The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

Are All Cysts Created Equal?: Pancreatic Cystic Neoplasms in Patients with Familial or Genetic Risk Factors for Pancreatic Cancer.

Pancreatic cystic lesions (PCLs) have become more prevalent over time, particularly in asymptomatic individuals. Current screening guidelines for incidental PCLs offer a unified approach to surveillance and management, predicated on "worrisome features." Although PCLs are common in the general population, their prevalence may be higher in high-risk individuals (HRI, unaffected patients with specific familial and/or genetic risk factors). As more PCLs are diagnosed and more HRI identified, it is important to promote research that bridges data gaps and introduces nuance to risk assessment tools, ensuring tailoring of guidelines to the needs of HRI with varying pancreatic cancer risk factors.

Meta-Analysis of Gender Disparities in In-hospital Care and Outcomes in Patients with ST-Segment Elevation Myocardial Infarction.

Gender disparities in ST-segment elevation myocardial infarction (STEMI) outcomes continue to be reported worldwide; however, the magnitude of this gap remains unknown. To evaluate gender-based discrepancies in clinical outcomes and identify the primary driving factors a global meta-analysis was performed. Studies were selected if they included all comers with STEMI, reported gender specific patient characteristics, treatments, and outcomes, according to the registered PROSPERO protocol: CRD42020161469. A total of 56 studies (705,098 patients, 31% females) were included. Females were older, had more comorbidities and received less antiplatelet therapy and primary percutaneous coronary intervention (PCI). Females experienced significantly longer delays to first medical contact (mean difference 42.5 min) and door-to-balloon time (mean difference 4.9 min). In-hospital, females had increased rates of mortality (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.84 to 1.99, p <0.00001), repeat myocardial infarction (MI) (OR 1.25, 95% CI 1.00 to 1.56, p=0.05), stroke (OR 1.67, 95% CI 1.27 to 2.20, p <0.001), and major bleeding (OR 1.82, 95% CI 1.56 to 2.12, p <0.00001) compared with males. Older age at presentation was the primary driver of excess mortality in females, although other factors including lower rates of primary PCI and aspirin usage, and longer door-to-balloon times contributed. In contrast, excess rates of repeat MI and stroke in females appeared to be driven, at least in part, by lower use of primary PCI and P2Y12 inhibitors, respectively. In conclusion, despite improvements in STEMI care, women continue to have in-hospital rates of mortality, repeat MI, stroke, and major bleeding up to 2-fold higher than men. Gender disparities in in-hospital outcomes can largely be explained by age differences at presentation but comorbidities, delays to care and suboptimal treatment experienced by women may contribute to the gender gap.

Sex disparities in acute myocardial infarction care and outcomes.

AIM: We investigated sex-based and regional outcomes after contemporary percutaneous coronary intervention (PCI) with the Xience V stent in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: This patient level pooled analysis includes three multi-center, prospective post-market registries performed in the US, Japan, and China. A total of 1,938 patients treated with Xience V stents in the setting of AMI were enrolled. Compared to men, women had higher major adverse cardiac events (MACE) (14.1% vs. 9.8% P < 0.01, RR 1.4, 95% CI 1.1-1.4) and all-cause mortality (10% vs. 6.2% P < 0.01, RR 1.61, 95% CI 1.14-2.27) at one year, without any significant difference in device specific outcomes of target vessel failure (TVF). US patients compared to the patients from China and Japan had increased MACE (female: 18% vs. 7.1%, P = 0.0012, male: 15.7% vs. 4.1%, P < 0.0001). Multivariable analysis demonstrated that major bleeding was the strongest predictor of MACE (OR 10.51, 95%CI 4.01-27.50, P < 0.0001), MI (OR 4.26, 95%CI 1.37-13.29, P = 0.012), and all-cause death (OR 5.3, 95%CI 2.32-12.13, P < 0.0001). CONCLUSION: Women with AMI who underwent PCI with XIENCE DES have higher all-cause mortality at one year in compared to men. Region based outcomes demonstrated increased MACE among US patients compared to the patients from China and Japan. After adjusting for differences in demographics, major bleeding, rather than female sex, predicted the higher observed all-cause mortality.

FoxO transcription factors are required for hepatic HDL cholesterol clearance.

Insulin resistance and type 2 diabetes are associated with low levels of high-density lipoprotein cholesterol (HDL-C). The insulin-repressible FoxO transcription factors are potential mediators of the effect of insulin on HDL-C. FoxOs mediate a substantial portion of insulin-regulated transcription, and poor FoxO repression is thought to contribute to the excessive glucose production in diabetes. In this work, we show that mice with liver-specific triple FoxO knockout (L-FoxO1,3,4), which are known to have reduced hepatic glucose production, also have increased HDL-C. This was associated with decreased expression of the HDL-C clearance factors scavenger receptor class B type I (SR-BI) and hepatic lipase and defective selective uptake of HDL cholesteryl ester by the liver. The phenotype could be rescued by re-expression of SR-BI. These findings demonstrate that hepatic FoxOs are required for cholesterol homeostasis and HDL-mediated reverse cholesterol transport to the liver.

Clinical outcomes after PCI treatment of very long lesions with the XIENCE V everolimus eluting stent; Pooled analysis from the SPIRIT and XIENCE V USA prospective multicenter trials.

BACKGROUND: Lesion length has been an important factor in predicting a worse outcome after percutaneous coronary interventions (PCI); however, the safety and efficacy of second-generation drug eluting stents in very long coronary lesions has not been validated in large scale randomized controlled trials. METHODS: We performed a patient level pooled analysis of 13,266 patients undergoing planned overlapping stent treatment of very long coronary lesions with the XIENCE V everolimus eluting coronary stent system from 6 trials evaluating the XIENCE V stent (Spirit II, III, IV, V, Spirit Small Vessel and XIENCE V USA). Patients were divided into two cohorts, a very long lesion (VLL) group (lesions ≥35 mm) and a control group (lesions >24 to <35 mm). The primary outcome measures were Target Lesion Failure (TLF), Major Adverse Cardiac Events (MACE), and Academic Research Consortium (ARC) defined definite and probable stent thrombosis at 1 year. RESULTS: A total of 13,266 patients were included in the pooled analysis of which 2.4% (323 patients with 328 total lesions) had a mean lesion length of 47.1 ± 13.7 mm in the VLL group which were compared to controls comprised of 3.6% of the cohort (482 patients with 500 total lesions) with mean lesion length of 28.1 ± 2.4 mm.There was no significant difference in the rates of TLF between the VVL and control groups (8.9 vs. 10%, P = 0.63), MACE (9.2 vs. 10%, P = 0.74) or stent thrombosis (1.6 vs. 1.5%, P = 0.92) at 1 year. CONCLUSIONS: In the treatment of very long coronary lesions, the XIENCE V stent appears as safe and effective as percutaneous coronary interventions for long lesions. © 2016 Wiley Periodicals, Inc.