Results from the GCKD Study.

[Posted 20/May/2022]

AUDIENCE: Internal Medicine, Nephrology

KEY FINDINGS: The data support a link between elevated apoA-IV concentrations and reduced inflammation in moderate CKD. ApoA-IV appears to be an independent risk marker for reduced all-cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.

BACKGROUND: Chronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A-IV (apoA-IV) has antiatherogenic, antioxidative, anti-inflammatory and antithrombotic properties and levels increase significantly during the course of CKD. Study aimed to investigate the association between apoA-IV and all-cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study.

DETAILS: This was a prospective cohort study including 5141 Caucasian patients with available apoA-IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30-60 ml/min/1.73m² or an eGFR >60 ml/min/1.73m² in the presence of overt proteinuria. Median follow-up was 6.5 years. The association of apoA-IV with comorbidities at baseline and endpoints during follow-up was modelled adjusting for major confounders. Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA-IV quartile had the lowest high-sensitivity C-reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA-IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72-0.86, p = 0.0000003). During follow-up, each 10 mg/dl higher apoA-IV was significantly associated with a lower risk for all-cause mortality (600 cases, hazard ratio [HR] = 0.81, 95% CI 0.73-0.89, p = 0.00004), incident major adverse cardiovascular events (506 cases, HR = 0.88, 95% CI 0.79-0.99, p = 0.03) and death or hospitalizations due to heart failure (346 cases, HR = 0.84, 95% CI 0.73-0.96, p = 0.01).

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Schwaiger, J. P., Kollerits, B., Steinbrenner, I., et al. (2022). Apolipoprotein A-IV Concentrations And Clinical Outcomes In A Large Chronic Kidney Disease Cohort: Results from the GCKD Study. Journal of Internal Medicine. 2022; 291(5): 622-636. Published: May, 2022. DOI: 10.1111/joim.13437.

A Multinational Self-Controlled Case Series Study

[Posted 2/Apr/2026]

AUDIENCE: Internal Medicine, Neurology

KEY FINDINGS: In this multinational SCCS study, statin initiation may be associated with increased risk of new-onset MG during the first 6-12 months, with greater magnitude of risk elevation for higher intensity statin therapy. Consideration of the possibility of new-onset MG may be advisable within first 6-12 months after initiating statins, especially for medium-to-high-intensity statin therapy.

BACKGROUND: Evidence regarding the risk of new-onset myasthenia gravis (MG) following statin therapy initiation is limited. Purpose of this study is to investigate this potential adverse effect using multinational real-world population-based data.

DETAILS: A self-controlled case series (SCCS) study was conducted using electronic medical records and claims databases from Hong Kong, the United Kingdom (UK) and Japan. Individuals aged >=18 years with first diagnosis of MG and initiated statins were included. Conditional Poisson regression compared the risk of MG in different risk periods (up to 2 years after initiation) with non-exposure period, adjusted for age. Pooled results based on meta-analysis across all study sites were reported. In total, 2267 MG cases were analysed. Combined across all study sites, a significantly increased risk of incident MG was observed during the first year after statin initiation compared to non-exposure period, with a higher risk from Days 0-179 (pooled incidence rate ratio [IRR] [95% CI]: 2.662 [1.276-5.553]) than Days 180-364 (1.407 [1.014-1.954]). No increased risk of MG was observed more than 1 year after statin initiation (1.011 [0.848-1.206]). Moreover, the magnitude of MG risk elevation within the first 180 days after statin initiation was more pronounced with higher intensity statin regimens.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Ka Chun Yan, V., Xu, W., Taniguchi, Y., et al. Myasthenia Gravis Following the Initiation of Statin Therapy: A Multinational Self-Controlled Case Series Study. Journal of Internal Medicine. 2026; 299(4):502-514. Published: April, 2026. DOI: 10.1111/joim.70072Digital Object Identifier (DOI)

A Multicenter Cohort Study

[Posted 1/Apr/2026]

AUDIENCE: Endocrinology, Internal Medicine

KEY FINDINGS: A 30-unit increase in GGT over time was associated with a substantially higher risk of developing type 2 diabetes in children with MASLD. Together with AST, GGT may provide clinicians with concrete, routinely available parameters to monitor for early risk stratification. Further validation in independent cohorts is needed to confirm these findings and inform clinical application.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children and is linked to type 2 diabetes. This study evaluates whether longitudinal changes in liver chemistries - γ-glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) - can serve as biomarkers of increased type 2 diabetes risk in children with MASLD.

DETAILS: This multicenter longitudinal cohort study followed 1,035 children with biopsy-confirmed MASLD, without type 2 diabetes at baseline, for a mean of 3.9 years. Liver chemistries were measured annually, and type 2 diabetes was diagnosed based on fasting glucose, HbA1c, and clinical diagnosis. Extended Cox models with inverse probability weighting were used to evaluate associations between liver enzyme trajectories and type 2 diabetes risk. The cumulative incidence of type 2 diabetes was 12.3%. Increases in GGT (hazard ratio [HR] 1.55; 95% CI 1.34-1.80), AST (HR 1.31; 95% CI 1.20-1.43), and ALT (HR 1.13; 95% CI 1.07-1.20) were associated with a higher risk of developing type 2 diabetes in the independent models. In the mutual model with all three liver chemistries, only GGT and AST remained significant.

Copyright © American Diabetes Association. All rights reserved.

Source: Thai, N. Q. N., Chun, L. F., Newton, K. P., et al. Longitudinal Analysis of Liver Chemistry Trajectories and Risk of Type 2 Diabetes in Children With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Multicenter Cohort Study. Diabetes Care . 2026; 598-606. 49(4): Published: April, 2026. DOI: 10.2337/dc25-1532

Systematic Review and Meta-Analysis

[Posted 31/Mar/2026]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: Effect estimates of TSP-9 performance demonstrate that the test provides risk stratification for BE patients. The TSP-9 test can provide clinically impactful results to enable escalation of care for high-risk patients or to identify low-risk patients who can be safely managed with routine surveillance.

BACKGROUND: A systematic review and meta-analysis of published clinical validity studies was conducted to evaluate the predictive performance of the TSP-9 test. Identifying patients with Barrett’s esophagus (BE) who will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is challenging. The tissue systems pathology (TSP-9) test can predict risk of progression to HGD/EAC in BE patients.

DETAILS: Databases were searched for studies that assessed the clinical validity of TSP-9, and data describing progressors, non-progressors, TSP-9 results, and hazard ratios (HR) with 95% confidence intervals (CIs) were extracted. Odds ratios (OR), sensitivity, specificity, and prevalence-adjusted positive and negative predictive values (PPV_adj/NPV_adj) were calculated and used for meta-analysis. Six studies met eligibility criteria, comprising 699 patients. ORs and HRs for TSP-9 had mean common effect size estimates of 6.52 (95% CI: 4.40-9.66, P<0.0001, I²=33%) and 6.66 (95% CI: 4.59-9.66, P<0.0001, I²=0%), respectively, for predicting progression to HGD/EAC. Mean common effect size estimates were 61% (95% CI: 54%-68%) for sensitivity, 81% (95% CI: 78%-84%) for specificity, 28% (95% CI: 17%-42%) for PPV_adj (high risk), 14% (95% CI: 9%-21%) for PPV_adj (high/int risk), and 97% (95% CI: 96%-98%) for NPV_adj with minimal inter-study heterogeneity (I2=79%, 21%, 0%, 0%, and 0%, respectively).

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Houghton, C. C., Ditah, I., Leggett, C. L., et al. The Tissue Systems Pathology Test Predicts Risk of Progression in Patients With Barrett's Esophagus: Systematic Review and Meta-Analysis. Journal of Clinical Gastroenterology. 2026; 60(4)): 299-308. Published: April, 2026. DOI: 10.1097/MCG.0000000000002255

[Posted 30/Mar/2026]

AUDIENCE: Cardiology, Oncology, Emergency Medicine

KEY FINDINGS: Hs-TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs-TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

BACKGROUND: Immune-checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI-related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI-treated patients are limited.

DETAILS: All patients treated with ICI who had hs-TnT (high-sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs-TnT elevation were assessed. Risks of cardiac events were compared across hs-TnT elevation causes. Of 5423 patients treated with ICI, 1669 had post-ICI hs-TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1-year follow-up. Hs-TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7-238.0], P<0.001), followed by hs-TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs-TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4-15.3], P<0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events.

Copyright © American Heart Association, Inc. All rights reserved.

Source: Pietri, M. P., Farina, J. M., Awad, K., et al. Diagnostic and Prognostic Value of High-Sensitivity Troponin T for Cardiovascular Outcomes in Patients Receiving Immune Checkpoint Inhibitor Therapy. American Heart Association. 2026; 15(6). Published: March 17, 2026. DOI: 10.1161/JAHA.125.04168

Mortality and 5.5-Year Neurodevelopmental Outcomes of a Randomized Clinical Trial

[Posted 26/Mar/2026]

AUDIENCE: Pediatrics

KEY FINDINGS: Treatment with HC started between 7 and 14 days after birth in infants born preterm at risk of BPD did not affect death or moderate-severe NDI nor any of the separate developmental outcome measures at 5.5 years of corrected age.

BACKGROUND: Purpose of this study is to examine neurodevelopmental outcomes at 5.5 years of corrected age in children included in the Systemic hydrocortisone (HC) To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) study, and to investigate the neurodevelopmental outcomes and mortality with HC treatment started between 7 and 14 days after birth compared with placebo in infants born preterm who required mechanical ventilation. NDI was assessed in 213 of the 277 (77%) surviving children. Children attending follow-up were more likely to have highly educated or nonsmoking parents and had better neurodevelopmental outcomes at 2 years of corrected age than nonattending children. Baseline characteristics of assessed children were comparable between treatment arms. No significant difference was found on the primary outcome (OR 0.75; 95% CI 0.49-1.14; P = .18). All developmental outcomes were comparable between the HC and placebo group.

DETAILS: Data at 5.5 years of corrected age on cognitive, motor and neurosensory functioning, behavior, schooling, and general health outcomes were derived from regular follow-up visits. The primary outcome was death or moderate-severe neurodevelopmental impairment (NDI, complete case analysis), with NDI defined as a disability in at least 1 of the domains of cognition, motor development, vision, or hearing. Other outcomes included neurologic and behavioral assessments as well as parent reports of service use and school function.

Copyright © Elsevier Inc. All rights reserved.

Source: de Baat, T., van de Loo, M., Aarnoudse-Moens, C. S. H., et al. Effect of Systemic Hydrocortisone in Ventilated Infants Born Preterm: Mortality and 5.5-Year Neurodevelopmental Outcomes of a Randomized Clinical Trial. The Journal of Pediatrics. 2026; Published: March, 2026. DOI: 10.1016/j.jpeds.2025.114954