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Thyroidectomy without radioiodine in patients with low-risk thyroid cancer: 5 years of follow-up of the prospective randomised ESTIMABL2 trial
No full textInternational audienceBackground ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (¹³¹I) administration compared with a postoperative ¹³¹I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up.Methods Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1•1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone). Follow-up consisted of annual thyroglobulin and thyroglobulin antibody determinations during levothyroxine treatment and neck ultrasonography in odd-numbered years. An event was defined as abnormal foci of ¹³¹I uptake on the post-treatment whole-body-scan requiring subsequent treatment, abnormal neck ultrasonography, elevated thyroglobulin levels, increasing titres or appearance of thyroglobulin antibody (using the same laboratory assay), or a combination of these definitions. Non-inferiority of the proportion of patients without an event in one group compared with the other at 5 years after randomisation was shown if this proportion and its CI did not differ by more than -5%. This study was registered on ClinicalTrials.gov (NCT01837745) and is completed. FindingsOf the 776 patients (n=642 [82•7%] female and n=134 [17•3%] male, median age 52•9 years [IQR 42•6-63•1]) enrolled, 698 were evaluable at 5 years. The proportions of patients without events were 93•2% in the no-radioiodine group and 94•8% in the radioiodine group, for a difference of -1•6% (90% CI -4•5 to 1•4). Events consisted of structural or functional abnormalities (n=11) and biological abnormalities (n=31).Interpretation The non-inferiority of a follow-up strategy compared with postoperative ¹³¹I administration in low risk differentiated thyroid cancer was confirmed at 5 years. There is no loss of opportunity in following these patients without postoperative ablation.Funding Programme de Recherche Hospitalier Clinique.</div
Oncological Safety and Diagnostic Yield of Percutaneous Needle-core Biopsies in Upper Tract Urothelial Carcinoma: The UPERCUT Study
No full textInternational audienc
A genome-wide investigation of Mycoplasma hominis genes associated with gynecological infections or infertility
No full textInternational audienceBackground and aim Mycoplasma hominis is a human pathogenic bacterium that causes a wide range of genital infections and reproductive issues. Previously, based on an extended multilocus sequence typing scheme, we provided evidence for the segregation of M. hominis clinical strains into two distinct pathotypes: gynecological infections or infertility. Here, based on whole genome sequencing (WGS) data, we sought to provide a more refined picture of the phylogenetic relationship between these two M. hominis pathotypes, with the aim to delineate the underlying genetic determinants. Methods We carried out WGS of 62 Tunisian M. hominis clinical strains collected over a 17-year period. The majority of these clinical strains are associated with infertility ( n = 53) and the remaining nine isolates are from gynecological infections cases. An alignment-free distance-based procedure (Jolytree) was used to infer phylogenetic relationships among M. hominis isolates, while the phylogenetic method treeWAS was used to determine the statistical association between pathotypes of interest and genotypes at all loci. Results The total pangenome of M. hominis strains was found to contain 1,590 genes including 966 core genes and 592 accessory genes, representing 60 and 37% of the total genome, respectively. Collectively, phylogenetic analyses based on WGS confirmed the distinction between the two M. hominis pathotypes. Strikingly, genome wide association analyses identified 4 virulence genes associated with gynecological infections, mainly involved in nucleotide salvage pathways and tolerance to oxidative stress, while five genes have been associated with infertility cases, two of which are implicated in biofilm formation. Conclusion In sum, this study further established the categorization of M. hominis into two pathotypes, and led to the identification of the associated genetic loci, thus holding out promising prospects for a better understanding of the differential interaction of M. hominis with its host
Bicyclic N,S-Acetals Containing Fused Cysteine-Amide System as New Heterocyclic Class Targeting Human Farnesyltransferase (FTase-h)
No full textInternational audienceWe report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence starting from the available and cost-effective L-cysteine hydrochloride (1), which is the source of N and S atoms and the chiral pool, and α-carbonyl benzoic acids (2), which are isoindolinone precursors. Concisely, the key ester intermediates (1) provide (a) sulfide-amides (4) by solvent-free amidation, (b) sulfoxides (5,6) by selective S-oxidation using NaIO4, and (c) sulfones (7) by oxidation using MMPP. Finally, the obtained N,S-acetal systems have shown promising inhibitory activities on FTase-h in the nanomolar range with excellent half maximal inhibitory concentration (IC50) values up to 4.0 nanomolar (for example, 25.1 nM for sulfide 4bI, 67.3 nM for sulfone 7bG, and more interesting of 4.03 nM for sulfoxide 5bG)
Assessment of a next generation sequencing gene panel strategy in 133 patients with negative thrombophilia screening
No full textInternational audienceAlthough heritability of venous thromboembolism (VTE) is high, the thrombophilia screening appears to be positive only in a minority of VTE patients. Adding rare variants screening to identify VTE missing heritability still requires further assessment. We report the results of a panel strategy after 3 years of application. We performed the sequencing of 28 genes related to coagulation cascade and/or VTE using high-throughput sequencing in133 unrelated patients with a personal history of VTE and negative thrombophilia screening. Only variants with minor allele frequency <0.1% were classified according to the American College of Medical Genetics recommendations. We recorded class 3, 4, and 5 variants. We identified class 3, 4, or 5 variants in 46 patients resulting in an identification rate of 35%. Out of the 45 recorded variants, 35 were considered as class 3 (78%), 9 were class 4 (20%), and 1 was class 5 (2%). Four genes accounted for nearly two-thirds (27/45) of the identified variants: SERPINC1, PROS1, F2, and F5. We observed a high rate of recurrent variants in the SERPINC1 and PROS1 genes, including the Cambridge II (SERPINC1 p.A416S), Dublin (SERPINC1 p.V30E), and Heerlen (PROS1 p.S501P) variants. The elevated frequency of these variants in a symptomatic population, compared to their frequency in the general population, provides strong support for their association with VTE risk. We identified 4 (likely) pathogenic variants in F2: p.R596Q (F2 Belgrade), p.R541W, p.P386T, and p.R425L. The high proportion of class 3 variants emphasizes the need for functional studies to better characterize and classify them
Changement climatique et risques infectieux vectoriels: Observer, comprendre, prévenir, réduire, accompagner, ou subir ?
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Total lung capacity is predictive of disease severity and survival in systemic sclerosis: A longitudinal analysis in 2347 patients from the French National Cohort Study.
No full textInternational audienceBackgroundTotal lung capacity (TLC) is seldom assessed in the prediction of systemic sclerosis (SSc) disease severity.ObjectiveTo describe and analyse TLC in SSc.MethodsWe performed a retrospective multicentre study of SSc patients enrolled in the French national SSc cohort with at least one TLC assessment, described patients based on baseline TLC measurements, modelized TLC trajectories in SSc, and associated TLC measures with disease prognosis.ResultsTwo thousand three hundred and forty-seven patients were included in the study. Baseline TLC was associated with disease severity and survival, as well as with the occurrence of interstitial lung disease (ILD), lung fibrosis (LF), and pulmonary arterial hypertension (PAH). Individual TLC trajectories varied among patients. Different models of TLC trajectories were assessed using latent process mixed models. The best model showed that the vast majority of SSc patients had stable TLC trajectories and clustered patients into three groups predictive of SSc survival, ILD, LF, and PAH. Lastly, a 10 % decrease of TLC was found to be predictive of a 5 % decrease in forced vital capacity (FVC), a 10 % decrease in DLCO, and consequently an earlier predictive marker of ILD and LF than FVC.LimitationsRetrospective study.ConclusionTLC is predictive of disease severity and survival in SSc and SSc-ILD. This work suggests TLC as an earlier risk factor for ILD and LF than FVC in SSc
Observational study of demographics and glycemia control in inpatients with type 2 diabetes: challenges and clinical implications.
No full textInternational audienceAbstractIntroductionThe objective of the present study was to evaluate the clinical, metabolic control and treatment profiles of patients with type 2 diabetes admitted to a university hospital.Research design and methodsThe study analyzed 5 years of data (2015–2020) in the University Hospital of Lille, France, focusing on stays lasting 48 hours or more for type 2 diabetes patients aged 55 or over. Stays in diabetology, outpatient and day hospital wards were excluded.ResultsAmong 2,216,834 stays during the study period, 55,292 (30%) involved diabetic patients. 50,205 (90.2%) concerned wards other than the diabetology department, and 42,865 (85.4%) of these stays involved patients with type 2 diabetes. Median [interquartile range] age was 70 years [range, 64, 79], median glycated hemoglobin level 6.8% [range, 6.1, 7.8], and median hospital stay 8 days [range, 4.3, 15.1]. A total of 55.3% of the patients treated with insulin, 40.5% with oral antidiabetic drugs, 12.5% a combination of the two, and 16.5% with lifestyle and dietary measures alone. Only 13,640 (31.8%) stays had data for glycated hemoglobin, and a third of these revealed chronic metabolic imbalance. Data on glycated hemoglobin were available for only 43.5% by patients on insulin, 51.1% for patients taking 3 oral antidiabetic drugs, and 54.9% for patients taking 4 oral antidiabetic drugs.ConclusionIt is necessary to optimize the management of people with diabetes admitted outside diabetes wards, ensuring at least HbA1c evaluation. Despite the use of various therapies, including hypoglycemic agents, few patients receive appropriate metabolic balance assessments with HbA1c as gold-standard. Optimizing collaboration between clinicians and use of clinical decision support system alerts can help in at-risk situations
Spatio-temporal risk prediction of leptospirosis: A machine-learning-based approach
No full textInternational audienceBackground: Leptospirosis is a neglected zoonotic disease prevalent worldwide, particularly in tropical regions experiencing frequent rainfall and severe cyclones, which are further aggravated by climate change. This bacterial zoonosis, caused by the Leptospira genus, can be transmitted through contaminated water and soil. The Pacific islands bear a high burden of leptospirosis, making it crucial to identify key factors influencing its distribution. Understanding these factors is vital for developing targeted policy decisions to mitigate the spread of Leptospira.Methodology/Principal findings: This study aims to establish a precise spatio-temporal risk map of leptospirosis at a national scale, using binarized incidence rates as the variable to predict. The spatial analysis was conducted at a finer resolution than the city level, while the temporal analysis was performed on a monthly basis from 2011 to 2022. Our approach utilized a comprehensive strategy combining machine learning models trained on binarized incidences, along with descriptive techniques for identifying key factors. The analysis encompasses a broad spectrum of variables, including meteorological, topographic, and socio-demographic factors. The strategy achieved a concordance metric of 83.29%, indicating a strong ability to predict the presence of contamination risk, with a sensitivity of 83.93%. Key findings included the identification of seasonal patterns, such as the impact of the El Niño Southern Oscillation, and the determination that rainfall and humidity with a one-month lag are significant contributors to Leptospira contamination. Conversely, soil types rich in organic matter may reduce bacterial presence and survival.Conclusions/Significance: The study highlights the significant influence of environmental factors on the seasonal spread of Leptospira , particularly in tropical and subtropical regions. These findings are crucial for public health planning, providing insights for targeted policies to reduce leptospirosis, while advanced machine learning models serve as a robust tool for improving disease surveillance, and risk assessment, which ultimately supports the development of an early warning system
Dog allergen-induced asthma in mice: a relevant model of T2low severe asthma with airway remodelling
No full textInternational audienceAbstract Objective and design Airway remodelling (AR) is a disabling phenomenon in patients with severe asthma, yet suitable models are lacking. We previously developed a dog allergen-induced murine asthma model characterized by T2 low Th17-driven neutrophilic airway inflammation and AR. To assess its relevance to human AR associated with T2 low severe asthma, a condition characterised by poor response to inhaled steroids, we tested the steroid sensitivity of the key features of this model. Material Asthma was induced in C57BL/6 J mice by intranasal sensitization, followed by a three-week challenge with dog allergen. Treatment : Daily intraperitoneal 1 mg kg −1 dexamethasone was administrated during the last week of challenge. Methods : We measured airway resistances in response to methacholine, cellular inflammation in bronchoalveolar lavage, lung cytokines, and quantified AR features, in response to dexamethasone. Results Dexamethasone-treated mice showed persistent airway hyperresponsiveness, neutrophilic inflammation, and Il17 a overexpression, whereas Il22 expression was abrogated. Pathological AR features, including mucus hyperproduction, subepithelial fibrosis and smooth muscle hypertrophy were not eliminated by dexamethasone. Conclusions Our dog allergen-induced murine model of asthma mirrors the steroid-insensitive traits of human severe T2 low asthma with AR, making it a relevant tool for identifying novel therapeutic targets in this orphan asthma subset