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TREOCAPA: prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen—statistical analysis plan for the randomized phase III group sequential trial
No full textInternational audienceBackgroundPersistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Controversies persist about the management of PDA in extremely preterm infants. PDA is associated with morbidities, but no therapeutic strategy has resulted in an improved neonatal outcome. Acetaminophen appears to be a promising alternative with possibly fewer adverse effects. The primary objective is to determine whether a prophylactic pharmacological intervention with acetaminophen may increase the survival without severe morbidity at postmenstrual age of 36 weeks.Methods and analysisTREOCAPA phase III is a randomized, multicenter, double-blind, stratified, placebo-controlled superiority trial, two arms in a 1:1 ratio performed in 43 NICUs of 14 European countries, evaluating whether the intervention increases the survival without severe morbidity by 10%, from 50% in control arm to 60% in treatment arm, until the age of 36 postmenstrual weeks. To detect this difference, 794 patients were required using a group sequential design. Recruitment has been closed, with 803 patients enrolled. Patients eligible for inclusion are preterm infants with a gestational age between 23 and 28 weeks. In the acetaminophen group, 20 mg/kg loading dose within 12 h after birth, followed by 7.5 mg/kg quarter in die (QID) for 5 days, will be administered to the 27–28 weeks gestational age group, and 25 mg/kg loading dose then 10 mg/kg QID will be administered to the 23–26 weeks gestational age group. The severe morbidities include severe bronchopulmonary dysplasia (BPD grade 3) according to NIH consensus, necrotizing enterocolitis (NEC) of Bell’s stage II or III, intraventricular hemorrhage (IVH) grade III–IV according to Papile classification, or cystic leukomalacia.DiscussionWhatever the results, the conclusions of this study should be informative for the neonatal scientific community. The results will either confirm the benefit of treatment in increasing survival without severe morbidity, or indicate a worsening of outcomes with prophylactic acetaminophen treatment, or show no difference in the primary outcome. In the latter case, ultrasonographic assessments of ductus arteriosus status on day 7 may help explain the absence of a difference. This could indicate that acetaminophen is ineffective in promoting ductal closure or that early closure of the ductus arteriosus is inconsequential if, despite more frequent closures, there is no associated improvement in outcomes
Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium
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Clinical significance criteria in the ICSD and DSM sleep disorder classifications: a content overlap analysis using the Jaccard index
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Association Between Surgeon Stress and Major Surgical Complications
No full textInternational audienceImportance. Surgeon stress can influence technical and nontechnical skills, but the consequences for patient outcomes remain unknown.Objective. To investigate whether surgeon physiological stress, as assessed by sympathovagal balance, is associated with postoperative complications.Design, Setting, and Participants. This multicenter prospective cohort study included 14 surgical departments involving 7 specialties within 4 university hospitals in Lyon, France. Exclusion criteria consisted of patient age younger than 18 years, palliative surgery, incomplete operative time-stamping data, procedures with a duration of less than 20 minutes, and invalid surgeon heart rate variability (HRV) data. Data were accrued between November 1, 2020, and December 31, 2021, with 30-day follow-up completed on May 8, 2022. Analyses were performed from January 1 to May 31, 2024.Exposure. Sympathovagal balance of the attending surgeon in the first 5 minutes of surgery.Main Outcomes and Measures. Major surgical complications, extended intensive care unit stay, and mortality within 30 days, after adjustment via mixed-effects multivariable logistic regression for surgeon age, professional status, the time of incision, the random effect of the surgeon, and a composite risk score incorporating patient comorbidities and surgery characteristics. Sympathovagal balance was quantified by the low frequency to high frequency (LF:HF) ratio derived from HRV data measured by chest monitors worn intraoperatively. The LF:HF ratio was normalized at the surgeon level to the median value observed for each surgeon during the study period to control for baseline differences.Results. A total of 793 surgical procedures performed by 38 attending surgeons were included in the analysis. Median patient age was 62 (IQR, 47-72) years, and 412 (52.0%) were female, with a median of 2 (IQR, 1-4) comorbidities. Median surgeon age was 46 (IQR, 39-52) years, 39 (78.9%) were male, and 22 (57.9%) were professors. Median surgeon heart rate was 88 (IQR, 77-99) beats per minute. Median surgeon LF:HF ratio was 7.16 (IQR, 4.52-10.72) before and 1.00 (IQR, 0.71-1.32) after normalization. Increased surgeon sympathovagal balance during the first 5 minutes of surgery was associated with significantly reduced major surgical complications (adjusted odds ratio [AOR], 0.63; 95% CI, 0.41-0.98; P = .04), though not with reduced intensive care unit stay (AOR, 0.34; 95% CI, 0.11-1.01; P = .05) or mortality (AOR, 0.18; 95% CI, 0.03-1.03; P = .05).Conclusions and Relevance. Increased surgeon stress at the beginning of a procedure was associated with improved clinical patient outcomes. The results are illustrative of the complex relationship between physiological stress and performance, identify a novel association between measurable surgeon human factors and patient outcomes, and may highlight opportunities to improve patient care
Development of a 50% (w/v) aluminium chloride hexahydrate solution as haemostatic agent
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Muscle composition is not a prognostic factor for muscle strength recovery after anterior cruciate ligament surgery by hamstring tendon autograft
No full textInternational audiencePurpose: For the athlete, anterior Cruciate Ligament (ACL) rupture and its surgical management are often aturning point in their career. Success and time to return to sport are essential parameters for athletes and theirsupport staff, so it is critical to understand the prognostic factors influencing return to sport after anteriorcruciate ligament reconstruction (ACLR). The aim of this study was to determine the influence of hamstringmuscle composition on muscle power following ACLR with autogenous hamstring grafts.Methods: 24 patients with chronic torn ACL were included at a single-center over a period of 17 months. Theyunderwent surgical repair and during this procedure grafts were harvested from the gracilis and the semitendinosus.Muscle composition was assessed on the remaining proximal part of the semitendinosus muscle, which isusually discarded, by immunostaining. Muscle power was defined by comparing the strength of the operated legand the healthy leg on an isokinetic dynamometer at 6 months according a standardized protocol after 6 monthsof outpatient rehabilitation. Various other intrinsic and extrinsic factors were also studied, such as body massindex (BMI), age, sex, smoking, or sport practiced, to determine factors influencing isokinetic strength test afterACLR.Results: No statistical relationship was identified between muscle composition and the muscle power between theoperated and healthy leg. Smoking and female gender were associated with worse muscle recovery. Age and BMIhad no influence on isokinetic performance at 6 months.Conclusion: Following ACLR muscle composition is not associated with difference in strength between the twolegs at 6 months. Determining muscle fiber composition of the patient does not inform the rehabilitation protocolor predict muscle strength recovery. Larger series data is required to understand the influence of gender or tobaccoon muscle fiber characteristic.Level of Evidence: : I; Prospective prognostic study
Spacers in two-stage strategy for periprosthetic infection
No full textInternational audienceIn two-stage revision of infected implants, the first stage involves removing the implant and implanting a joint spacer, and the second stage involves implanting a new prosthesis at least 6 weeks later. Spacers have two main functions: local administration of high-dose antibiotics, and preservation of the joint space by reducing soft tissue retraction and improving patient comfort until reimplantation. The present review aims to detail the necessary characteristics of antibiotics added to cement to achieve good joint diffusion, to describe the steps of two-stage revision, and to present the types of spacer available according to the joint and complications. The antibiotic used in the spacer must be heat-resistant, water-soluble and chemically stable in the cement. Gentamicin and vancomycin are generally preferred. We recommend at least 3 months’ systematic antibiotic therapy for periprosthetic joint infection. Reimplantation is performed either at 6 weeks without antibiotic washout or 3 months after 2 weeks’ washout Spacers may be static (non-articulating) or dynamic (articulating). Static spacers are mainly used in the knee or hip in cases of severe bone defect or risk of soft-tissue lesions. An articulating spacer enables some joint functions to be preserved in the knee, hip or shoulder. The most frequent complications are the dislocation of dynamic spacers and the breakage of static or dynamic spacers. To optimize efficacy and minimize complications, the biomechanical and bacteriological characteristics of spacers must be considered.Level of evidenceExpert opinion
Multi-modal refinement of the human heart atlas during the first gestational trimester
No full textUnderstanding human cardiac development is essential to improving the diagnosis and treatment of congenital heart defects. Here, we present a multi-modal atlas of the developing human fetal heart during the critical first trimester. Using single-nucleus RNA sequencing, we sampled nearly 50,000 cardiac nuclei from three human fetuses at 8.6, 9.0, and 10.7 post-conceptional weeks (pcw). This dataset enabled distinction of 21 cell types, including novel contractile, conductive, and stromal cells. Lymphatic endothelial, epicardial and autonomic neural and glial cells were among the new, smaller populations for which we established high-resolution transcriptional profiles. We further integrated the snRNAseq data with published single-cell RNAseq data from hearts between 5 to 7 pcw. Combined trajectory analysis allowed us to identify a new human cardiomyofibroblast progenitor, preceding the segregation and diversification of cardiomyocyte and many stromal lineages. To refine cell-type annotations, we turned to spatial transcriptomics. Analysis of six Visium sections from two additional hearts was aided by deconvolution of spots with our snRNAseq data. We further confirmed key markers using in situ hybridization or immunofluorescence on sectioned or whole hearts, followed by standard or light-sheet confocal microscopy. Altogether, these complementary approaches permitted us to add anatomical-positional features such as chamber specificities, innervation and conduction system components, or subdomains of the atrioventricular septation complex. Each translates cell identity into specialized cardiac functions. A total of forty first-trimester hearts were studied to discover and validate cellular characteristics across a wide range of scales, from the individual nucleus to the entire organ. Our results offer a comprehensive resource for understanding the cellular dynamics of human cardiac development and lay the groundwork for further studies into the molecular mechanisms underlying congenital heart malformations. This atlas adds unprecedented spatial and temporal resolution to the characterization of human-specific aspects of early human heart formation
Partially hydrolyzed, whey-based infant formula with six human milk oligosaccharides, B. infantis LMG11588, and B. lactis CNCM I-3446 is safe, well tolerated, and improves gut health: a staged analysis of a randomized trial
No full textInternational audienceBackground and aims Gut health and microbiome development are closely linked in early life, with human milk oligosaccharides (HMOs) playing a key role. This study reports results through 4 months of age from a trial evaluating an infant formula containing a synbiotic blend of HMOs and probiotics, focusing on growth, gastrointestinal (GI) tolerance, and gut health biomarkers from birth to 15 months. Materials and methods Healthy infants aged ≤14 days were randomized to receive either the experimental formula (SYN; control formula supplemented with six HMOs and two probiotics [ B. infantis , B. lactis ]) or the control formula (CTRL; partially hydrolyzed 100% whey-based formula). A non-randomized breastfed (BF) group served as a reference. The primary endpoint was weight gain velocity in SYN vs. CTRL through 4 months of age. Secondary endpoints included fecal outcomes (abundance of bifidobacteria, immune and gut health markers), GI tolerance, and adverse events (AEs). Results The full analysis set (FAS) included 313 infants (118 in SYN, 114 in CTRL, and 81 BF), while the per-protocol population (PP) included 227 infants (84 in SYN, 84 in CTRL, and 59 BF). Weight gain velocity through 4 months in the SYN group was non-inferior to that in the CTRL group in both FAS and PP analyses (both p < 0.0001). Parent-reported GI tolerance and stool patterns were similar between SYN and CTRL groups through 4 months. At 3 months, Bifidobacteria abundance was significantly higher in the SYN group compared to the CTRL group ( p = 0.004). Fecal pH was lower in the SYN group than in the CTRL group ( p = 0.018) and more closely resembled that of the BF group. Immune and gut health markers were similar between the SYN and BF groups. No significant differences in AEs were observed across groups. Conclusion The synbiotic-supplemented infant formula supported healthy, age-appropriate growth, good GI tolerance, and increased the abundance of beneficial bifidobacteria through 4 months of age. Clinical trial registration https://clinicaltrials.gov/study/NCT04962594
Humoral immune response to Covid-19 vaccination in patients with cancer – Results from the ANRS0001S COV-POPART study
No full textInternational audienceBackground: Patients with cancer, whose immune responses to vaccines are commonly weaker than those of the general population, are recommended a booster dose after two initial doses of Covid-19 vaccine. Our objective was to compare the humoral immunogenicity of Covid-19 vaccines in patients with cancer compared to healthy adults (control group) after primary vaccine series and after a booster dose.Methods: We included participants aged ≤75 and vaccinated with two doses in the primary vaccine series and a booster, from the French national prospective Covid-19 vaccine cohort study (ANRS0001S COV-POPART) and excluded those with SARS-CoV-2 infection. Percentage of responders, geometric mean titers (GMT) of anti-SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies against original strain, Delta and Omicron variants of concern, were estimated one month after the primary vaccine series, then one month and six months after a booster dose.Results: We included 183 patients with cancer and 1173 controls. The most frequent cancers were breast (37.2 %) and lung cancer (17.5 %). Patients with cancer were older and had lower anti-Spike IgG levels after the primary vaccine series (GMT = 132.4 vs 332.7 BAU/mL, P < 0.0001), but they developed similar response at one month (GMT = 2146.1 vs 1841.3 BAU/mL], P = 0.16) and six months after booster (602.0 vs 574.4 BAU/mL, P = 0.80). Neutralizing antibodies levels confirmed these results.Conclusion: Patients with cancer have comparable response rates to controls one month and six months after a booster dose. Our results support the benefit of a booster dose in patients with cancer