Faculty Bibliography

IMPORTANCE:The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. OBJECTIVE:To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. DESIGN, SETTING, AND PARTICIPANTS:The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). MAIN OUTCOMES AND MEASURES:Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. RESULTS:A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001). CONCLUSIONS AND RELEVANCE:These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.

BACKGROUND:The healthcare burden posed by the coronavirus disease 2019 (COVID-19) pandemic in the New York Metropolitan area has necessitated the postponement of elective procedures resulting in a marked reduction in cardiac catheterization laboratory (CCL) volumes with a potential to impact interventional cardiology (IC) fellowship training. METHODS:We conducted a web-based survey sent electronically to 21 Accreditation Council for Graduate Medical Education accredited IC fellowship program directors (PDs) and their respective fellows. RESULTS:Fourteen programs (67%) responded to the survey and all acknowledged a significant decrease in CCL procedural volumes. More than half of the PDs reported part of their CCL being converted to inpatient units and IC fellows being redeployed to COVID-19 related duties. More than two-thirds of PDs believed that the COVID-19 pandemic would have a moderate (57%) or severe (14%) adverse impact on IC fellowship training, and 21% of the PDs expected their current fellows' average percutaneous coronary intervention (PCI) volume to be below 250. Of 25 IC fellow respondents, 95% expressed concern that the pandemic would have a moderate (72%) or severe (24%) adverse impact on their fellowship training, and nearly one-fourth of fellows reported performing fewer than 250 PCIs as of March 1st. Finally, roughly one-third of PDs and IC fellows felt that there should be consideration of an extension of fellowship training or a period of early career mentorship after fellowship. CONCLUSIONS:The COVID-19 pandemic has caused a significant reduction in CCL procedural volumes that is impacting IC fellowship training in the NY metropolitan area. These results should inform professional societies and accreditation bodies to offer tailored opportunities for remediation of affected trainees.

Transcriptomic profiling classifies pancreatic ductal adenocarcinoma (PDAC) into several molecular subtypes with distinctive histological and clinical characteristics. However, little is known about the molecular mechanisms that define each subtype and their correlation with clinical outcome. Mutant KRAS is the most prominent driver in PDAC, present in over 90% of tumors, but the dependence of tumors on oncogenic KRAS signaling varies between subtypes. In particular, squamous subtype are relatively independent of oncogenic KRAS signaling and typically display much more aggressive clinical behavior versus progenitor subtype. Here, we identified that YAP1 activation is enriched in the squamous subtype and associated with poor prognosis. Activation of YAP1 in progenitor subtype cancer cells profoundly enhanced malignant phenotypes and transformed progenitor subtype cells into squamous subtype. Conversely, depletion of YAP1 specifically suppressed tumorigenicity of squamous subtype PDAC cells. Mechanistically, we uncovered a significant positive correlation between WNT5A expression and the YAP1 activity in human PDAC, and demonstrated that WNT5A overexpression led to YAP1 activation and recapitulated YAP1-dependent but Kras-independent phenotype of tumor progression and maintenance. Thus, our study identifies YAP1 oncogene as a major driver of squamous subtype PDAC and uncovers the role of WNT5A in driving PDAC malignancy through activation of the YAP pathway.

Global disparities in the quantity, distribution, and skills of health workers worldwide pose a threat to attainment of the Sustainable Development Goals by 2030 and deepens already existing global health inequities. Rwanda and other low-resource countries face a critical shortage of health professionals, particularly nurses and midwives. This article describes the Human Resources for Health (HRH) Program in Rwanda, a collaboration between the Ministry of Health of Rwanda and a U.S. consortium of academic institutions. The ultimate goal of the HRH Program is to strengthen health service delivery and to achieve health equity for the poor. The aim of this article is to highlight the HRH nursing and midwifery contributions to capacity building in academic and clinical educational programs throughout Rwanda. International academic partnerships need to align with the priorities of the host country, integrate the strengths of available resources, and encourage a collaborative environment of cultural humility and self-awareness for all participants.

BACKGROUND: Same-day discharge after percutaneous coronary intervention (PCI) may be safe for some patients. Few data are available on patient-reported outcomes and preferences for same-day discharge after PCI. METHODS AND RESULTS: Between March 2008 and March 2010, a total of 298 patients undergoing elective PCI via femoral access at 2 medical centers (Mount Sinai Hospital, New York, NY, and Baylor Medical Center, Dallas, TX) were randomized to same-day (n=150) or next-day (n=148) discharge. The primary outcome was high patient coping during the 7 days after discharge defined as scores <20 on the validated postdischarge coping difficulty scale. Safety outcomes, clopidogrel adherence, and patient preferences were secondary outcomes. Before discharge, patients randomized to same-day and next-day discharge were similar with respect to sociodemographic and clinical characteristics. High-coping ability, assessed 7 days after PCI, was present for 79% of patients randomized to same-day discharge and for 77% of patients randomized to next-day discharge. The difference in high coping ability, 2 (95% confidence interval, -7 to 11), did not cross the noninferiority threshold of -12% (P<0.001 that same-day discharge is not noninferior to next-day discharge). At 30 days after PCI, clopidogrel adherence, physician and emergency room visits, and hospitalization were similar in the 2 randomization groups. In addition, 80% and 68% of those randomized to same-day and next-day discharge, respectively, stated they would prefer same-day discharge if they were to have another PCI procedure. CONCLUSIONS: Same-day discharge after PCI was associated with patient-reported and clinical outcomes similar to those of next-day discharge and was preferred by most patients.

Left main coronary artery (LMCA) disease remains an important risk factor for increased mortality and morbidity at all stages of diagnosis and treatment of coronary artery disease. Left main stem pathology is often silent, with unpredictable presentation: as such it poses diagnostic and management challenges. This article reviews the anatomy, epidemiology and diagnosis of left main stem disease, as well as advances in multidisciplinary concepts of diagnosis and management, and summarises the outcomes of recent prospective studies comparing percutaneous and surgical revascularisation in LMCA disease.

OBJECTIVES: This study evaluated the outcomes of patients discharged the day of percutaneous coronary intervention (PCI) by analyzing the data from a single-center, large, multioperator registry of interventions. BACKGROUND: Although same-day discharge is likely safe after interventions on low-risk stable patients, there is limited data to guide selection of a broader population of patients. Due to numerous patient variables and physician preferences, standardization of the length of stay after PCI has been a challenge. Most of the reported studies on same-day discharge have strict inclusion criteria and hence do not truly reflect a real-world population. METHODS: We analyzed the outcomes of consecutive same-day discharge in 2,400 of 16,585 patients who underwent elective PCI without any procedural or hospital complication. Composite end point included 30-day major adverse cardiac cerebral events and bleeding/vascular complications. RESULTS: The mean age of the study population was 57.0 +/- 23.7 years with 12% aged over 65 years. Twenty-eight percent received glycoprotein IIb/IIIa inhibitor with closure devices in 90.5%. Clinical and angiographic success was noted in 97% of all PCIs. The average length-of-stay following PCI was 8.2 +/- 2.5 h. The composite end point was reached in 23 patients (0.96%). Major adverse cardiac cerebral events occurred in 8 patients (0.33%) and vascular/bleeding complications in the form of Thrombolysis In Myocardial Infarction minor bleeding in 14 patients (0.58%) and pseudoaneurysm in 1 patient (0.04%). CONCLUSIONS: When appropriately selected, with strict adherence to the set protocol, same-day discharge after uncomplicated elective PCI is safe despite using femoral access in a wide spectrum of patients.

OBJECTIVES: We studied the use of 8 Fr Angio-Seal in closure of access sites up to 10 Fr. BACKGROUND: The use of larger French catheters for procedures such as valvuloplasty and percutaneous valve replacement has required the use of better methods for arterial closure. The use of 6 and 8 Fr Angio-Seal hemostatic devices (St. Jude Medical, St. Paul, Minnesota) has been well described and are routinely used for diagnostic and interventional procedures up to 8 Fr in size. However, no data are available for the use of an 8 Fr Angio-Seal device in the closure of access sites up to 10 Fr. METHODS: In our center, we evaluate the incidence of vascular complications following the use of an 8 Fr Angio-Seal device with 10 Fr sheaths in patients undergoing aortic valvuloplasty. RESULTS: Of 53 procedures, there was only 1 vascular complication, a ruptured pseudoaneurysm, which required vascular repair. CONCLUSIONS: Our data suggest that an 8 Fr Angio-Seal device can be utilized effectively and safely in procedures requiring larger access sites up to 10 Fr.

Edge restenosis (candy wrapper effect) and late thrombosis remain a problem in various randomized intracoronary brachytherapy (ICBT) trials for the treatment of in-stent restenosis (ISR). Target vessel revascularization (TVR) due to target lesion revascularization (TLR) and edge restenosis can be decreased with the use of longer ICBT sources and debulking devices and has not been systematically studied. We analyzed 226 patients with ISR (240 vessels of 264 lesions; average lesion length 17.5+/-8.9 mm) who had lesion debulking followed by 90 Strontium (Sr) beta-irradiation using the Novoste Betacath system (30 mm source in 144 vessels and 40 mm source in 96 vessels). Dual antiplatelet therapy was recommended for one year. At follow-up of 12+/-2 months, clinical TVR occurred in 9.7%, with TLR in 7.1% and non-TLR in 2.6% of cases. There was no delayed or late subacute thrombosis. Beta-irradiation using a longer 90Sr source after lesion modification with cutting balloon (CB) and or rotational atherectomy (RA), along with the use of long-term dual antiplatelet therapy is safe and associated with single-digit clinical restenosis.