mass (kg) (p < 0,001). CT showed a lower ad libitum energy intake on EX + R compared with CON (p = 0,008) and a higher Relative Energy Intake (REI) on CON compared with EX (p = 0,007) and EX + R (p < 0,001). A lower was observed during EX and EX + R compared with CON (p = 0,006,p = 0,009 respectively) in CT. No condition nor group effect was found for hunger. NW only showed a higher pre-meal fullness on EX + R compared to CON and EX (p < 0,001). Choice (p = 0,030), Explicit Liking (p = 0,016), Explicit Wanting (p = 0,004) and Implicit Wanting (p = 0,035) for taste were higher on EX + R than CON and EX. The decreased EI observed in CT when the exercise-induced energy expenditure is compensated by the ingestion of an equivalent energy load, might contribute to explain the difficulty to increase their energy balance and then induce weight gain. Further studies are needed to better understand their energy balance regulation to propose adapted weight gain strategies
Surveillance of multiple congenital anomalies; searching for new associations
No full textInternational audienceMany human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008-2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini-Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered "potential new associations" by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation
Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson’s disease
No full textInternational audiencePostoperative apathy is a frequent symptom in Parkinson’s disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering and ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and one-year postoperative apathy in Parkinson’s disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with one-year postoperative apathy considering: i) preoperative clinical phenotype, ii) dopaminergic drug management and iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and one year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive, and behavioral signs. We modelled the volume of tissue activated in 161 patients using Lead DBS toolbox and analyzed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited one-year postoperative apathy: 67 (18.2%) with “de novo apathy” and 27 (7.4%) with “sustained apathy”. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having “reversed apathy”. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having “no apathy”. We identified preoperative apathy score (OR 1.16, IC95% [1.10 ; 1.22], p<0.001), preoperative episodic memory free recall score (OR 0.93, IC95% [0.88 ; 0.97], p=0.003), and one-year postoperative motor responsiveness (OR 0.98, IC95% [0.96 ; 0.99], p=0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with “sustained apathy” had poorer preoperative fronto-striatal cognitive status and higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (p=0.023), suggesting cognitive dopa-resistant apathy. Patients with “reversed apathy” benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left STN (p=0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage post-operative apathy
Eccentric Muscle Strengthening Using Maximal Contractions Is Deleterious in Knee Osteoarthritis: A Randomized Clinical Trial
No full textInternational audienceObjectives: To show the superiority of eccentric versus concentric strengthening in terms of improving quadriceps strength in knee osteoarthritis (OA), a randomized controlled study was conducted to perform 12 sessions of either eccentric or concentric isokinetic muscle strengthening over 6 weeks. Methods: We recruited males and females, aged between 40 and 70 years, with predominantly unilateral femorotibial OA. Exclusion criteria were having a prosthesis, inflammatory arthritis or flare-up of OA, symptomatic patellofemoral OA, cardiovascular or pulmonary disease that could be a contraindication to the study treatment, and any pathology that could cause muscle weakness. The primary endpoint was the between-group difference in change in maximum concentric isokinetic knee extension peak torque (PT) at 60°/s on the OA side at 6 weeks. Secondary endpoints were between-group difference in change in concentric hamstring PT at 60°/s; eccentric quadriceps and hamstring PT at 30°/s; 10 m and 200 m walking speeds; pain and functional status (WOMAC score) at 6 weeks and 6 months. Results: The sample consisted of 11 females and 27 males, with a mean age of 57.7 ± 7.52 years and a body mass index (BMI) of 25.95 ± 3.93 kg/m2. Quadriceps strength increased more at 6 weeks in the concentric than the eccentric group with no statistical difference. There was a rate of 25% major adverse events in the eccentric group. Conclusions: Eccentric training resulted in a smaller improvement in quadriceps strength than concentric training and was associated with a high risk of muscle injury, particularly to the hamstring muscles
Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting
No full textInternational audienceSarcopenic obesity (SO) is defined as the combination of excess fat mass (obesity) and low skeletal muscle mass and function (sarcopenia). The identification and classification of factors related to SO would favor better prevention and diagnosis. The present article aimed to (i) define a list of factors related with SO based on literature analysis, (ii) identify clinical conditions linked with SO development from literature search and (iii) evaluate their relevance and the potential research gaps by consulting an expert panel. From 4746 articles screened, 240 articles were selected for extraction of the factors associated with SO. Factors were classified according to their frequency in the literature. Clinical conditions were also recorded. Then, they were evaluated by a panel of expert for evaluation of their relevance in SO development. Experts also suggested additional factors. Thirty-nine unique factors were extracted from the papers and additional eleven factors suggested by a panel of experts in the SO field. The frequency in the literature showed insulin resistance, dyslipidemia, lack of exercise training, inflammation and hypertension as the most frequent factors associated with SO whereas experts ranked low spontaneous physical activity, protein and energy intakes, low exercise training and aging as the most important. Although literature and expert panel presented some differences, this first list of associated factors could help to identify patients at risk of SO. Further work is needed to confirm the contribution of factors associated with SO among the population overtime or in randomized controlled trials to demonstrate causality.
CHKA, a potential target marker for early-stage metabolic dysfunction associated steatotic liver disease induced hepatocellular carcinoma with low fibrosis level: analysis by metabolomic and transcriptomic
No full textInternational audienceBackground and Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) can eventually progress to hepatocellular carcinoma (HCC). Thirty to 40% of MASLD-HCC occur in the absence of fibrosis, posing a challenge for early detection. Previously, we reported 2 phenotypes of MASLD-HCC based on the severity of fibrosis (F0F1 vs. F3F4) (Buchard et al., 2021). The objective of this study is to explore lipid metabolism pathways through "omics" and identify biomarkers of MASLD-HCC based on the severity of fibrosis.Method: Our cohort included 56 pairs of tumor and non-tumor (NTT) human liver tissues (F0F1 = 28, F3F4 = 28), and 5 healthy liver tissues (HLT) used as control (CRB Foie). A non-targeted metabolomic analysis by liquid chromatography-mass spectrometry (LC-MS) was performed. In addition, a qRT-PCR analysis focused on a panel of 16 genes involved in the main lipid metabolism pathways was conducted (SPTLC1, SPTLC2, SGMS1, SGMS2, SMPD1, SMPD3, CHKA, PCYT1A, CHPT1, PEMT, MBOAT7, DGAT1, DGAT2, ACAT2, AADACL1 and ACOX1). For each group, TT was compared to NTT and to HLT. The study was approved by the Ethic Committee Sud-Est VI Clermont-Ferrand (Agreement number AU887, 04/03/2011). Results: First, using LC-MS, we identified 130 metabolites and 30 of them exhibited significant difference between TT and NTT. In the MASLD-HCC-F0F1, the levels of ceramide Cer(d18:1/22:0), sphingomyelin SM(41:1) and phosphatidylethanolamine PE(O-16:1_20:4) were decreased. While the levels of SM(35:1), SM(40:2), SM(42:3), phosphatidylcholines PC(16:0_14:0), PC(16:0/16:0), PC(18:0_18:1), PC(40:8) and PE(18:0_18:1) were increased. In contrast, most of metabolites content in MASLD-HCC-F3F4 were reduced compared to NTT, indicating an amplified anabolism. However, the levels of PC(18:0_18:1), PC(18:0_20:3) and phosphatidylinositol PI(16:0_18:1) were increased. Notably, PI(16:0_18:1) is considered as an onco-metabolite (Yang et al., 2018). Second, transcriptomic data revealed that in MASLD-HCC-F0F1, among the 16 genes studied, the expression of 6 genes coding for CHKA, DGAT1, MBOAT7, SPTLC2, SMPD1 and SGMS1 was up-regulated. However, MASLD-HCC-F3F4 shown no variation in the expression of these genes. Altogether, this data supports the existence of 2 MASLD-HCC phenotypes according to fibrosis severity. Furthermore, the increased expression of CHKA in MASLD-HCC-F0F1 is in line with our previous metabolomic data, reporting a significant accumulation of phosphocholine derivatives in MASLD-HCC-F0F1. This observation suggests that choline may serve as an imaging marker to detect HCC-F0F1.Conclusion: "Omics" analyses allow: 1) discrimination of MASLD-HCC based on fibrosis severity; 2) propose CHKA as a marker for MASLD-HCC-F0F1, which could lead to a clinical application: labeled choline may be favored as a more effective tracer for PET scanning in HCC patients with minimal fibrosis
Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey
No full textInternational audienceIntroduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. Methods and analysis The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. Trial registration NCT05228041 /DRI_2021/0030
Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial
No full textInternational audienceBackground: 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.)