Emory Clinic

ABSTRACTBackgroundPost‐embolization syndrome after transarterial chemoembolization (TACE) and Yttrium‐90 radioembolization (TARE) causes significant morbidity. Understanding whether discharge prescriptions influence short‐term outcomes may guide standardized pain‐management strategies.MethodsA retrospective cohort study of 3191 patients (3988 procedures) with hepatocellular carcinoma from the Merative MarketScan Databases (2009–2022) was performed. The composite outcome was 7‐day drug escalation or hospital readmission. Bivariate logistic regression identified candidate variables (p < 0.10); multivariable logistic regression with patient‐clustered robust standard errors estimated adjusted odds ratios (aORs), adjusting for age, sex, and Charlson Comorbidity Index (CCI).ResultsCompared to patients discharged without opioids post‐chemoembolization, those prescribed opioids at discharge had 83% lower odds of experiencing drug escalation or readmission (odds ratio [aOR] = 0.17, p < 0.001), and those undergoing radioembolization had 59% lower odds (aOR = 0.41, p < 0.001). Being prescribed antiemetics or steroids was also associated with lower odds of escalation/readmission events, with percentages varying by procedure type.ConclusionsPrescribing opioids, along with antiemetics and steroids, at discharge may reduce the likelihood of post‐procedural events, such as drug escalation and readmission, in patients undergoing trans‐arterial chemoembolization and radioembolization for hepatocellular carcinoma. These findings highlight the importance of a comprehensive pain management strategy in interventional oncology and warrant consideration in clinical practice guidelines.

Objectives:Epigenetic clocks are biomarkers of aging. Epigenetic clocks are associated with early-life famine exposure. We investigated the impact of a cluster-randomized early-life nutrition intervention on epigenetic age.Methods:We analyzed follow-up data from participants in the INCAP Nutrition Supplementation Trial, conducted in 4 villages in eastern Guatemala. DNA methylation was measured in buffy coat samples using the Illumina Infinium™ MethylationEPICv2.0 array and standard quality control procedures.Epigenetic age was quantified using DunedinPACE, PhenoAge, and GrimAge. PhenoAge and GrimAge acceleration were calculated as residuals by regressing epigenetic age on chronological age. We used intent-to-treat difference-in-difference modeling to assess the impact of a protein-energy supplement provided during the first 1,000 days of life (conception to age 2y) on epigenetic age in middle adulthood. Covariates included sex, birth year, the trial supplement type (atole [intervention] vs. fresco [control]), exposure period of supplement (any of the first 1,000 days, other), and a random effect to account for sibships. The primary coefficient of interest was represented by the interaction between supplement type and exposure period.Results:The analysis included 1095 participants (mean age 45.0 y (SD 4.3); 60.3 % female, 40.3 % exposed to any atole during the first 1,000 days, mean DunedinPACE 1.2 (SD 0.1), Phenoage 46.7 y (SD 6.7), and GrimAge 56.3 y (SD 4.1). In difference-in-difference analyses, exposure to atole during any of the first 1,000-day period was associated with lower DunedinPACE (−0.03, 95% CI −0.06, −0.004), PhenoAge acceleration (− 1.91 y, 95% CI −3.43, −0.39), and GrimAge acceleration (−0.85 y, 95% CI −1.53, −0.11) compared to other exposures. Following additional adjustment for cell type proportions, the direction of the coefficients remained the same but were no longer statistically significant.Conclusions:Exposure to atole during the first 1,000 days was associated with modest reductions in epigenetic age as measured by DunedinPACE, PhenoAge, and GrimAge. These findings complement prior evidence of epigenetic age acceleration among individuals with early-life famine exposure.

Stress hyperglycemia (SH) during acute illness is linked to adverse surgical outcomes, yet the accompanying metabolic perturbations are incompletely characterized. We profiled longitudinal metabolic changes in adults without diabetes undergoing cardiac surgery to identify pathways associated with perioperative SH (defined as point of care glucose ≥140 mg/dL on ≥3 readings or ≥180 mg/dL once). Blood was collected at baseline before surgery (T0) and at 2 h (T1), 24–48 h (T2), and 72–96 h (T3) after surgical initiation. High resolution metabolomics (LC–MS) was integrated with continuous glucose monitoring and inflammatory/cardiac biomarkers. At T0, several pathways were associated with subsequent SH, including bile acid metabolism, the carnitine shuttle, and fatty acid oxidation, suggesting preoperative metabolic susceptibility. In longitudinal analyses, participants who developed SH showed coordinated postoperative changes with significant enrichment of pathways not evident at baseline, C21 steroid hormone biosynthesis, glycerophospholipid metabolism, and glycosphingolipid (ceramide) metabolism, consistent with lipid remodeling and inflammatory signaling during surgical stress. Individuals with SH also exhibited higher inflammatory biomarker levels (high sensitivity C reactive protein and soluble urokinase plasminogen activator receptor). A machine learning model using early metabolomic features predicted SH with an area under the receiver operating characteristic curve of 0.86. These findings highlight distinct preoperative and perioperative metabolic trajectories associated with SH and implicate established dysglycemia-related pathways, as well as stress-induced pathways in perioperative metabolic dysregulation. Pathway enrichment analyses were exploratory and hypothesis-generating; validation in larger cohorts and assessment of implications for clinical outcomes are warranted.

Obesity is a multifactorial disease with increasing prevalence in the United States and a major contributor to cardiovascular disease. The Lancet Commission recently issued a new definition of obesity to better capture individuals with excess body fat and metabolic consequences of adiposity. In this article, we provide a practical implementation of this new definition into a clinical practice using the ABC model of cardiovascular prevention, a framework to characterize major atherosclerotic risk factors. We recommend to emphasize B is for body fat, with routine measurement using body mass index and waist circumference, tailored history and physical exam to identify obesity-related diseases, lifestyle guidance, and pharmacological recommendations.

Significant lipid metabolism changes during pregnancy are essential for fetal development. However, when complicated by pre-existing cardiometabolic risk factors like obesity, hypertension, and diabetes, there is an increased risk for adverse maternal and fetal outcomes and future cardiovascular events. Despite the rising prevalence of maternal obesity and other co-morbidities, there continues to be a lack of clear guidelines for screening and treating dyslipidaemia during pregnancy. This review aims to highlight the physiological changes in lipid metabolism during pregnancy, explore the association between dyslipidaemia and adverse outcomes, summarize current treatment options, and identify research gaps pertaining to management of perinatal dyslipidaemia. Enhancing our understanding of dyslipidaemia in pregnancy is crucial for improving maternal and fetal health outcomes, guiding future offspring risk assessment, and informing therapy guidelines.