[Posted 8/Nov/2022]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Sinus tachycardia followed by atrial fibrillation and right bundle branch block are common ECG changes in patients with COVID-19 infection with raised IL-6. The possible association of cardiac injury in patients with COVID-19 infection with coexisting raised IL-6 levels should be explored further.

BACKGROUND: Cardiac injury is associated with high mortality in patients with COVID-19 infection. Electrocardiographic changes can give clues to the underlying cardiovascular abnormalities. Raised inflammatory markers like raised interleukin-6 (IL-6) are associated with arrhythmia, heart failure, and coronary artery disease. However, past studies have not highlighted the electrocardiographic abnormalities in patients with COVID-19 infection with raised IL- 6 levels. This study compared the electrocardiogram (ECG) changes in COVID-19 patients with high and normal IL-6 levels.

DETAILS: A retrospective analysis of ECG of 306 patients with COVID-19 infection was done, out of which 250 patients had normal IL- 6 levels, whereas 56 patients had raised IL-6 levels. IL-6 levels were measured in all the patients. Detailed clinicodemographic profile of all the serial COVID-19 patients admitted with moderate to severe COVID-19 pneumonia was noted from the hospital record section. Electrocardiographic findings and biochemical parameters of all the patients were noted. Out of 56 patients with raised IL-6 levels, 41 (73.2%) patients had ECG abnormalities compared to 177 (70.8%) patients with normal IL-6 levels. This difference was not statistically significant. However, ECG abnormality such as sinus tachycardia was significantly more common in patients with raised IL-6 levels than those with normal levels. Among patients with raised IL-6 levels who were discharged, 5 (16.6%) had sinus tachycardia, 2 (6.6%) had ST/T wave changes as compared to 15 (57.6%), and 10 (38.4%) who had tachycardia and ST/T wave change respectably succumbed to death. This difference was statistically significant.

Copyright © Journal of Family Medicine and Primary Care. All rights reserved.

Source: Kaeley, N., Mahala, P., Walia, R., et al. (2022). Electrocardiographic Abnormalities In Patients With Covid-19 Pneumonia And Raised Interleukin-6. J Family Med Prim Care. 2022; 11(10): 5902-5908. Published: October, 2022. DOI: 10.4103/jfmpc.jfmpc_135_22.

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

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

[Posted 25/Mar/2026]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: TLR8 GOF is an X-linked dominant disorder that should be considered in male and female patients with cytopenia, particularly severe neutropenia, lymphoproliferation with immune dysregulation, increased LGLs, and new to this cohort, red cell aplasia. Disease is refractory to medical management, and curative, allogeneic HCT should be considered early after diagnosis.

BACKGROUND: Toll-like receptor 8 (TLR8) gain-of-function (GOF) somatic variants were recently identified as causing severe neutropenia, lymphoproliferation, and immune dysregulation.

DETAILS: The expanded clinical and laboratory phenotype and management of 10 patients were reported, including the original cohort of 6 male patients. The first female patient was identified with TLR8 GOF who presented during infancy with pure red cell aplasia due to a germ line TLR8 variant, and 2 new disease-causing somatic variants in male patients. Eight patients had somatic mosaicism with peripheral blood variant allele fractions of 7% to 26%, and age of disease onset of 9 months to 28 years. All patients had neutropenia, most with severe neutropenia refractory to medical therapy. Anemia and thrombocytopenia were common. Bone marrow characteristically demonstrated severe myeloid hypoplasia and activated T-cell infiltrates and/or aggregates. An increased number of large granular lymphocytes (LGLs) was identified in 5 patients. Seven patients underwent allogeneic hematopoietic cell transplant (HCT). High rates of post-HCT cytopenia of unclear etiology and graft-versus-host disease were observed. Five patients are surviving at 1 to 3 years after HCT with full donor myeloid and T-cell chimerism, and resolution of disease phenotype. The 2 patients who presented during childhood and did not undergo HCT ultimately died from disease.

Copyright © The American Society of Hematology. All rights reserved.

Source: Arnold, D. E., Kaviany, S., Aluri, J., et al. Clinical Characteristics, Management, and Hematopoietic Cell Transplantation of Patients With TLR8 Gain-of-Function. Blood Adv. 2026; 10(6): 1967-1976. Published: March 24, 2026. DOI: 10.1182/bloodadvances.2025016338