Background: Milk ladder (ML) is considered a potential therapeutic option for managing cow’s milk allergy (CMA). Although the ML was initially developed to reintroduce cow's milk into the diet for individuals with non‐IgE mediated CMA, it has also recently been used in IgE‐mediated CMA. Objective: To perform a systematic review and meta‐analysis of the safety and efficacy of ML in children with IgE‐mediated milk allergy. Methods: We conducted a systematic literature review and meta‐analysis of controlled studies in accordance with PRISMA guidelines. ML safety and ML efficacy compared to a strict avoidance diet and oral immunotherapy in children with IgE mediated CMA was evaluated. Meta‐analysis was performed where ≥ 3 studies reported data. Methodological quality and risk of bias were systematically assessed. Results: Six controlled studies (two randomized controlled trials and four observational controlled studies) met the inclusion criteria. ML resulted in the development of tolerance in 69% of participants (OR = 4.48; 95% CI = 2.51–8.00), with a significant improvement compared to the elimination diet. The meta‐analysis of four studies showed that ML was 4.5 times more effective than a strict avoidance diet in inducing partial or total tolerance in ITT analysis and 8.4 times in PP analysis. Certainty of evidence was moderate, with low heterogeneity among studies. No significant difference in adverse events, severe systemic allergic reactions, and adrenaline use between the ML and avoidance diet groups were found. Only one study reported comparable efficacy between ML and oral immunotherapy with raw milk (OIT). No difference was found in the total number of mild to moderate adverse reactions between the groups (68.2% and 77.8, respectively; p = 0.44). The rates of epinephrine use at home were 14.3% and 11.8%, respectively, without significant difference between ML and OIT groups ( p = 1). Conclusions: ML represents a promising therapeutic approach for accelerating tolerance in children with IgE‐mediated CMPA. Further research is needed to clarify milk ladder safety, as well as to identify predictive biomarkers for patient selection.

Background: Survivors of childhood brain cancer survivors (CBCS) have a higher risk of endothelial dysfunction and cardiovascular mortality. Recombinant human growth hormone (rhGH) replacement therapy may help reduce endothelial damage and the development of cardiovascular diseases (CVD). This study aimed to assess biochemical and biophysical endothelial function in CBCS with GH deficiency (GHD). Methods: CBCS who were at least two years post-treatment underwent clinical evaluation, including anthropometric measurements and metabolic assessments (adiponectin, blood clotting, and lipid profile). Endothelial function was evaluated using the estimation of the reactive hyperemia index (RHI) measured by the EndoPAT 2000. A value < 1.5 was considered pathologic. CBCS without GHD served as the control group. Results: The study included 60 participants: 12 controls (mean age 14 ± 4.7 years) and 48 CBCS with GHD (mean age 16.6 ± 4.9 years), 8 of whom were not receiving rhGH therapy. The cohort showed a high prevalence of abnormal RHI values. Although there were no significant differences in weight or body mass index between groups, those with GHD, especially those not on rhGH therapy, had a higher prevalence of an RHI < 1.5, lower pathological adiponectin levels and a disrupted lipid profile. Conclusions: CBCS exhibited altered RHI values consistent with early endothelial biophysical dysfunction. Among patients with GHD, this impairment was further associated with an adverse lipid profile and signs of adipose tissue dysfunction. Recombinant growth hormone replacement therapy may contribute to a partial improvement in biochemical indicators of endothelial function.