Statin use improves the efficacy of nivolumab in patients with advanced renal cell carcinoma

Background Statins are widely used in an ageing population, including subjects with solid malignancies. However, no conclusive evidence is currently available on their potential influence on patients' outcome. We aimed to assess whether statin exposure affects the survival of patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. Patients and methods Medical records of patients with documented mRCC treated with second- or third-line nivolumab were reviewed at ten institutions from Italy, Spain and the USA. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall clinical benefit. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. Results A total of 219 patients with mRCC receiving nivolumab between January 2016 and September 2021 were eligible for inclusion in this study; 59 (27%) were statin users. The median OS (34.4 versus 18.6 months, p = 0.017) and PFS (11.7 versus 4.6 months, p = 0.013) resulted apparently longer in statin users. Stratified by age, longer median OS and PFS were associated with statin exposure in both patients aged ≥70 y (median OS: 21.4 versus 10.1 months, p = 0.047; median PFS: 16.4 versus 4.6 months, p = 0.022) and <70 y (median OS: 34.4 versus 21.4 months, p = 0.043; median PFS: 10.3 versus 4.6 months, p = 0.042). Overall clinical benefit resulted higher in statin users than non-users (71% versus 54%, p = 0.030). Conclusions Our study suggests a prognostic impact of statin use in patients receiving nivolumab for mRCC

Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes

Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes