Bronchiolitis is a common condition caused by a viral acute lower respiratory infection (ALRI) in infants. Severe bronchiolitis requiring hospitalisation is associated with increased risk of preschool wheeze and school-age asthma. Early exposure to microbial products modulating immune system development may help prevent later wheeze. Thus, this study evaluates whether an oral bacterial lysate after bronchiolitis hospitalisation reduces subsequent wheezing episodes. This international multicentre, randomised, double-blind, placebo-controlled trial tests bacterial lysate (OM85-BV; Broncho-Vaxom®) in infants after hospitalisation for bronchiolitis. Safety and efficacy will be assessed, and a subset will undergo exploratory mechanistic analyses. For 12–24 months post-discharge, parents/guardians will give one capsule of OM85-BV or placebo daily for 10 consecutive days each month. The primary endpoint is the number of parent/guardian-reported wheeze episodes 12-months after starting OM85-BV or placebo. Secondary outcomes at 12 or 24-months follow-up include clinical outcomes, parent-proxy quality-of-life scores, incidence of atopy, recurrent wheeze needing asthma medication, wheeze-related hospitalisations, number of ALRI episodes, and mechanistic data on systemic immune pathways and nasopharyngeal and gut microbiota. This international multicentre study will determine whether oral OM85-BV given for 10 consecutive days each month for 12–24 months reduces parent/guardian-reported recurrent wheeze episodes post-hospitalisation for bronchiolitis. AZNCTR ACTRN12621001556831 (5/10/2021) and clinicaltrials.gov NCT05064631 (20/08/2020). Prospectively Registered. Approval to use the IMP in this clinical trial was provided by the Australian Government Therapeutic Goods Agency under the clinical trials notification scheme (TGA CTN: CT-2021-CTN-02639-1).
Infants undergoing enterostomy for necrotizing enterocolitis (NEC) are at high risk of intestinal failure-associated liver disease (IFALD). Early identification of high-risk infants remains challenging. This study aimed to develop and validate an early prediction model for IFALD using routinely available perioperative variables. This retrospective study included 388 infants who underwent enterostomy for NEC between November 2019 and November 2024. Clinical, nutritional, and laboratory variables were collected. Boruta and least absolute shrinkage and selection operator (LASSO) regression were used for feature selection. Logistic regression, LASSO regression, random forest, naïve Bayes, and partial least squares (PLS) models were compared using discrimination, classification metrics, calibration, and decision curve analysis. Shapley additive explanations (SHAP) were used to interpret the final model. Among 388 infants, 103 (26.5%) developed IFALD. The training cohort comprised 273 infants (73 IFALD and 200 non-IFALD), and the validation cohort comprised 115 infants (30 IFALD and 85 non-IFALD). Infants with IFALD had lower gestational age, lower birth weight, shorter residual bowel length, delayed enteral nutrition recovery, and longer parenteral nutrition (PN) dependence. The random forest model showed the best validation performance, with an area under the receiver operating characteristic curve of 0.805 (95% confidence interval, 0.719–0.891), sensitivity of 0.700, specificity of 0.765, and accuracy of 0.748. SHAP analysis identified birth weight, residual bowel length, age at admission, preoperative systemic immune-inflammation index, postoperative platelet-to-lymphocyte ratio, and central venous catheter infection as the most important predictors. Infants with enterostomy after NEC surgery often need prolonged PN, which increases the risk of IFALD. This study built an early prediction model using routine perioperative data. The random forest model showed good discrimination and high sensitivity, and may help clinicians identify infants who need closer liver monitoring, careful PN management, and infection prevention.
Evidence linking the inflammatory burden index (IBI) to sex hormone profiles during development remains limited. Multivariable linear regression was used to examine associations between IBI and testosterone, estradiol, and sex hormone-binding globulin (SHBG). Restricted cubic spline analyzes (RCS) assessed nonlinear relationships. Stratified and sensitivity analyzes were performed. After full adjustment, higher IBI was associated with lower testosterone (β = –0.143, 95% CI: –0.190 to –0.096) and, among adolescents, lower estradiol (β = –0.113, 95% CI: –0.155 to –0.071). Participants in the highest IBI quartile had markedly reduced testosterone (β = –0.587, 95% CI: –0.807 to –0.366) and, among adolescents, estradiol (β = –0.477, 95% CI: –0.684 to –0.270). For SHBG, significant inverse associations were observed in the second and third IBI quartiles. RCS analyzes showed a nonlinear inverse association with testosterone, a nonlinear inverse association with estradiol among adolescents, and a U-shaped relationship with SHBG. Stratified analyzes suggested potential differences in associations across developmental stages and sexes. Results were robust in sensitivity analyzes. Higher IBI was associated with lower testosterone in children and adolescents and lower estradiol among adolescents, whereas SHBG showed a U-shaped association. Further prospective studies are needed to clarify temporality and clinical relevance.
Rationale Validated thresholds for clinically meaningful change in quantitative computed tomography (QCT) for fibrosis extent across algorithms remain unclear in idiopathic pulmonary fibrosis (IPF).Objectives To evaluate minimal clinically important difference (MCID) for 1-year change in QCT metrics in IPF using different algorithms than previously reported and to identify prognostically meaningful thresholds for effective risk stratification. Methods This multicenter retrospective study included IPF patients with baseline and 1-year follow-up CT. Minimal clinically important differences for change in fibrosis score (Delta FS) derived from fully automated CT quantification were estimated using an anchor-based approach with 1-year changes in FVC and diffusing capacity for carbon monoxide (DLco), and a prognostic threshold was estimated using maximally selected log-rank statistics. Prognostic significance of Delta FS was evaluated in discovery and validation cohorts. Results The discovery cohort included 524 patients (mean age = 66.8 years; 79% men), and the external validation cohort included 224 patients (mean age = 69.6 years; 83% men). Anchor-based MCIDs were 2.72% for FVC and 4.52% for DLco, with a prognostic threshold of 4.05%. In the discovery cohort, 1-year Delta FS were independently associated with transplant-free survival (TFS), with greater risk when Delta FS exceeded MCID or prognostic thresholds (all, P < .001). In the validation cohort, Delta FS remained associated with TFS (adjusted hazard ratio [aHR] = 1.11; 95% CI, 1.04-1.18), and all prespecified Delta FS thresholds were prognostic for overall TFS, with the prognostic threshold of Delta FS >= 4.05% showing the most consistent associations with overall (aHR = 2.78; 95% CI, 1.36-5.68) and 3-year TFS (aHR = 2.88; 95% CI, 1.11-7.48). Conclusion One-year change in FS and its thresholds were significantly associated with TFS, supporting annual CT follow-up with predefined QCT thresholds for monitoring and risk stratification in IPF.
