Citations

Abstract Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( CLPTM1L , rs383009:T>C, T Allele Frequency=0.51, OR:1.45, P value=1.24×10 -8 ), a locus previously associated with PDAC. Known loci at 5p15.33, 7q32.3, 8q24.21 and 7q25.1 also replicated (P value <0.01). Multi-ancestral fine-mapping identified two potential causal SNPs (rs3830069 and rs2735940) at 5p15.33. Collectively these findings identified novel PDAC risk loci and expanded our understanding of this deadly cancer in underrepresented populations, emphasizing the multifactorial nature of PDAC risk including inherited genetic and non-genetic factors. Statement of Significance To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.

We previously reported initial results of the pivotal phase II trial of atezolizumab for patients with alveolar soft part sarcoma (ASPS; ClinicalTrials.gov identifier: NCT03141684 ). Here, we report on three additional years of observation. Fifty-three patients with ASPS received atezolizumab. Median duration of response increased to 37.0 months. Objective response rate (ORR) and median progression-free survival (mPFS) remained essentially as previously reported (35.8% [95% CI, 23.1 to 50.2] and 20.8 months [IQR, 7.6-not reached], respectively). ASPSCR1::TFE3 fusion type was determined for 47/53 patients; ORR and mPFS were higher among the 41 patients expressing type 1 (43.9% [95% CI, 28.5 to 60.2] and 28.3 months [IQR, 9.2-not reached], respectively) than the six patients expressing type 2 (0% [95% CI, 0 to 45.9] and 7.5 months [IQR, 3.9-not reached], respectively, PFS HR, 3.2 [95% CI, 1.01 to 10.2]). Eleven patients chose a per-protocol drug holiday (range, 3.5-26.4 months) after ≥2 years of treatment; two experienced disease progression during the holiday. Nine eligible patients elected to receive bevacizumab plus atezolizumab after progressing on monotherapy; ORR was 0% and mPFS was 18.5 months (IQR, 7.9-21.1) in this small cohort. Long-term results support using atezolizumab to treat ASPS, even for several years; a drug holiday with careful monitoring may be an option for some patients.

Introduction: Online self-triage is a newer eHealth modality, and there is a paucity of research on patient adherence to self-triage recommendations. We evaluated patient compliance with online self-triage guidance to seek emergency care and compared to nurse-triage adherence rates. Methods: We reviewed primary care empaneled patients who had either nurse phone triage or an online self-triage encounter that resulted in an emergency care recommendation between January 1, 2023, and November 30, 2024. Patients triaged for mood concerns, abdominal pain, chest pain, constipation, cough, and diarrhea were included. We reviewed whether patients had an emergency department visit within 24 h of their triage encounter. For self-triage encounters, we also examined whether patients called nurse triage within 24 h of their self-triage encounter. Results: There were 689 self-triage and 2,385 nurse triage encounters with an emergency care endpoint. Adherence to the emergency care recommendation was substantially lower after self-triage (22%) than after nurse triage (61%). Patients who underwent nurse triage were significantly more likely to seek emergency care than those who self-triaged (odds ratio of 5.4 [95% CI: 4.5–6.6] p < 0.001). Both male and female patients were less likely to follow emergency care recommendations after self-triage compared to nurse triage ( p < 0.001). There were 258 patients with an emergency care endpoint from self-triage who chose to call nurse triage (median time between encounters of 16 min). Only 78 (30.2%) also received an endpoint recommendation for emergency care, and 73% of those patients sought emergency care within 24 h. Discussion: Patient compliance with online self-triage recommendations to seek emergency care was poor and significantly less than nurse triage. Follow-up calls to nurse triage led to higher compliance. Health systems using online symptom checkers should consider employing mechanisms to follow up on emergency care recommendations. Further research should elucidate factors that contribute to patients’ willingness to follow care recommendations.