IntroductionTo verify our hypothesis that psoriatic arthritis (PsA) is mainly genetically predetermined and distinct from psoriasis (PsO), we use the TriNetX database to investigate whether intrinsic factors outweigh externals in PsA emergence in PsO patients.MethodsWe conducted three retrospective cohort studies utilizing information from the TriNetX network, whether (a) PsO patients with type 2 diabetes mellitus (DM) face an elevated risk of developing PsA compared to those without type 2 DM; (b) PsO patients who smoke face a higher risk of PsA; and (c) PsO patients with type 2 DM who smoke are more likely to develop PsA than those who do not smoke.ResultsPsO patients with type 2 DM exhibited an elevated risk of developing PsA [hazard ratio (HR), 1.11; 95% CI 1.03–1.20], with the combined outcome demonstrating a heightened HR of 1.31 (95% CI 1.25–1.37). PsO patients with a smoking history exhibited an elevated risk of developing PsA (HR, 1.11; 95% CI 1.06–1.17), with the combined outcome demonstrating a heightened HR of 1.28 (95% CI 1.24–1.33). PsO patients with type 2 DM and a history of smoking were not found to be associated with an increased risk of developing PsA (HR, 1.05; 95% CI 0.92–1.20). However, the combined result revealed a higher risk of 1.15 (95% CI 1.06).DiscussionThese findings suggested that intrinsic factors outweigh external factors in PsA emergence in PsO patients. Further studies may focus on genetic disparities between PsO and PsA as potential risk indicators rather than solely on phenotypic distinctions.

A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, a federated database comprising de-identified electronic health records from 142 healthcare organizations (HCOs). The database was queried on March 13, 2025, to identify patients diagnosed with gastroesophageal reflux disease (GERD). Patients were stratified into two cohorts based on proton pump inhibitor (PPI) exposure. The GERD+PPI cohort included patients with a diagnosis of GERD (ICD-10: K21) who had ≥2 prescriptions for a PPI (omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, or rabeprazole) within 5 years prior to the index date. The GERD control cohort included GERD patients with no history of PPI use, defined as no recorded prescriptions for any listed PPIs at any time. Patients were excluded in the risk analysis if they had a history of cutaneous fungal infections, including onychomycosis, tinea corporis, tinea pedis, tinea cruris, or cutaneous candidiasis. Additional exclusions included a history of systemic antifungal use (fluconazole, terbinafine, itraconazole) within 1 day prior to the index date or a history of immunodeficiency conditions, including HIV (ICD-10: B20), solid organ transplantation, or primary immunodeficiency disorders (ICD-10: D80-D84). Cohorts were propensity score-matched (1:1) to minimize confounding, using variables including age, sex, race/ethnicity, diabetes, obesity, immunosuppression, and concurrent medication use. Standardized mean differences (SMDs) were used to assess balance between matched cohorts. The primary outcome was the incidence of cutaneous fungal infections following PPI use. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated using logistic regression. A p-value <0.05 was considered statistically significant. All statistical analyses were conducted within the TriNetX platform.

BackgroundPhenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcusaureusinfections (SAIs) has been done leaving potential novel risk factors or complications undiscovered.Method and cohortsWe tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively.ResultsForty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria.ConclusionsThe PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation.

ObjectivesThe treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting.Materials and methodsWe enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod.ResultsTotally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort.ConclusionThere was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.

IntroductionWe conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.MethodsThe study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.ResultsUse of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.DiscussionSelective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.