Citations

PURPOSE Phyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary. METHODS We performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR). RESULTS Of 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial negative margin (82.4% with < 2 mm), and 157 with an initial positive margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did not undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm v < 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; P = .27) or final margin status (positive v negative: OR = 0.96; 95% CI, 0.26 to 3.52; P = .96). CONCLUSION In current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR.

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

Abstract Introduction Given the potential side effects and the lack of data on its efficacy, the role of statins in the very elderly (age 75+) with peripheral arterial disease (PAD) is uncertain. Previous studies have shown significant mortality benefit in very elderly patients with coronary artery disease, but the effect in PAD has not been evaluated. Methods Very elderly patients aged 75 to 80 with at least five years of follow-up who underwent ankle-brachial index (ABI) measurement were included. PAD was defined as either low ABI &lt;0.90 or high ABI &gt;1.40. Demographic, medication use, comorbidity and mortality data was obtained using the electronic medical record. Univariate and multivariate Cox proportional hazard analyses were performed. Results In total, 4,560 very elderly subjects with PAD were included in the analysis. The median age was 77 (interquartile range 76–79) and 39% were female. 3,462 (76%) had low ABI while 1098 (24%) had high ABI. Univariate analysis showed that patients on statins were more likely to be male, have diabetes, have coronary artery disease, and have hyperlipidemia. Overall, 1,355 (30%) patients died in the five-year period. Unadjusted all-cause mortality hazard ratios for patients with low or high ABI with statin use was 0.66 (95% confidence interval [CI]: 0.57–0.75) and 0.80 (95% CI: 0.66–0.97), respectively. After adjusting for age, sex, coronary artery disease and diabetes, statin use in low and high ABI was still associated with significant reductions in risk of all-cause mortality of 0.59 (95% CI: 0.51–0.67) and 0.66 (95% CI: 0.54–0.80), respectively. The survival curve for very elderly patients with PAD by statin use is shown in Figure 1. Conclusion Statin use in the very elderly was associated with lower risk of all-cause mortality in the five-year period after diagnosis of PAD. There appears to be a mortality benefit with statin use in the very elderly with PAD, though careful consideration of benefits and side effects should be individualized in this age group. Figure 1 Funding Acknowledgement Type of funding source: None

AbstractIntroductionThe need for transparency in financial relationships in the healthcare system, has culminated in Open Payments database, managed by the Center for Medicare and Medicaid Services (CMS). Since its inception in 2013, the trend in such payments to physicians practicing cardiac electrophysiology was not examined.Methods and ResultsPayment information reported to CMS from January 2013 to December 2018 was obtained from the publicly available Open Payments data set using the online query tool. The data were analyzed by an individual provider and by state. An in‐depth analysis of payments in the year 2018 payments was performed. From 2014 to 2018, there was an 18% increase in the total number of payments reported from 88 877 payments in 2014 to 105 000 in 2018. Despite the increase in the total number of payments reported, the average payment steadily decreased over time, resulting in an overall reduction in the total amount of payments from 2014 to 2018 ($34.9 million to $28.2 million). Payments to the top 5% of individual recipients have also decreased over this time. In 2018, 2888 unique providers received reportable payments, a total of 105 000 payments, with a median payment amount of $1378 (interquartile range: $165–$5781). The majority of these payments were for food and beverage (82%) and travel/lodging (10%). The top five payers include Boston Scientific, Medtronic Vascular, Abbott Laboratories, Janssen Pharmaceuticals, and Biotronik.ConclusionAmong cardiac electrophysiologists, there is increased reporting of payments in the Open Payments program over time, with a notable decrease in the payment amount.

Abstract Background Coronary artery disease (CAD) and atrial fibrillation (AF) are commonly associated. Co-treatment with multiple anti-thrombotic agents can increase the risk of bleeding. Purpose We sought to evaluate patient-centered outcomes in patients with AF on double therapy with direct oral anticoagulants (DOACs) compared to patients with standard triple therapy, [a vitamin K antagonist (VKA) plus dual antiplatelet therapy]. Methods We performed an extensive systematic review of the literature and meta-analysis of randomized controlled trials reporting outcomes of patients receiving double therapy with DOACs compared to triple therapy with VKAs in patients with AF undergoing percutaneous coronary intervention (PCI). Patient-centered outcomes were the International Society of Thrombosis and Hemostasis (ISTH) major or clinically relevant non-major bleeding (CRNB), all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction, stent thrombosis, and stroke. Results Four randomized controlled trials (9602 patients) met our inclusion criteria. Compared to VKAs, DOACs were associated with significantly lower ISTH major bleeding/ CRNB (RR - 0.75, 95% CI: 0.67-0.82, p &lt; 0.00001, I2 = 11%). There were no statistically significant differences in the efficacy outcomes, including myocardial infarction (RR- 0.99, 95% CI :0.79-1.25, p = 0.96, I2 = 0%), stent thrombosis (RR - 0.97, 95% CI: 0.6-1.55, p = 0.89, I2 = 0%), ischemic stroke (RR - 0.76, 95% CI: 0.5-1.15, p = 0.19, I2 = 0%), all-cause mortality (RR - 1.06, 95% CI: 0.85-1.31, p = 0.61, I2 = 0%) and MACE (RR - 1.06, 95% CI: 0.91-1.22, p = 0.97, I2 = 0%). Conclusion Compared with triple therapy with VKAS, double therapy with DOACs is associated with a reduced risk of bleeding and is as effective in patients with AF undergoing PCI. Abstract Figure.

Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with &gt;95% accuracy that was maintained in all analytic and biological validations. Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271