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Reduced monocyte HLA-DR expression, a hallmark of immunosuppression in sepsis, is associated with infectious complications and mortality. Therapeutic strategies, including IFN-γ, have been used to restore monocyte HLA-DR and immune function, but have not consistently improved clinical outcomes. Therefore, we conducted an iterative series of experiments to re-examine the core assumptions and address the key gaps in the current understanding. We conducted a prospective cohort study of patients admitted to the intensive care unit (ICU) with sepsis (n = 55, 36% mortality) to characterize the dynamics of monocyte HLA-DR expression and associated functional pathways. Flow cytometry was used to evaluate monocyte phenotype, and lipopolysaccharide (LPS) stimulation was used to assess monocyte functional capacity. We examined canonical monocyte pathways and identified those that were responsive to LPS stimulation and/or modulated by IFN-γ . We evaluated monocyte HLA-DR expression in the peripheral blood and inflamed tissues of healthy volunteers following intradermal administration of UV-killed . Monocyte HLA-DR expression was significantly lower in patients than in healthy volunteers, particularly in non-survivors. Monocyte phenotypes evolved discordantly over time, some markers trended toward healthy levels, while others diverged, with no consistent distinction between survivors and non-survivors. Intracellular trafficking of membrane HLA-DR on bacterial phagocytosis contributes to the reduced surface HLA-DR expression. Compared to healthy volunteers, monocytes from ICU patients had a significantly lower expression of proteins associated with antigen presentation and co-stimulation, cytokines, phagocytosis, and a blunted response to LPS. IFN-γ increased the levels of proteins involved in antigen presentation, but their expression remained significantly lower than that in healthy controls. Healthy volunteers demonstrated compartment-specific and temporally distinct regulation of monocyte HLA-DR in circulation versus that in inflamed tissue. Reduced monocyte HLA-DR expression in sepsis reflects broad disruptions across multiple pathways, explaining the limited efficacy of therapeutic interventions. Further insights into the mechanisms governing therapeutic modulation of monocyte HLA-DR and immune function are required to identify patients who are most likely to benefit from intervention.

Background Out-of-plane (OOP) approach is frequently used for ultrasound-guided insertion of central venous catheter (CVC) owing to its simplicity but does not avoid mechanical complication. In-plane (IP) approach might improve safety of insertion; however, it is less easy to master. We assessed, a homemade needle guide device aimed to improve CVC insertion using IP approach. Method We evaluated in a randomized simulation trial, the impact of a homemade needle guide on internal jugular, subclavian and femoral vein puncture, using three approaches: out-of-plane free hand (OOP-FH), in-plane free hand (IP-FH), and in-plane needle guided (IP-NG). Success at first pass, the number of needle redirections and arterial punctures was recorded. Time elapsed (i) from skin contact to first skin puncture, (ii) from skin puncture to successful venous puncture and (iii) from skin contact to venous return were measured. Results Thirty operators performed 270 punctures. IP-NG approach resulted in high success rate at first pass (jugular: 80%, subclavian: 95% and femoral: 100%) which was higher than success rate observed with OOP-FH and IP-FH regardless of the site ( p  = .01). Compared to IP-FH and OOP-FH, the IP-NG approach decreased the number of needle redirections at each site ( p  = .009) and arterial punctures ( p  = .001). Compared to IP-FH, the IP-NG approach decreased the total procedure duration for puncture at each site. Conclusion In this simulation study, IP approach using a homemade needle guide for ultrasound-guided central vein puncture improved success rate at first pass, reduced the number of punctures/redirections and shortened the procedure duration compared to OOP and IP free-hand approaches.

•First method allowing simultaneously measurement of 4-MEC and MDPV in hair.•Very sensitive method with LLOQ set at 1pg/mg for both compounds.•First 4-MEC result in hair in a chronic abuser of this compound. 4-Methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV) are synthetic cathinones. The objective of this study was to develop a method in order to measure these compounds in hair of a patient. After decontamination, 20mg of hair were grinded and incubated in phosphate buffer pH 5.0 in presence of 100ng of MDMA-d5 used as internal standard. Double basic liquid–liquid extraction was performed. Samples were separated on a 1.9μm Hypersil GOLD PFP column (100×2.1mm) using gradient elution. Compounds were detected by a LCQ TSQ Vantage XP triple-quadrupole mass spectrometer. SRM transitions m/z 192.1→146.1 and 174.2, m/z 276.1→175.0 and 205.1 and m/z 199.1→165.1 were used for 4-MEC, MDPV and IS, respectively. The assay was accurate and precise over the range 0.001 (lower limit of quantification) to 1ng/mg in hair. No matrix effect was observed. The method has been applied to a 30-year-old man who usually consumed cathinones for 6 months administered intravenously and was admitted to a general hospital for delirious and tachycardia after absorption of 10g of a powder sold as 4-MEC and 5g of MDPV. Both 4-MEC (30ng/mg) and MDPV (1ng/mg) were identified in the hair at high concentrations showing a regular consumption of these drugs. Many others compounds were also identified (mephedrone, MDMA, MDA, cocaine and metabolites, tramadol, hydroxyzine, aripiprazole, haloperidol). Few data are available on concentration of these new designer drugs in hair however important in order to determine the acute or chronic consumption of these drugs.

IntroductionAntineoplastic drugs (AD) are potentially carcinogenic and/or reprotoxic molecules. Healthcare professionals are increasingly exposed to these drugs and can be potentially contaminated by them. Internal contamination of professionals is a key concern for occupational physicians in the assessment and management of occupational risks in healthcare settings. Objectives of this study are to report AD internal contamination rate in nursing staff and to identify factors associated with internal contamination.Methods and analysisThis trial will be conducted in two French hospital centres: University Hospital of Bordeaux and IUCT-Oncopole of Toulouse. The target population is nurses practicing in one of the fifteen selected care departments where at least one of the five studied AD is handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The trial will be conducted with the following steps: (1) development of analytical methods to quantify AD urine biomarkers, (2) study of the workplace and organization around AD in each care department (transport and handling, professional practices, personal and collective protection equipments available) (3) development of a self-questionnaire detailing professional activities during the day of inclusion, (4) nurses inclusion (urine samples and self-questionnaire collection), (5) urine assays, (6) data analysis.Ethics and disseminationThe study protocol has been approved by the French Advisory Committee on the Treatment of Information in Health Research (CCTIRS) and by the French Data Protection Authority (CNIL). Following the opinion of the Regional Committee for the Protection of Persons, this study is outside the scope of the provisions governing biomedical research and routine care (n°2014/87). The results will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration number NCT03137641.

PurposeOur objective was to assess burnout prevalence rates among physicians practicing in Europe (regardless of their specialty) taking into account the main approaches used to define burnout with the Maslach Burnout Inventory (MBI) tool.MethodsA systematic review was carried out from 2006 to 2018. A keyword request was obtained using the PubMed/Medline, Web of Science and Banque de Données en Santé Publique search engine. Studies written in English measuring burnout with the MBI tool among a population of practicing European physicians were selected. Data were extracted and classified according to burnout’s definition provided by the authors. Three definitions using the MBI dimensions were considered: tri-, bi- and unidimensional definition. A meta-analysis was then performed on burnout prevalence rates according to the dimensional definition of burnout.ResultsFrom 2378 search results, we selected 56 studies including from up to 41 European countries. Depending upon the study, physicians’ burnout prevalence rates ranged from 2.5% to 72.0%. The pooled prevalence rate of burnout was estimated at 7.7% [5.3–10.4%] with the tridimensional definition, 19.7% [13.5–26.3%] with the bidimensional definition and 43.2% [29.0–57.6%] with the unidimensional definition.ConclusionBurnout pooled prevalence among physicians varies from single to fivefold depending on the method employed to assess burnout with the MBI tool. Medical community should determine a standardized method to assess burnout prevalence rates to best evaluate this phenomenon.

Based on animal studies, 2-propanol seems to have twice the central nervous system depressing effects of ethanol at similar concentrations, due to its higher molecular weight (60.02 g/mol) in comparison to ethanol (46.07 g/mol) as well as the additive effect of its metabolite, acetone [6]. Ethanol is first quickly oxidized to acetaldehyde by ADH and further metabolized to acetic acid by aldehyde dehydrogenase, both resulting in the generation of reduced nicotinamide adenine dinucleotide (NADH). See PDF.] Biochemical pathways of ethanol-related increase in plasma lactate concentration (adapted from [10]) Finally, although the contribution of 2-propanol to toxicity was not fully considered in their report [1], no specific treatment other than the supportive management provided would have been useful because acetone itself is neither life-threatening nor causes significant end-organ damage [5, 7], treatment with fomepizole is unnecessary.

Background Listeriosis is a rare but severe foodborne infection, particularly affecting immunocompromised individuals and older adults. Severe cases may lead to neurolisteriosis and sepsis, necessitating intensive care unit (ICU) admission. This study aims to analyze the demographic characteristics, clinical presentation, microbiological findings, treatments, and outcomes of critically ill patients with Listeria infections in the ICU. Methods A retrospective multicenter study was conducted across 23 French hospitals over a 10-year period, including ICU patients with culture-confirmed Listeria monocytogenes infections. Data on demographics, comorbidities, ICU admission characteristics, biological and microbiological parameters, treatments, and outcomes were collected. The primary outcome was ICU mortality. A multivariable logistic regression model was used to identify factors associated with mortality in patients with neurological manifestations. Results A total of 110 patients were included, with a median age of 68 years; 61% were male, and 71% were immunocompromised. Neurological involvement was present in most cases. Invasive mechanical ventilation was required in 58% of patients, and vasopressor support in 44%. ICU and in-hospital mortality rates were 25% and 32%, respectively. Among patients with neurolisteriosis, each 1-point decrease in Glasgow Coma Scale score at admission was associated with increased mortality (OR, 1.22; 95% CI 1.05–1.45; p = 0.009), as were higher cerebrospinal fluid (CSF) protein levels (OR, 1.56; 95% CI 1.15–2.41; p = 0.028). Steroid use was not significantly associated with reduced mortality (OR, 0.30; 95% CI 0.07–1.05; p = 0.076). Conclusion Listeriosis requiring ICU admission is associated with high morbidity and mortality, particularly in older and immunocompromised patients. The severity of these infections is reflected by the frequent need for organ support. Further research is needed to clarify the potential role of steroids in neurolisteriosis.

ObjectiveEstimate the effort–reward imbalance prevalence (ERI) among physicians.MethodsA systematic review was conducted from 2005 to 2019 using PRISMA guidelines on the PubMed and EBSCOhost search engines. Data were classified according to the ERI definition used by the authors. A meta-analysis was performed on effort and reward scores and on ERI prevalence rates.ResultsOut of 3787 results, we selected 41 studies. The physicians’ ERI prevalence rate ranged from 3.50 to 96.9%. The standardized pooled effort mean score was 58.5 for effort and 48.9 for a reward out of 100, respectively. The overall combined ERI rate (when the ratio between effort and reward scores was above 1) was 40.2% among 21,939 practitioners (31.7% in the working European population). ERI rate was 70.2% using a four-point Likert scale and 21.1% using a five-point Likert scale. The highest rate (96.9%) was observed among German rural general practitioners and the lowest rate (3.50%) among Swiss hospital practitioners. The low percentage of variability (I2 = 27%) attributed to effort scores heterogeneity between studies suggested that this dimension is not discriminant in the physician ERI assessment. The high heterogeneity in reward scores (I2 = 83%) indicated that this dimension is sensible in ERI assessment among physicians. The number of items used did not appear as a significant source of heterogeneity.ConclusionPhysician job ERI appeared to be higher than in the working population. Studying each dimension and item indicators could help improve psychosocial risk prevention.

Purpose Humoral immunity proteins—immunoglobulins, complement proteins, and antimicrobial peptides—have key antimicrobial and immunomodulatory functions in sepsis. We hypothesised that their circulating levels are lower in non-survivors, potentially resulting in impaired bacterial clearance and persistent or recurrent infections. Methods We performed a systematic review and meta-analysis evaluating differences in humoral immunity proteins between survivors and non-survivors in adult patients with sepsis. PubMed and Embase were searched without date restrictions. Random-effects meta-analyses were used to estimate pooled standardised mean differences (SMD) with 95% confidence intervals (CI). Sensitivity analyses included data from the MIMIC-IV ICU database, and further supplemented by three proteomic studies. Results Thirty-six studies including 6,330 patients were analysed. Thirteen reported on immunoglobulins, 17 on complement proteins, and 7 on the antimicrobial peptide heparin-binding protein (HBP). Survivors had significantly higher levels of complement proteins C3 (SMD 0.53 [0.07–0.99]) and C4 (SMD 0.51 [0.09–0.94]) compared to non-survivors. Conversely, C4a (SMD − 1.17 [–1.77 to − 0.56]) and IgA (SMD − 0.21 [–0.39 to − 0.03]) were significantly lower in survivors. No differences were found for IgG (SMD 0.00 [–0.18 to 0.18]), IgM (SMD − 0.02 [–0.13 to 0.08]), C5, C5a, or HBP. Sensitivity analyses using MIMIC-IV ( n  = 2,452) and proteomic datasets supported these findings. Proteomic data revealed early depletion of classical complement components (C3, C4B) and regulatory proteins in non-survivors. Conclusion Sepsis non-survivors exhibit lower C3 and C4 levels and higher C4a, consistent with complement activation and/or depletion. Complement proteins may serve as potential biomarkers and therapeutic targets in sepsis.

ObjectiveThe aim of this study was to assess internal antineoplastic drugs (ADs) contamination in the nursing staff in French hospital centers, using highly sensitive analytical methods.MethodsThis cross-sectional study included nurses practicing in care departments where at least one of the five ADs studied was handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The nurses study participation lasted 24 h including collection of three urine samples and one self-questionnaire. All urine samples were assayed by ultra-high-performance liquid chromatography–tandem mass spectrometry methods with very low value of the lower limit of quantification (LLOQ).Results74 nurses were included, 222 urine samples and 74 self-questionnaires were collected; 1092 urine assays were performed. The percentage of nurses with internal AD contamination was 60.8% and low levels of urinary concentrations were measured. Regarding nurses with internal contamination (n = 45), 42.2% presented internal contamination by methotrexate, 37.8% by cyclophosphamide, 33.3% by ifosfamide, 17.8% by 5-fluorouracil metabolite and 6.7% by doxorubicine. Among the positive assays, 17.9% (n = 26/145) were not explained by exposure data from the self-questionnaire but this could be due to the skin contact of nurses with contaminated work surfaces.ConclusionsThis study reported high percentage of nurses with internal ADs contamination. The low LLOQ values of the used analytical methods, allowed the detection of ADs that would not have been detected with the current published methods: the percentage of contamination would have been 17.6% instead of the 60.8% reported here. Pending toxicological reference values, urine ADs concentrations should be reduced as low as reasonably achievable (ALARA principle).