Citations

SummaryObjectiveRising prevalence of obesity has led to increased rates of prediabetes and diabetes mellitus (DM) in children. This study compares rates of prediabetes and diabetes using two recommended screening tests (fasting plasma glucose [FPG] and haemoglobin A1c [HbA1c]).Study DesignData were collected prospectively from 37 multi‐component paediatric weight management programs in POWER (Paediatric Obesity Weight Evaluation Registry).ResultsFor this study, 3962 children with obesity without a known diagnosis of DM at presentation and for whom concurrent measurement of FPG and HbA1c were available were evaluated (median age 12.0 years [interquartile range, IQR 9.8, 14.6]; 48% males; median body mass index 95th percentile [%BMIp95] 134% [IQR 120, 151]). Notably, 10.7% had prediabetes based on FPG criteria (100–125 mg/dL), 18.6% had prediabetes based on HbA1c criteria (5.7%–6.4%), 0.9% had DM by FPG abnormality (≥126 mg/dL) and 1.1% had DM by HbA1c abnormality (≥6.5%). Discordance between the tests was observed for youth in both age groups (10–18 years [n = 2915] and age 2–9 years [n = 1047]).ConclusionThere is discordance between FPG and HbA1c for the diagnosis of prediabetes and DM in youth with obesity. Further studies are needed to understand the predictive capability of these tests for development of DM (in those diagnosed with prediabetes) and cardiometabolic risk.

Abstract The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age‐related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging‐induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose‐dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non‐human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age‐related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age‐related skeletal muscle phenotypes.

ABSTRACT Background Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Methods A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6–23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD −0.07 ml/min/1.73 m2 (95% CI −0.64–0.50)] or creatinine [SMD −0.08 mg/dl (95% CI −0.44–0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD −0.47 (95% CI −0.77 to −0.18)] and haemoglobin A1c levels [MD −0.85% (95% CI −1.41 to −0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD −0.43 ng/ml (95% CI −0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). Conclusions GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.

Abstract Background Hemiarthroplasty may be indicated for patients with distal radioulnar joint (DRUJ) arthritis. Recently, the use of the pyrocarbon metacarpophalangeal implant has been proposed as a novel means of treating DRUJ arthritis due to the materials improved mechanical properties and wear characteristics. Purpose This study compares midterm outcomes of metallic and pyrocarbon hemiarthroplasties for the treatment of symptomatic DRUJ arthritis. Questions of interest included outcomes and complications. Materials and Methods In total, 32 hemiarthroplasties, 10 metallic and 22 pyrocarbon, were performed between 2010 and 2020 by three surgeons at one tertiary medical center. Patients' retrospective outcomes were extracted from the electronic medical record. Results Postoperatively, the metallic implant group (mean follow-up: 38 months) demonstrated decreased pain but no changes in range of motion. Comparatively, the pyrocarbon group experienced an improved range of motion and postoperative pain (p < 0.05). Radiographic analysis demonstrated 10% of metallic implants and 9% of pyrocarbon implants to have resulted in thinning of the lateral cortex of the radius at the final follow-up. Minor complications in metallic and pyrocarbon implant groups warranting reoperation occurred at rates of 10 and 13.5% while implant failure occurred at a rate of 30 and 18%, respectively. Discussion Within this study, pyrocarbon implants resulted in significant functional improvement with comparable complication and failure rates to the metallic implant. Long-term stability demonstrated efficacy for both techniques in symptomatic DRUJ treatment. Type of Study/Level of Evidence Observational Case Series IV.

Abstract Background Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH. Objectives The objective of this study was to perform a meta‐analysis of published cases of nHLH. Methods A comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case. Results A total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0–11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6–27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% ( n = 28/147) of all neonates and 39% ( n = 15/38) of preterm neonates. Bicytopenia was absent in 26% ( n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases ( n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% ( n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time. Conclusions Evaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

ImportanceCancer is one of the leading causes of death in the United States, with the obesity epidemic contributing to its steady increase every year. Recent cohort studies find an association between bariatric surgery and reduced longitudinal cancer risk, but with heterogeneous findings.ObservationsThis review summarizes how obesity leads to an increased risk of developing cancer and synthesizes current evidence behind the potential for bariatric surgery to reduce longitudinal cancer risk. Overall, bariatric surgery appears to have the strongest and most consistent association with decreased incidence of developing breast, ovarian, and endometrial cancers. The association of bariatric surgery and the development of esophageal, gastric, liver, and pancreas cancer is heterogenous with studies showing either no association or decreased longitudinal incidences. Conversely, there have been preclinical and cohort studies implying an increased risk of developing colon and rectal cancer after bariatric surgery. A review and synthesis of the existing literature reveals epidemiologic shortcomings of cohort studies that potentially explain incongruencies observed between studies.Conclusions and RelevanceStudies examining the association of bariatric surgery and longitudinal cancer risk remain heterogeneous and could be explained by certain epidemiologic considerations. This review provides a framework to better define subgroups of patients at higher risk of developing cancer who would potentially benefit more from bariatric surgery, as well as subgroups where more caution should be exercised.