Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment.

BACKGROUND: Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined as difficult-to-treat IBD. AIM: The objective of this study was to investigate for the first time the treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy. METHODS: We reviewed all consecutive patients with IBD treated at the Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy. RESULTS: We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis, the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p > 0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that the persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks, respectively, p = 0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks, respectively, p = 0.035). In multivariate regression, Crohn's disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence. CONCLUSION: In this first real-world setting, risankizumab could have a longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn's disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.

Impact of corticosteroid exposure on preterm labor in neonates eventually born at term.

OBJECTIVE: To evaluate the impact of antenatal corticosteroid therapy (ACS) on birth outcomes in term infants exposed during pregnancy. STUDY DESIGN: Exposed newborns were compared with non-exposed controls in a 1 to 2 design. Multivariate analysis was used to assess the effect of ACS exposure on neonatal outcomes. RESULT: 408 newborns were included (136 exposed to ACS, 272 non-exposed). Mean ± SD head circumference (HC) was 33.7 ± 1.4 vs 34.3 ± 1.6 cm, p = 0.001 in exposed vs controls; birth weight was 3.1 ± 0.4 vs 3.3 ± 0.4 kg, p = 0.0001; and birth height was 47.9 ± 2.1 vs. 49.1 ± 2.0 cm, p < 0.0001. Hypocalcemia (4.4 vs 0.7%, p = 0.019) and feeding difficulties (5.1 vs 1.5%, p = 0.047) were significantly more common in exposed newborns. Multivariate analysis for HC showed a significant independent association with ACS exposure (ß = -0.5, p = 0.009). CONCLUSION: Term newborns exposed to ACS have lower birth HC and higher risk of neonatal complications. CLINICAL TRIAL REGISTRATION: NCT05640596.

Prognostic indicators in pituitary adenoma surgery: a comprehensive analysis of surgical outcomes and complications.

Objective: The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success. Methods: A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis. Results: Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004). Conclusion: This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management.

Inflammatory Bowel Disease Patients' Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience.

BACKGROUND: Subcutaneous infliximab and vedolizumab formulations have been developed for maintenance therapy in inflammatory bowel disease. The objective of this study was to explore the inflammatory bowel disease patient's acceptance for switching from intravenous infliximab or vedolizumab to subcutaneous, as well as to describe the causes of refusal or, conversely, the factors associated with acceptance. METHODS: Patients were prospectively recruited between June 2021 and March 2022 during their infusion of infliximab or vedolizumab in the Medical Day Hospital of Nancy University Hospital. Adult patients with an established diagnosis of inflammatory bowel disease in clinical remission were eligible for inclusion in this study if they had been treated with intravenous infliximab or vedolizumab for at least six months. RESULTS: One hundred and thirty patients were included in this study. Thirty-six patients (27.7%) received vedolizumab and ninety-four patients (72.3%) received infliximab. Median duration of treatment at inclusion was 7.0 years [3.0-11.0]. In this cohort, 77.7% of patients accepted the switch from intravenous infliximab or vedolizumab to subcutaneous. The main reasons for patient's refusal for switching from intravenous to subcutaneous formulation were fear of loss of efficacy, a more spaced-out medical follow-up, increased frequency of administration, and self-administered injection. A short duration of treatment was associated with a high switch acceptance rate (odd ratio (OR) (95% confidence interval (CI)) = 0.9 (0.8-0.9); p = 0.0002). CONCLUSION: A large majority of the patients included accepted the switch of their treatment with infliximab or vedolizumab from the intravenous form to the subcutaneous form. This study identified one predictor influencing the acceptance rate in inflammatory bowel disease population: short treatment duration. Subcutaneous infliximab and vedolizumab hold potential for greater patient flexibility by self-administration, reducing travel and hospital attendance for infusion.

Factors Associated with Discrepancy of Child-Adolescent/Parent Reported Quality of Life in the Era of COVID-19.

Billions of children/adolescents experienced unprecedented changes in their daily lives that impacted their health-related quality of life (HRQoL) during the first wave of the coronavirus disease 2019. The purpose of this study was to describe child-parent discrepancies in reporting on HRQoL and explore factors associated with such discrepancies at the end of the first lockdown in France. A cross-sectional study was conducted among French school-aged children from 8 to 18 years and their parents living in the Grand Est region in France during the first wave of the epidemic. The impact of individual, self-reported health status and environmental data on discrepant parent-child reports of HRQoL was assessed by multinomial multivariable logistic regression models. A total of 471 parent-child pairs were included. Among 50% of the discordant pairs, parents underestimated HRQoL more frequently than they overestimated it. Home location, social support score, children's education level, parents' education level, tensions and conflicts with neighbors reported by children, whether they had access to a garden, and parents' professional activity were significantly associated with parental overestimation (adjustedOR from 2.08 to 11.61; p < 0.05). Factors associated with parental underestimation were children's education level, SF12 score, home location, the child's gender, parent's level of education, the presence of noise in the residence reported by children, whether a household member was infected with COVID-19, whether they had access to a garden, and family structure (adjustedOR from 1.60 to 4.0; p < 0.05). This study revealed differences between child-reported and parent-reported HRQoL. The COVID-19 pandemic accentuated the discrepancies in observable dimensions and attenuated them in unobservable dimensions of HRQoL but did not impact the directional discrepancy; parents underestimated their child's HRQoL more. These discrepancies appear to be explained by parent and child sociodemographic factors.