Marsool, Mohammed Dheyaa

Sex and gender influence disease mechanisms and outcomes, yet their integration into medical curricula remains limited. Faculty knowledge and confidence are essential for effective incorporation. This study assessed baseline sex- and gender-specific health (SGSH) knowledge, attitudes, and comfort among medical school educators and delivered a multi-format faculty development intervention. A survey adapted from prior SGSH assessments was distributed to medical school block leaders before the intervention, measuring SGSH knowledge, comfort differentiating sex and gender, awareness of SGSH resources, and readiness to integrate SGSH content. The intervention included virtual and in-person grand rounds, distribution of How Sex and Gender Impact Clinical Practice , and a screening of Ms. Diagnosed . Of the 103 invited to participate, 68 educators (66% response rate) completed the baseline survey. Forty percent reported no prior SGSH training, and only 13.2% felt very comfortable with SGSH concepts. Although 94.1% correctly identified gender as a social construct and sex assignment at birth, 22% remained uncomfortable distinguishing the two. More than 80% were neutral or uncomfortable identifying SGSH resources. Comfort with curriculum integration varied: 45.6% felt comfortable, 32.4% neutral, and 22.1% uncomfortable, with differences observed across specialties. These findings reveal significant gaps in medical educators’ SGSH knowledge and comfort regardless of experience, with SGSH content narrowly confined to reproductive health topics. Simply providing resources is insufficient; educators need structured guidance on integration. By outlining baseline gaps and an intervention model, this study offers a framework for institutions seeking to enhance SGSH integration through interactive, longitudinal, multi-format faculty development approaches.

e20139 Background: Extensive-stage small cell lung cancer (ES-SCLC) frequently presents with brain metastases, affecting approximately 20% of the patients at diagnosis. The prognostic impact of baseline brain metastases on survival outcomes in patients treated with contemporary chemo-immunotherapy remains unclear, creating uncertainty in first-line treatment selection for this high-risk population. We conducted a systematic review and meta-analysis to evaluate the impact of baseline brain metastases on treatment outcomes in ES-SCLC. Methods: This PRISMA-compliant systematic review and meta-analysis was prospectively registered in PROSPERO. PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched from database inception through January 2026 to identify randomized controlled trials evaluating PD-1/PD-L1-based chemo-immunotherapy versus platinum-etoposide chemotherapy in adults with ES-SCLC. Two reviewers independently screened studies and extracted data, with discrepancies resolved by consensus. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled separately for patients with baseline brain metastases (BM+) and without brain metastases (BM−) using random-effects models with Hartung–Knapp adjustment. Analyses were performed using R. Prespecified subgroup analyses were conducted based on follow-up duration and immunotherapy regimen. Results: Twelve randomized controlled trials were included. Among patients with baseline brain metastases (BM+), pooled OS from seven studies did not show a significant survival benefit (HR 0.84, 95% CI 0.66–1.08, I² = 0.0%, P = 0.145), nor did pooled PFS from five studies (HR 1.03, 95% CI 0.60–1.79, I² = 0.0%). Subgroup analyses revealed no significant heterogeneity. In contrast, among patients without baseline brain metastases (BM−), pooled OS from nine studies demonstrated a significant survival benefit (HR 0.72, 95% CI 0.69–0.76, I² = 0.0%, P < 0.001), with corresponding improvement in PFS (HR 0.70, 95% CI 0.60–0.82, I² = 0.0%). These findings indicate a differential treatment effect according to baseline brain metastasis status. Conclusions: First-line chemo-immunotherapy does not apprear to confer a significant survival benefit in ES-SCLC patients with baseline brain metastases, reflecting a differential treatment effect by brain metastasis status. These findings suggest that baseline brain metastases should be considered in treatment selection and future clinical trial design and highlight the need for optimized systemic strategies for this high-risk population.

Background: Metabolic-associated fatty liver disease (MAFLD) affects approximately 30% of the global population and is associated with obesity and metabolic syndrome. Anthropometric indices such as body mass index (BMI), waist circumference (WC), and weight are crucial markers for evaluating the progression of MAFLD. Curcumin, a bioactive compound with anti-inflammatory and antioxidant properties, has been investigated for its potential to improve metabolic outcomes. This umbrella review aimed to systematically evaluate the effects of curcumin supplementation on anthropometric indices in patients with MAFLD, considering epidemiological strength and power analysis. Methods: An umbrella review of meta-analyses from randomized controlled trials was conducted. PubMed, Scopus, and Web of Science were searched up to September 2024. Meta-analyses assessing curcumin’s effects on BMI, weight, and WC in MAFLD patients were included. Quality was assessed using the A Measurement Tool to Assess Systematic Reviews version (AMSTAR-2) tool, and heterogeneity was evaluated using the I 2 statistic. Statistical analyses were performed using R and Stata 18 software. Results: Curcumin supplementation had no significant effect on BMI (standardized mean difference [SMD]: −0.01; 95% confidence interval [CI]: −0.24 to 0.21, P = .91) with low power (1-β = 0.03) and a low epidemiological grade according to GRADE criteria. Similarly, curcumin showed no significant effect on WC (SMD: −0.27; 95% CI: −0.57 to 0.04, P = .08) with high power (1-β = 0.96) but low epidemiological strength. However, curcumin significantly reduced weight (SMD: −0.12; 95% CI: −0.19 to −0.04, P < .01) with moderate power (1-β = 0.56) and moderate epidemiological strength. No significant effect of dose or effect of supplementation duration was found. Conclusion: Curcumin supplementation may result in a statistically detectable but clinically modest reduction in body weight in patients with MAFLD, while showing limited or no efficacy on BMI and waist circumference. The epidemiological strength of the evidence varies across outcomes and is of low to moderate quality. Further well-designed, high-quality randomized controlled trials are needed to confirm the clinical relevance of curcumin’s effects on anthropometric indices.

144 Background: Androgen receptor pathway inhibitors (abiraterone acetate [AAP], apalutamide [APA], enzalutamide [E], darolutamide [DARO] have become the cornerstone for pts with PCa due to survival benefits. Comparative data on fracture risk among ARPi are limited. This study quantified the risk of bone fractures with ARPi plus androgen deprivation therapy (ADT) and compared fracture risk across different ARPi agents. Methods: MEDLINE and EMBASE were searched from inception through September 1 st 2025 to identify positive phase III trials assessing ARPi in addition to ADT in pts with PCa (m0CRPC, mCSPC, mCRPC). Trials were included if they reported bone fractures in either arm. Pairwise, random-effects meta-analysis was conducted using Paul-Mendel approach. Sensitivity analyses using Hartung-Knapp (HK) adjustment was performed to assess robustness of results. To assess the comparative risk of bone fractures among different ARPi agents, mixed treatment comparisons were made using frequentist network meta-analysis. P-scores were computed to assess relative treatment rankings. Treatment effect was expressed as odds ratio (OR) with 95% confidence intervals (CI). Results: This systematic review included 13 phase III trials with 15468 pts (8890 received ARPi+ADT, 6578 received ADT alone). A total of 596 (6.7%) bone fractures were observed with ARPi+ADT compared to 180 (2.74%) with ADT alone. Patients receiving ARPi+ADT were associated with an increased risk of bone fractures compared to those receiving ADT (OR: 2.40; 95% CI: 1.93-2.98). Sensitivity analyses with HK adjustment showed consistent results (2.40; 1.88-3.06). There was no statistically significant effect modification by PCa clinical setting (p: 0.27). Mixed treatment comparisons showed a statistically significant increased risk of bone fractures with AAP+ADT (2.35; 1.29-4.27), APA+ADT (2.04; 1.47-2.86), and E+ADT (3.13; 2.44-4.00) but not with DARO+ADT (1.30; 0.80-2.08) when compared to ADT alone. Among different ARPi agents, E+ADT was associated with an increased risk compared to APA+ADT (1.54; 1.01-2.33) and DARO+ADT (2.44; 1.41-4.17). Ranking analysis showed that E+ADT was ranked as potentially the least safe treatment (P score: 0.05) in terms of relative fracture risk followed by AAP+ADT (P score: 0.30), APA+ADT (P score: 0.43), DARO+ADT (P score: 0.76). Sensitivity analyses limiting to mCSPC trials only showed consistent results. Conclusions: The risk of bone fractures varies among different ARPi agents, with enzalutamide posing the highest relative risk and darolutamide the lowest. These differences may guide treatment selection, particularly in pts with mCSPC and bone metastases. Prospective studies adjusting for covariates are needed to evaluate bone-protective strategies to mitigate fracture risk particularly in mCSPC patients who are considering treatment with ARPi.

483 Background: Sarcomatoid dedifferentiation (sRCC) in metastatic clear-cell renal cell carcinoma (mccRCC) confers aggressive disease and poor prognosis. We maintain a living meta-analysis of first-line immune checkpoint inhibitor (ICI)–based combinations in mccRCC (Riaz et al., Eur Urol Oncol 2021), which demonstrated improved survival with ICI-based regimens over sunitinib. Here, we present an updated synthesis focused on the comparative efficacy of ICI combinations in the sarcomatoid subset. Methods: A systematic search of MEDLINE, EMBASE, and CENTRAL through October 2025 was performed as part of our living meta-analysis of first-line mccRCC therapy. Eligible phase III RCTs compared ICI combinations (IO/IO or IO/TKI) versus sunitinib, including CheckMate 214, CheckMate 9ER, KEYNOTE-426, CLEAR/KEYNOTE-581, JAVELIN Renal 101, and IMmotion151. Extracted outcomes included overall (OS) and progression-free survival (PFS), and objective (ORR), complete (CR), and partial (PR) response rates. Random-effects meta-analyses generated pooled hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for response rates with 95% confidence intervals. Subgroup interaction analyses compared sarcomatoid versus non-sarcomatoid subgroups, with p < 0.1 considered significant. Results: Six phase III RCTs (n = 5,121; 624 sarcomatoid) were included. Across all ICI-based combinations, ICI therapy improved outcomes versus sunitinib in both sarcomatoid and non-sarcomatoid disease. In the pooled analysis, the OS interaction favored sRCC meeting the prespecified significance threshold for subgroup analyses (HR 0.53 vs 0.68; p-interaction = 0.06 < 0.10), while no significant interaction was seen for PFS. Response outcomes showed the strongest differential benefit, particularly with IO/TKI regimens. IO/IO results were directionally consistent but limited by smaller non-sarcomatoid samples. Conclusions: ICI-based combinations significantly improve survival and response outcomes versus sunitinib in mccRCC. Using a prespecified α = 0.10 for interaction testing, the pooled analysis showed a significant OS interaction and higher response rates in sRCC, indicating enhanced ICI sensitivity. These updated meta-analysis data support ICI regimens as the preferred first-line therapy for mRCC with sarcomatoid de-differentiation. Endpoint Regimen Subgroup (S = sarcomatoid; NS = non-sarcomatoid) Effect (95% CI) p-interaction PFS IO/IO S 0.51 (0.40–0.65) – IO/TKI S vs NS 0.48 (0.36–0.64) vs 0.46 (0.39–0.52) 0.81 OS IO/IO S 0.54 (0.07–4.42) – IO/TKI S vs NS 0.51 (0.17–1.48) vs 0.68 (0.30–1.58) 0.24 ORR IO/IO S 2.93 (0.49–17.37) – IO/TKI S vs NS 2.43 (1.84–3.21) vs 1.95 (1.67–2.28) 0.03 CR IO/IO S 3.81 (0.82–17.71) – IO/TKI S vs NS 5.93 (4.73–7.42) vs 2.85 (0.10–83.73) 0.007 PR IO/IO S 3.48 (1.70–7.11) – IO/TKI S vs NS 2.10 (1.78–2.47) vs 1.75 (1.18–2.61) <0.001

464 Background: Based on LITESPARK-005 trail, Belzutifan was FDA-approved to treat advanced RCC following ICI and a VEGF-TKI. We conducted a retrospective cohort study to report the real-world outcomes of Belzutifan in pre-treated RCC patients. Methods: A retrospective chart review of all patients who received Belzutifan at the Mayo Clinic Comprehensive Cancer Center between Dec 2023 and Sep 2025 was conducted. Patients treated for sporadic RCC were eligible; those with von Hippel–Lindau disease, non-RCC pathologies (e.g., Pheochromocytoma, ovarian cancer) were excluded. Radiologic response was assessed by trained curators using RECIST-defined criteria, approximated through systematic review of radiology reports with clinician adjudication when needed. Progression-free survival (PFS), defined as the time from treatment initiation to radiographic progression or death, was estimated using the Kaplan–Meier method. Non-progressors were censored at the last radiology assessment. Patients who discontinued therapy for non-progression reasons were censored at the last radiology assessment prior to discontinuation. Any-cause hypoxia and anemia were reported using CTCAEv5 definitions. Results: A total of 158 patients were identified; 83 (52.5%) who received Belzutifan for sporadic RCC were included. The remaining were excluded for VHL disease (68, 43%) or other pathologies (7, 4.4%). Median follow up was 12 months, 67% were male, median age was 70 (range 39, 94) with 57 patients (69%) were ≥ 65. 28 patients (34%) had a poor IMDC score at baseline. The cohort received a median of 3 previous lines of therapy (range 1,8). Median treatment duration was 3 months (IQR: 1-9.5). Median PFS was 5.7 months (95% CI, 3.8–8.7). At 12 and 18 months, 23.1% and 13.9% of patients, respectively, remained alive and progression-free. Corresponding OS rates at these time points were 60.2% and 51.5%. A confirmed ORR occurred in 12 patients (14.4%). Hypoxia occurred in 44 (53%) patients, median onset 31 days (range 1–270) and 29 (34.9%) required hospitalizations. Median hemoglobin (Hb) levels at baseline were 12.65 g/dl (range, 7.2-15.5), and 68 (82%) patients developed Hb decline on Belzutifan, 27 (32.5%) required transfusions. Conclusions: In an older, high-risk cohort with higher number of prior lines of therapy, Belzutifan yielded PFS/OS and ORR landmarks comparable to the trial supporting its effectiveness in the real world. Outcomes compared with LITESPARK-005 trial. Variable Real world cohort (Mayo Clinic) LITESPARK-005, Belzutifan arm Median PFS (months, 95% CI) 5.7 (3.8-8.7) 5.6 (3.9-7) 12-month PFS rate (%, 95% CI) 23.1% (14.4-33.4) 33.4% (28.4-33.5) 18-month PFS rate (%, 95% CI) 13.9% (7.7-23.9) 24% (19-29.4) 12-month OS rate (%, 95% CI) 60.2% (48.9-70.8) 67.9% (62.9-72.4) 18-month OS rate (%, 95% CI) 51.5% (40.6-62.9) 55.2% (50-60.1) ORR (%, 95% CI) 14.4% (7.7-23.9) 21.9% (17.8-26.5)