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Sodium-Glucose Cotransporter-2 Inhibitor in Diabetic and Nondiabetic Renal Transplant Recipients
No full textInternational audienceIntroduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular prognosis in patients with chronic kidney disease (CKD), diabetes, and heart failure; and slow the decline of kidney dysfunction in patients with albuminuria. Although safety and efficacy of SGLT2i have not been investigated in kidney transplant recipients (KTRs), their marketing authorization leaves the possibility of their use in these patients in France.Methods: This was a prospective multicenter real-life study including all consecutive KTRs treated with SGLT2i.Results: We identified 347 KTRs treated with SGLT2i (97% with dapagliflozin), with an initiation of treatment most often beyond the first year after transplantation (87%). Importantly, 226 (65.1%) were diabetic and 245 (70.6%) were treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). We found a low incidence of urinary tract infections (UTIs) (6.6%) and genital mycosis (0.6%), without any serious adverse event. Overall, SGLT2i were stopped in 54 patients (15.6%). The causes of SGLT2i discontinuations were very diverse. The main causes were graft dysfunction (32%), intercurrent infections (17%), urinary infections (11%), and digestive symptoms (9%). KTRs with a low estimated glomerular filtration rate (eGFR), especially those with eGFR < 30 ml/min per 1.73 m2, presented with the highest incidence of SGLT2i discontinuation (P = 0.003). SGLT2i were associated with a reduction in proteinuria, found in both diabetic and nondiabetic KTRs. In addition, they had an antihypertensive effect restricted to uncontrolled-hypertensive patients.Conclusion: SGLT2i have been used in KTRs since their authorization in France. They were discontinued more frequently in patients with impaired graft function; however, the expected side effects were infrequent and not life-threatening. The short-term antiproteinuric and antihypertensive effects are promising
Parkinson's Disease, Speech and Neurosurgery
No full textInternational audienceBackground: Speech impairment is a recognized but unpredictable adverse effect of sub-thalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD).Objectives: To evaluate the prevalence of speech impairment 1 year after STN-DBS in PD patients and to determine the predictive factors for speech outcome following STN-DBS.Methods: Data for 417 patients from the French national PREDISTIM study were collected preoperatively. The combined effect of medical treatment and surgery on speech was compared using specific items from dedicated clinical scales (MDS-UPDRS III.1: primary endpoint) and patient self-assessment questionnaires (items 34 and 35 of the PDQ39: secondary endpoints). For each variable, three patient groups were generated according to speech outcome at 1 year: worsening, stability, and improvement. In the second step analysis, the three groups were compared for demographic and clinical variables at baseline and STN-DBS parameters.Results: There was a significant deterioration in speech of all considered items 1 year after combined STN-DBS and dopaminergic treatment. Four predictive factors for speech deterioration were detected: (i) the absence of preoperative speech impairment (p < 0.001); (ii) severity of motor activity of daily living (MDS-UPDRS II off total score) (p = 0.037); (iii) high-intensity stimulation of the left electrode (i.e., above 3.6 V) (p = 0.046); and (iv) the absence of any change in non-motor experiences of daily life (MDS-UPDRS I total score) (p = 0.048).Conclusions: Speech outcome should be carefully monitored after STN-DBS, especially in PD patients without preoperative speech impairment, with motor difficulties in daily-living activities, and with increased left electrode intensity.Trial registration: ClinicalTrials.gov identifier: NCT02360683
Impact of obesity on outcomes following surgery for gastric adenocarcinoma: A European multi-institutional study
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Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma
No full textInternational audienceEfficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial
P0228 Evolution of the IBD-Disability Index in a cohort of recently diagnosed CD patients: results from the prospective CROCO (Crohn´s Disease Cohort) Study
No full textInternational audienceBackground Crohn’s disease (CD) often results in progressive bowel damage and disability. Disability has been proposed as an endpoint for disease-modification trials by the SPIRIT-IOIBD1 consensus, though data on the evolution of the IBD-Disability Index (IBD-DI) over time remain limited. Methods The Crohn’s Disease Cohort (CROCO) is a prospective, ongoing study of newly diagnosed CD patients (within 12 months of diagnosis), assessing changes in bowel damage and disability. Disability was measured using the validated IBD-Disability Index (IBD-DI), which includes 14 questions scoring from 0-100 across domains of health, sleep and energy, emotional well-being, body image, pain, defecation, interpersonal activities, and work/education. The IBD-DI was categorized as no disability (0-20), mild disability (21-35), moderate disability (36-50) and severe disability (51-100). We examined changes in the IBD-DI from baseline to the second year of follow-up. Results Among 394 patients recruited, 105 had complete IBD-DI data at incluision and at 24 months. The cohort was 54% male, with a median age at diagnosis of 35.5 years (IQR 24.9-47.9). Median time from symptom onset to diagnosis was 6.1 months (IQR 2-20), with a disease duration of 8.2 months (IQR 4.6-10.3) at study entry. Table 1 summarizes disability categories at baseline, year 1, and year 2. Between baseline and year 2, disability decreased in 30% of patients, remained stable in 48%, and increased in 23% (Figure 1). Changes in IBD-DI were significantly associated with gender (p=0.004) and symptoms (Harvey-Bradshaw index) at baseline (p=0.002), but not with extra-intestinal manifestations (EIM), therapies, or surgical history. Among patients with bowel resection within the 1st year of diagnosis, IBD-DI decreased in 50%, remained unchanged in 43%, and increased in only 7% between baseline and year 2 (p= 0.15). Starting an advanced therapy within the 1st year after diagnosis did not impact IBD-DI evolution between baseline and year 2 (p= 0.92). Conclusion Our findings show the evolution of disability in newly diagnosed CD patients highlighting that IBD-DI is able to change in more than half of the patients within the first two years after diagnosis. While disability improved in almost 1/3 of patients, 1/4 of patients still experience moderate-to-severe disability after 24 months. References 1 Le Berre, C., Peyrin-Biroulet, L., Sandborn, W. J., Colombel, J. F., Rubin, D., Chowers, Y., ... & Danese, S. (2021). Selecting end points for disease-modification trials in inflammatory bowel disease: the SPIRIT consensus from the IOIBD. Gastroenterology, 160(5), 1452-1460
Chromosomal abnormalities in oocyte donor candidates: a French survey of over 8200 karyotypes
No full textInternational audienceObjective: To study karyotypes of more than 8,200 oocyte donor candidates in nulliparous or multiparous women compared to a reference population.Design: A retrospective observational multicentric study.Subjects: The study included two cohorts of oocyte donor candidates recruited between January 2005 and October 2021: multiparous women with at least one child at the time of recruitment, and nulliparous women. Both were compared to a reference population composed of female newborns from literature.Exposure: Not applicable.Main outcome measures: Blood lymphocyte karyotype.Results: A total of 8229 oocyte donor candidates from 22 fertility centers were included in this study. Nulliparous women (n=1890) and multiparous ones (n=6339) were compared to 8102 female newborns. Overall, 65 candidates were carriers of chromosomal abnormalities and were therefore excluded from the donation process (0.79%, 95% CI: 0.60-0.98). The occurrence of balanced structural chromosomal rearrangements was globally increased in the study population (0.49%, 95% CI: 0.34-0.64) compared to female newborns (0.24%, 95% CI: 0.34-0.64, p=0.0086). The number of reciprocal translocations was increased 5-fold in nulliparous oocyte donor candidates (0.37%, 95% CI: 0.10-0.64, p=0.013). The incidence of sex chromosome mosaicism was notably increased in multiparous oocyte donor candidates, with 17 cases (0.27%, 95% CI: 0.14-0.40, p=0.0052). Among chromosomal aberration carriers only two nulliparous women (one reciprocal translocation and one sex chromosome mosaicism) had fertility issues with a diagnosis of premature ovarian failure.Conclusion: In this comprehensive 16-years French experience of karyotyping in oocyte donor candidates, we confirmed an increased incidence of balanced structural chromosomal rearrangements, especially among those without children at the time of recruitment. Karyotyping could be considered to identify any chromosomal abnormalities that may not be easily detectable through medical questioning. These abnormalities pose an inherent genetic risk for gamete recipients if left undetected
Flowers for Algernon: How Metacognition Affects Quality of Life in Schizophrenia. Structural Equation Modeling with the Face-Sz Cohort
No full textInternational audienceBackground and HypothesisWe examined the association between metacognitive performance, functioning, and quality of life (QoL) in schizophrenia using structural equation model analyses.Study DesignA sample of 249 participants was assessed for symptoms, functioning, QoL, and both objective and subjective cognitive performance. Metacognitive performance was defined as the adequation between objective and subjective measures of cognitive performance.Study ResultsOur model showed an excellent fit (CFI = 0.981; RMSEA = 0.014–0.081) and explained 53.3% of the variance in functioning and 50.3% in QoL. Metacognitive performance was not significantly associated with functioning but showed a negative association with QoL (β = -0.383, p < 0.001). Thus, a greater underestimation of one’s cognitive abilities was linked with lower QoL, potentially reflecting heightened awareness of deficits that affect well-being. Depression, also negatively associated with QoL (β = -0.359, p < 0.001), was linked to the underestimation of cognitive abilities, whereas symptom severity was associated with their overestimation (β = -0.296, p < 0.001). Complementary analyses suggest that the subjective cognition model closely mirrors that of metacognitive performance, questioning the distinctiveness of metacognition as an explanatory factor in schizophrenia outcomes.Conclusion Our findings imply that interventions that boost confidence in cognitive abilities, such as cognitive remediation, may improve QoL. Future research should investigate the causal pathways between these factors and explore the role of social cognition, often impaired in schizophrenia, as another mediator. Comprehensive treatment that addresses clinical symptoms, depression, and subjective cognition challenges appear essential to improve outcomes in schizophrenia
Prise de décision des mères au sujet de la parentalité : les défis de l'influence de l'entourage
No full textIntroduction: this study aimed to assess the impact of the social environment on mothers’ parenting decisions during the first six months postpartum. Methods: an observational study was conducted among 333 mothers of infants under six months, through an online questionnaire. Results: 66% of first-time mothers changed at least one decision due to social influence. 28.3% reported doubts caused by unsolicited advice. Perceived support increased confidence, while first-time mothers, more exposed, showed lower confidence (p=0.006). The most challenging decisions involved sleep, family organization, and feeding. Partners (26%) and healthcare professionals (22.6%) were the main sources of support. Overall, 94.8% perceived a low to moderate influence from their social circle. Discussion: the social environment has an ambivalent role—supportive yet sometimes pressuring. Enhanced postpartum support could foster maternal autonomy. Conclusion: the social circle influences parenting decisions, especially among first-time mothers. Tailored support could improve maternal confidence.Introduction : cette étude visait à évaluer l’impact de l’entourage sur les décisions parentales des mères durant les six premiers mois post-partum. Méthode : une étude observationnelle a été menée auprès de 333 mères d’enfants de moins de six mois, via un questionnaire en ligne. Résultats : 66 % des primipares ont modifié au moins un choix sous l’influence de l’entourage. 28,3 % ont exprimé des doutes liés aux conseils non sollicités. Le soutien perçu renforce la confiance, tandis que les primipares, plus exposées, montrent une confiance moindre (p = 0,006). Les décisions les plus complexes concernaient le sommeil, l’organisation familiale et l’alimentation. Le partenaire (26 %) et les professionnels de santé (22,6 %) étaient les soutiens principaux. 94,8 % des femmes perçoivent une influence faible à modérée de leur entourage. Discussion : l’entourage a un rôle ambivalent, entre soutien et pression. Un accompagnement post-partum renforcé favoriserait l’autonomie des mères. Conclusion : l’entourage influence les décisions parentales, particulièrement chez les primipares. Un soutien adapté pourrait renforcer leur confiance
Concordance between presenting features and relapse in granulomatosis with polyangiitis: implications for risk assessment and counselling
No full textInternational audienceObjective: To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse.Methods: Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression.Results: Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse.Conclusion: Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ
