Introduction: The increasing utilization of real-world data platforms in medical research necessitates a comprehensive understanding of their methodological strengths and limitations. TriNetX has emerged as a significant platform for exploring large healthcare datasets. This review aims to critically evaluate the methodological framework and limitations of TriNetX, assess the impact of electronic health record coding accuracy on data reliability, and analyze the platform's capacity for generating generalizable real-world evidence in clinical research. Methods: We conducted a comprehensive review examining TriNetX's data architecture, quality metrics, and research applications, focusing on data integrity, platform architecture, and the external validity of research findings. Results: The analysis reveals significant methodological considerations. TriNetX's reliance on retrospective data introduces biases such as selection bias and confounding variables. The coding accuracy of electronic health records, which have not been independently validated, is a critical determinant of data reliability. The demographic representation is limited, affecting the generalizability of results. Discussion: Despite its extensive use, TriNetX's effective utilization requires careful consideration of its inherent limitations. The platform's data, predominantly from insured populations in academic and acute care settings, may not fully represent broader demographic groups. Addressing these methodological constraints is crucial for enhancing the reliability and applicability of research findings derived from TriNetX. Conclusions: TriNetX is a valuable resource for healthcare research. However, its limitations must be acknowledged, and future research should focus on standardizing data collection and enhancing data validation processes to mitigate platform-specific biases and improve the quality and applicability of the findings.

The term steatotic liver disease (SLD) is now used to describe conditions involving fat accumulation in the liver. SLD term includes a spectrum of defined and less defined disorders: metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and metabolic and ALD (Met-ALD), where both cardiometabolic risk factors, such as obesity, diabetes, or dyslipidemia, and alcohol consumption function in disease development and progression. Met-ALD is defined as liver disease in men with at least 1 cardiometabolic risk factor who also consume 210–420 g of alcohol per week (approximately 30–60 g per day), whereas for women, it is defined as at least 1 cardiometabolic risk factor in addition to consumption of 140–350 g of alcohol per week (approximately 20–50 g per day). This level of alcohol intake exceeds the thresholds traditionally used to exclude alcohol as a contributing factor in MASLD, but it remains below the levels typically associated with classic ALD. Met-ALD is estimated to affect about 17 million people in the United States It is a unique disease with the risk of cirrhosis, hepatocellular carcinoma, and mortality different from those with MASLD or ALD. Its treatment relies mainly on weight loss, alcohol abstinence, and control of cardiometabolic risk factors. Novel medications such as glucagon-like peptide-1 agonists and fibroblast growth factor s21 analogs may be promising future therapies for the treatment of Met-ALD.

Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in diagnosing polycythemia. We conducted a systematic literature review of the Medline data through Pubmed and Google Scholar. We included the articles which described confirmed PV associated with elevated EPO level. Our search strategy included the following terms in Pubmed (((polycythemia vera[MeSH Terms]) OR (jak2 protein tyrosine kinase[MeSH Terms])) OR (Myeloproliferative Disorders[MeSH Terms])) AND (Erythropoietin[MeSH Terms]), and 'polycythemia vera with erythropoietin' in Google Scholar. Our research yielded four cases of PV with elevated EPO levels. The most common symptom was a headache. Thrombotic phenomena happened in a single case in the form of Budd-Chiari syndrome. The mean Hb level was 20.2 gm/dl, and the EPO level was 213 mlU/mL. Although PV is usually associated with low EPO levels, high levels do not exclude this diagnosis. Workup should include testing for JAK2 mutation and bone marrow biopsy in the presence of suggestive signs and symptoms. Novel biomarkers are also being proposed to aid in the diagnosis. Although elevated EPO levels suggest secondary causes of polycythemia, cases where elevated EPO levels were associated with an underlying PV are reported in the literature, and we have summarized a review of them. Workup for polycythemia should include JAK2 mutation testing if signs and symptoms suggest PV even if EPO is elevated.

Chronic myeloid leukemia (CML) is one of the myeloproliferative neoplasms whose incidence peaks in older individuals and is characterized by the uncontrolled proliferation of cells in the myeloid cell line. It can present with symptoms related to leukocytosis or splenomegaly, and it can also be asymptomatic and found incidentally. Nilotinib is a second-generation tyrosine kinase inhibitor used in the treatment of the chronic phase of CML and was found to cause diabetes mellitus among other adverse effects. These adverse effects seem to occur after a few months to a few years of drug administration. Type-two diabetes is the most common type of diabetes; its hallmark being insulin resistance with resultant hyperglycemia. Most often, it has no symptoms and is usually found as an incidental finding or on screening. Here we present a 45-year old Chinese female, who was diagnosed with CML chronic phase after an incidental finding of leukocytosis; treated with nilotinib as upfront for CML, and developed diabetes mellitus after about one and a half years of treatment, which was treated with metformin.

INTRODUCTION: Esophageal dilation procedures are frequently performed on patients who are taking antithrombotic medications. The aim of this study was to evaluate whether patients on antithrombotic therapies have an increased risk of bleeding from esophageal dilation. METHODS: A retrospective propensity-matched cohort study was conducted to evaluate patients in the TriNetX US Collaborative Network database who underwent esophageal dilation procedures. The primary outcome was to assess the effect of anticoagulants and dual-antiplatelet therapies (DAPTs) on the rate of postprocedural gastrointestinal bleeding within 30 days. RESULTS: Patients on anticoagulants were found to be at higher risk of postprocedural gastrointestinal bleeding compared with patients not on anticoagulants (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06–1.92; P = 0.017). The anticoagulant group had higher rates of blood transfusion and intensive care unit admission. The DAPT group had a higher rate of gastrointestinal bleeding compared with no antiplatelet therapy, though this did not reach statistical significance (RR, 1.64; 95% CI, 0.97–2.75; P = 0.06). When compared with aspirin monotherapy, the difference in bleeding rates was also not statistically significant (RR, 1.36; 95% CI, 0.84–2.19; P = 0.2). There was no difference in the rates of blood transfusion or intensive care unit admission when DAPT was compared separately with aspirin and with no antiplatelet groups. In addition, early resumption of anticoagulation or antiplatelet therapy was not associated with increased postprocedural bleeding. DISCUSSION: Patients on anticoagulants at the time of esophageal dilation were at higher risk of postprocedural bleeding. DAPT was numerically associated with a higher risk of bleeding, but this did not reach statistical significance. These findings aim to inform the clinical decision making in preprocedure and postprocedure management of esophageal dilation procedures.