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Impact of endometriosis on the progression of inflammatory bowel diseases: a multicenter retrospective study
No full textInternational audienceIntroduction: Women with endometriosis have a higher risk of developing inflammatory bowel diseases (IBD). This study aimed to better understanding the impact of endometriosis on the course of IBD. Methods: We conducted a retrospective cohort study in 18 French and Belgian IBD centers between June 2022 and March 2023. Any patient with both conditions was eligible for inclusion. They were randomly matched to 1 or 2 patients with IBD without endometriosis. The impact on IBD progression was assessed using a composite severity criterion including intestinal damage or need for bowel surgery. Results: Overall, 207 patients with both conditions (149 Crohn's disease (CD); 58 ulcerative colitis (UC)) were matched to 409 patients with IBD alone. The median follow-up duration for IBD was 10 years [5.75-17]. No difference was observed between the two groups regarding CD location, disease phenotype, and anoperineal involvement. Proctitis were more frequent in patients with UC and endometriosis. IBD patients with endometriosis were significantly less exposed to immunosuppressants (UC p<0.01; CD p<0.001) and biologics (UC p<0.01; CD p<0.001). CD patients with endometriosis had a less severe disease course compared to patients without endometriosis (HR=0.68; 95%CI 0.50-0.92; p=0.011). UC patients with endometriosis had not a significant different disease course compared to patients without endometriosis (HR=1.73; 95%CI 0.74-4.00; p=0.20). These results were similar in the subgroup of patients with endometriosis treated surgically. Conclusions: Endometriosis does not negatively influence the course of IBD, patients with CD even have a less severe progression. Patients were significantly less exposed to immunosuppressants and biologics
Pediatric Growth Patterns of the Circle of Willis: Systematic Review and Implications for Clinical Neurovascular Applications
No full textInternational audienceBACKGROUND AND OBJECTIVES: The Circle of Willis (CoW) ensures cerebral perfusion and collateral support, yet pediatric CoW growth is poorly described compared to adults. Clarifying its developmental trajectory is essential to optimize planning and execution of endovascular/surgical procedures. This systematic review assesses pediatric CoW development, identifies gaps in current knowledge, and explores the implications for future diagnostics and interventions. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, databases including PubMed, ClinicalTrials.gov, Cochrane Library, ScienceDirect, Web of Science, and Medline were searched using terms such as Circle of Willis, intracranial arteries, cerebrovascular system, children, growth, development, and pediatric cerebrovascular development . Articles from January 1987 to September 2024 were screened. RESULTS: Of 513 articles identified, 3 met inclusion criteria, totaling 608 pediatric subjects. All studies described a biphasic growth pattern, rapid arterial expansion during infancy followed by slower growth, and demonstrated strong correlations between vessel dimensions and head circumference. Children exhibited greater CoW symmetry and fewer anatomic anomalies than adults, challenging the assumption that vascular configurations stabilize or improve only with age. This suggests that factors driving asymmetry in adulthood, environmental, hemodynamic, or structural, warrant further study. CONCLUSION: Pediatric CoW development follows a tightly regulated, region-specific timetable linked to skull and brain maturation. However, small sample sizes, uneven age distributions, and limited longitudinal data constrain current insights. Future research should use 4D flow MRI, balanced longitudinal cohorts, and integrated geometric–hemodynamic assessments, and explore correlations with other cerebral structures to improve early detection of anomalies and guide targeted endovascular and surgical interventions in pediatric cerebrovascular care
Dosimetric impact of iodinated contrast agent on planning CT for volumetric-modulated radiotherapy of head and neck cancer
No full textInternational audiencePurpose: Volumetric-modulated arc therapy for head and neck cancers requires accurate delineation of target volumes and organs at risk. Iodinated contrast agents enhance visualization, but their impact on dose distribution remains a concern. Traditionally, dosimetry is performed on non-contrast CT scans to minimize dose calculation discrepancies. This study evaluates the dosimetric impact of planning directly on contrast-enhanced CT scans.Material and methods: Twelve patients with head and neck cancers (oral cavity, oropharynx, pharyngolarynx, ethmoid, thyroid) treated using volumetric-modulated radiation technique were included. Target and organs at risk delineation and dose calculation were performed on contrast-enhanced CT scans and subsequently transferred to non-contrast CT scans without renormalization. Prescribed doses for high-risk planning target volume were 60 to 70Gy, for low-risk planning target volume 54Gy, in 30 to 33 fractions. Volumetric-modulated arc therapy planning was performed on Eclipse® (version 15.6), with simultaneous integrated boost, using the AAA dose calculation algorithm. Dosimetric variations in organs at risk and planning target volumes were assessed.Results: Mean variations of mean dose for organs at risk mandible, larynx, parotid glands, and pharyngeal constrictor muscle ranged from 0.02Gy (0.10 %) to 0.16Gy (0.38 %). Mean D2 % variations for spinal canal, brainstem, brachial plexus, and carotid arteries ranged from 0.05Gy (0.17 %) to 0.16Gy (0.46 %). None of the variations for organs at risk were found to be statistically or clinically significant. For planning target volumes, variations in coverage by the 95 % isodose of the prescribed dose were always less than 1 %. The maximum variation of maximum dose was a decrease of 0.6Gy, representing 0.8 %.Conclusion: Performing volumetric-modulated arc therapy planning directly on contrast-enhanced CT scans leads to minimal dosimetric variations (less than 1 %) compared to non-contrast CT scans. This approach could streamline clinical workflows by eliminating the need for dual CT acquisitions and optimizing treatment preparation
Chemotherapy‑induced peripheral neuropathy in patients with breast cancer treated with taxanes (Review)
No full textInternational audienceBreast cancer is the most common malignancy among women worldwide and is frequently treated with taxane-based chemotherapy. Despite their therapeutic efficacy, taxanes are associated with a high incidence of chemotherapy-induced peripheral neuropathy (CIPN), a disabling condition that impacts the quality of life of patients. CIPN primarily affects the sensory nerves, leading to symptoms such as numbness, tingling, pain and motor dysfunction, which can persist long after treatment completion. The pathophysiology of taxane-induced CIPN involves direct neurotoxic effects on the dorsal root ganglia, a disruption of microtubule dynamics and neuroinflammatory responses. Given the limited efficacy of current pharmacological treatments, such as duloxetine, lidocaine or topical agents, alternative approaches, including cryotherapy and other non-pharmacological interventions, are being explored. The present literature review provides an updated synthesis of the epidemiology, mechanisms and management strategies of taxane-induced CIPN among patients with breast cancer. Identifying efficacious interventions remains a critical challenge in oncology. By specifically addressing this underexplored, yet clinically relevant, issue, the present review aims to promote future improvements in patient care and quality of life
Male and female workers suffering from chronic low back pain display different interrelationships between the biopsychosocial variables
No full textInternational audienceObjective: To study the biopsychosocial model of chronic low back pain in the workplace and the role of sex in it.Design: Cross-sectional nationwide survey in a service company.Patients: 256 workers (women 64.1%) reporting chronic low back pain.Methods: Variables on biometry, job description, physical activity, pain severity/interference, neuropathic features, and questionnaire-based cognitive and affective parameters were collected. Within each sex group, the interrelationships between variables by Multiple Correspondence Analysis were analysed, followed by cluster analysis.Results: In the overall sample, neuropathic features were reported by 28.9% of the patients; the cluster including the high pain disorder modalities (i.e., severity and interference) also included high pain catastrophizing and fear/avoidance towards work, as well as neuropathic features. However, in men, the modalities neighbouring high pain disorder were high anxiety and depression, and low mental quality of life, while in women, they were kinesiophobia, high fear/avoidance towards physical activity and stress at work, and low physical quality of life.Conclusion: As there is now a major demand for defining chronic low back pain patients based on their biopsychosocial profile to improve care and prognosis, this study’s results indicate the relevance of conducting such phenotyping at an early stage in a working environment, and that it is preferable to construct predictive models for each sex grou
Designing DECIdE Together: An Interprofessional and Patient-Centered Approach to Develop a Patient Decision Aid for Drugs in Primary Care (DECIsion in hEalth)
No full textInternational audienceBackground. In primary care, general practitioners (GPs) and community pharmacists (CPs) play pivotal roles in guiding patients’ drug choices. Nonprescription drugs (NPDs), which are dispensed with or without a prescription, represent significant health care costs. NPDs are most often used for symptomatic relief and may be subject to shared decision making. We designed shared DECIsion in hEalth (DECIdE), a patient decision aid for NPDs in primary care, via a 3-step user-centered approach. Design. In the first step, a nominal group composed of potential future users (patients, GPs, and CPs) reached a consensus on the prototype’s specifications. In the second step, GPs, CPs, and their patients tested the prototype in user tests during simulated consultations based on real-life scenarios, and clinical psychologists conducted individual interviews to improve the prototype. In the third step, international experts used the eDELPHI consensus method to validate DECIdE as a shared decision aid. Results. Sixteen participants in the nominal group reached a consensus on 18 specifications. The user tests involved 16 patients and 4 health care professionals across 2 cycles. The prototypes were improved according to an analysis of 20 individual interviews. Fifteen French-speaking experts, searchers, physicians, and pharmacists from 4 countries reached a consensus on 11 of the 13 propositions inspired by the IPDAS criteria and the French HAS criteria in 2 rounds to validate the final prototype of DECIdE. Conclusion . Interprofessional collaboration at each step of development is the main strength of this user-centered design. DECIdE is currently being evaluated for its effects on decisional conflict in GPs’ practices and community pharmacies in a randomized controlled trial. Implications. DECIdE could encourage more rational use of NPDs, particularly in self-medication. Highlights DECIdE is the first patient decision aid in French for usual drugs in primary care, based on the latest scientific data in line with an evidence-based medicine approach for general practitioners (GPs) and community pharmacists (CPs). DECIdE’s user-centered design includes interprofessional collaboration at each step between searchers, GPs, CPs, and social and clinical psychologists. The original 3 steps of the user-centered design of DECIdE combined user testing with qualitative analysis and 2 successive consensus methods to create and validate the patient decision aid using the nominal group and eDELPHI methods. The free availability of DECIdE on a dedicated Web site will enable GPs and CPs to make widespread use of shared decisions about nonprescription drugs daily
Efficacy and Safety of NFL-101 as a Smoking Cessation Therapy: A Randomized Phase II Clinical Trial CESTO2
No full textInternational audienceIntroduction: Tobacco addiction remains a major public health challenge. Existing smoking cessation treatments require prolonged daily use with potentially poor adherence and reduced efficacy.Methods: The phase II study was a multicenter, randomized, double-blind, placebo-controlled trial with a one-year follow-up to assess the efficacy, safety, and immunogenicity of NFL-101 as a potential aid for smoking cessation. 318 adult daily smokers were randomized to receive subcutaneous injections of NFL-101-100 μg, NFL-101-200 μg or placebo on Day1 and Day8. The primary outcome was 6-week post-quit 28-day continuous abstinence (CA, Day15-Day43), validated by exhaled CO.Results: CO verified 6-week post-quit CA was: NFL-101-100 μg: 31/108(28.7%), 200 μg: 23/109(21.1%), and placebo: 18/101(17.8%). NFL-101-100 μg vs placebo, RR = 1.61, p=.063, and 200 μg vs placebo RR = 1.18, p=.5492). CA, when urinary cotinine was used, was: 26/108(24.1%) for NFL-101-100 μg, 18/109(16.5%) for 200 μg and 13/101(12.9%) for placebo. NFL-101-100 μg vs placebo showed an RR = 1.87, 95%CI:1.02-3.44, p=.0378 and 200 μg vs placebo was RR = 1.28, 95%CI:0.66-2.48, p=.4572. If individuals who used NRTs/e-cigarettes were classified as non-abstinent, then 29/108(26.9%) were abstainers for NFL-101-100 μg and 14/101(13.9%) for placebo (p=.0203). NFL-101-100 μg RR remained stable between 28-day and 12-month. At Day43, NFL-101-100 μg reduced craving (p<.05), with no significant difference for withdrawal symptoms. Abstainers experienced greater increases in anti-NFL-101-IgG concentrations compared to nonabstainers (p<.009). NFL-101 was well-tolerated.Conclusions: Although the pre-specified primary endpoint was not statistically significant, if the primary outcome had been defined as nicotine abstinence, the results would have reached statistical significance. Efficacy, craving reduction and minimal dosing regimen of NFL-101-100 μg support its potential as a promising smoking cessation therapy.Implications: In this multicenter randomized clinical trial that included 318 smokers, effect sizes between groups were sufficiently large to suggest a meaningful clinical effect. NFL-101 at a dose of 100 μg increased 6-week post-quit 28-day continuous smoking abstinence that was confirmed by urinary cotinine concentrations and reduced craving, suggesting psychological benefits that could mitigate relapse risks. Abstainers experienced a significant increase in anti-NFL-101 IgG concentrations compared to those who continued to smoke.Findings from the present study offer support for an entirely new category of treatment that acts through immune modulation. Additional strengths include a subcutaneous route of administration in the form of two injections spaced a week apart (thus, enhances treatment adherence) and has demonstrated a safe profile with minimal adverse effects. These results support a follow up Phase III clinical trial.Trial registration: ClinicalTrials.gov identifier: NCT04571216
PErsistence and safety of subcutaneous infliximab 1 year after switch from intravenous route in IBD patients in REMission
No full textInternational audienceBackground and aim: Real-life data regarding Inflammatory Bowel Disease (IBD) evolution after switch from intravenous (IV-IFX) to subcutaneous infliximab (SC-IFX) is necessary. The aim of this prospective multicenter cohort study was to describe the persistence, effectiveness and tolerance of SC-IFX after switch from IV-IFX.Methods: IBD patients in steroid-free clinical remission for at least 6 months on IV-IFX, were enrolled in a prospective national French cohort when they switched to SC-IFX. Patients were assessed at inclusion and at weeks (W) 12, 24 and 48. Primary endpoint was the persistence of SC-IFX at W48. Secondary endpoints comprised steroid-free clinical remission at W48, IV-IFX switch-back rate, and evolution of infliximab levels during the study period.Results: Among the 426 patients included (72.4% with Crohn's disease (CD), 27.5% with ulcerative colitis (UC); 45.1% females; median age 37 [29-50] years; median disease duration of 12 years in CD, 13 years in UC), 56% were on IV-IFX standard dosing (5mg/kg 8-weekly) and 16% received combination therapy with an immunomodulator drug at baseline. At W48, SC-IFX persistence was 95.4% (95%CI, 93.3-97.5) and 86.9% of patients were on steroid-free clinical remission. Mean infliximab levels were 8.0μg/mL at inclusion and 18.0 μg/mL at W48 (p<0.0001). Among the 19 (4.5%) patients who stopped SC-IFX, 6 (1.4%) switched back to IV-IFX. There were 222 adverse events reported in 42.4% of patients, 12 led to treatment discontinuation, including six (1.4%) severe adverse events.Conclusion: In this large multicenter prospective cohort, persistence at one year of SC-IFX was more than 95% of IBD patients switched in remission from IV-IFX, confirming excellent effectiveness and tolerance of SC-IFX
Vat-Mediated Mucus Penetration Enables Genotoxic Activity of pks+ Escherichia coli
No full textInternational audienceColibactin toxin-producing Escherichia coli (pks+ E. coli) strains are associated with the occurrence of colorectal cancer in humans. These strains induce DNA damage when in close contact with the cells of the intestinal epithelium. Therefore, maintaining the integrity of the mucus layer that covers the intestinal epithelial mucosa is crucial for counteracting the effects of colibactin. The Vat protein is a mucin protease capable of degrading MUC2 mucus proteins that was previously described in adherent and invasive Escherichia coli strains. Our work shows that the vat gene is found in the genome of all pks+ E. coli strains isolated from patients with colon cancer. In mucus-producing HT29-16E cells, we demonstrated that the Vat protein of E. coli pks+ allows bacteria to penetrate mucus and to reach the epithelial cells. Cells infected with the E. coli pks + vatstrain show a reduction in γ-H2AX staining, a marker of DNA damage. Infection of Apc Min/+ mice with the E. coli pks + vat+ strain or the E. coli pks + vatmutant revealed that Vat enhances the ability of pks+ E. coli strains to colonize the intestinal mucosa and, in turn, their pro-carcinogenic effects. This study reveals that Vat promotes crossing of the intestinal mucus layer, gut colonization, and the carcinogenicity of pks+ E. coli
