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Abstract We conducted this systematic review and meta-analysis to clarify the trend of precocious puberty (PP) incidence after the COVID-19 outbreak and explore potential contributing factors, such as age at presentation and body mass index (BMI) SD score (SDS). Children visiting pediatric endocrinology clinics for the first time for suspected PP were included. We searched databases until February 28, 2023, for studies reporting various indicators of PP incidence before and during the pandemic. Total numbers of events and observations were recorded. A meta-analysis was performed to compare the odds of PP, BMI SDS, and age at presentation between the 2 periods. The dose-response relationships between time points (by number of years away from the pandemic) and PP risk were explored. In summary, a total of 32 studies including 24 200 participants were recruited. The COVID-19 pandemic was associated with the increasing odds of PP among children referred for a suspicious condition (odds ratio = 1.96; 95% CI, 1.56-2.47; I2 = 54%; P < .001). Sensitivity analysis confirmed the robustness of the findings. The BMI SDS did not vary between the 2 periods, whereas age at presentation was lower after the pandemic. Precocious puberty incidence increased more rapidly during the pandemic period than during the prepandemic period. Trial registration: International Prospective Register of Systematic Reviews (PROSPERO; identifier: CRD42023402212)

ImportanceImmune checkpoint inhibitors (ICIs) improve outcomes in a wide range of cancers; however, serious adverse effects, including cardiovascular adverse effects (CVAEs), can occur.ObjectiveTo determine the incidence of CVAEs and analyze data on the management of myocarditis in patients exposed to ICIs.Data SourcesPubMed, Embase, and Cochrane Central Register of Controlled Trials from inception were searched on April 4, 2023.Study SelectionTwo separate studies were performed. Key inclusion criteria for study 1 were phases 1 to 4 trials involving adults with malignant neoplasms treated with an ICI and toxicity data; for study 2, publications (case reports and retrospective analyses) on clinical manifestations and treatment of patients with ICI-induced CVAEs. Studies with dose escalation or fewer than 11 patients in each group and all case reports, retrospective analyses, letters, reviews, and editorials were excluded from study 1. Studies not published in English were excluded from study 2.Data Extraction and SynthesisThe PRISMA guidelines and Cochrane Handbook for Systematic Reviews were followed. Data were extracted independently by 2 researchers. A meta-analysis of the incidence of CVAEs in clinical trials and a systematic review of the evidence for the management of myocarditis were performed. Data were pooled using a random-effects model.Main Outcomes and MeasuresIn study 1, the primary outcome was incidence CVAEs in clinical trials with ICIs and ICI combination therapies. Study 2 examined evidence supporting specific management strategies that may decrease the mortality rate of myocarditis. The primary outcomes were planned before data collection began.ResultsIn study 1, a total of 83 315 unique participants in 589 unique trials were included in the meta-analysis. Incidence of CVAEs induced by anti–programmed cell death 1 and/or programmed cell death ligand 1 was 0.80% (95% CI, 0%-1.66%) in clinical trials, with no differences between the compounds, except for cemiplimab, which was associated with a higher risk of CVAEs. Incidence of CVAEs following ipilimumab treatment was 1.07% (95% CI, 0%-2.58%). The incidence of myocarditis was significantly higher following treatment with dual ICIs. However, CVAE incidence was not higher with dual ICIs, ICI combination with chemotherapy, or tyrosine kinase inhibitors. Evidence from randomized clinical trials on recommended monitoring and treatment strategies for ICI-induced myocarditis was lacking. Study 2 showed that myocarditis-associated mortality occurred in 83 of 220 patients (37.7%). Prospective data from 40 patients with myocarditis indicated that systematic screening for respiratory muscle involvement, coupled with active ventilation, prompt use of abatacept, and the addition of ruxolitinib, may decrease the mortality rate.Conclusions and RelevanceImmune checkpoint inhibitor–induced CVAEs and/or myocarditis were recorded in 1.07% of patients in clinical trials. The CVAE mortality risk remains high, justifying the need for monitoring and management strategies for which evidence from randomized clinical trials is absent. Early recognition, ICI therapy cessation, prompt initiation of corticosteroid therapy, and escalation of therapy are all crucial elements for achieving optimal outcomes. Prospective clinical trials or at least prospective registration of treatments and outcomes are highly warranted.

INTRODUCTION: Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression. METHODS: Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression. RESULTS: A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11–3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04–3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes. DISCUSSION: Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

Purpose To assess the relation between tendon migration, as measured by radiostereometric analysis, and patient‐reported outcome measures (PROMs) after biceps tenodesis (BT); to determine the likelihood of achieving clinically significant outcomes (CSOs) after BT; and to identify factors that impact CSO achievement. Methods Patients undergoing arthroscopic suprapectoral or open subpectoral BT at a single, high‐volume academic medical center were prospectively enrolled. A tantalum bead sutured to the tenodesis construct was used as a radiopaque marker. Biceps tendon migration was measured on calibrated radiographs at 12 weeks postoperatively. PROMs (Constant‐Murley, Single Assessment Numeric Evaluation [SANE], and Patient‐Reported Outcomes Measurement Information System–Upper Extremity [PROMIS‐UE] scores) were collected preoperatively and at minimum 2‐year follow‐up. Results Of 115 patients enrolled, 94 (82%) were included (median age, 52 years; median body mass index, 31.4). At a mean follow‐up of 2.9 years, the median Constant‐Murley, SANE, and PROMIS‐UE scores were 33 (interquartile range [IQR], 26‐35), 90 (IQR, 80‐99), and 47 (IQR, 42‐58), respectively. Median tantalum bead migration was 6.5 mm (IQR, 1.8‐13.8 mm). There were significant correlations between migration and Constant‐Murley score ( r 2 = 0.222; β = –0.554 [95% confidence interval (CI), –1.027 to –0.081]; P = .022), SANE score ( r 2 = 0.238; β = –0.198 [95% CI, –0.337 to –0.058]; P = .006), and PROMIS‐UE score ( r 2 = 0.233; β = –0.406 [95% CI, –0.707 to –0.104]; P = .009). On univariable analysis, higher body mass index was associated with achievement of substantial clinical benefit (unadjusted odds ratio [OR], 1.078 [95% CI, 1.007 to 1.161]; P = .038). Greater bead migration was negatively associated with achievement of the minimal clinically important difference (unadjusted OR, 0.969 [95% CI, 0.943 to 0.993]; P = .014) and patient acceptable symptomatic state (unadjusted OR, 0.965 [95% CI, 0.937 to 0.989]; P = .008) on all 3 instruments. Conclusions A 1‐cm increase in post‐tenodesis biceps tendon migration was associated with a decrease in the Constant‐Murley, SANE, and PROMIS‐UE scores of 6, 2, and 4 points, respectively, at a mean of 2.9 years after surgery. Most patients achieved CSOs for these PROMs by latest follow‐up, and greater biceps tendon construct migration was negatively associated with the likelihood of CSO achievement. Level of Evidence Level IV, retrospective case series.