A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998–2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998–2002 and 2008–2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.

Fibroblasts have different roles during physiology and disease in regulating myocardial function via soluble mediators. A crosstalk between fibroblasts and cardiomyocytes, controlled by TGF-β, is crucial in this interaction.

Previous studies investigating human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have proposed the distinction of heart chamber-specific (atrial, ventricular, pacemaker) electrophysiological phenotypes based on action potential (AP) morphology. This suggestion has been based on data acquired using techniques that allow measurements from only a small number of cells and at low seeding densities. It has also been observed that density of culture affects the properties of iPSC-CMs. Here we systematically analyze AP morphology from iPSC-CMs at two seeding densities: 60,000 cells/well (confluent monolayer) and 15,000 cells/well (sparsely-seeded) using a noninvasive optical method. The confluent cells (n = 360) demonstrate a series of AP morphologies on a normally distributed spectrum with no evidence for specific subpopulations. The AP morphologies of sparsely seeded cells (n = 32) displayed a significantly different distribution, but even in this case there is no clear evidence of chamber-specificity. Reduction in gap junction conductance using carbenoxolone only minimally affected APD distribution in confluent cells. These data suggest that iPSC-CMs possess a sui generis AP morphology, and when observed in different seeding densities may encompass any shape including those resembling chamber-specific subtypes. These results may be explained by different functional maturation due to culture conditions.

Human pluripotent stem cell‐derived cardiomyocytes (PSC‐CMs) have great potential application in almost all areas of cardiovascular research. A current major goal of the field is to build on the past success of differentiation strategies to produce CMs with the properties of those originating from the different chambers of the adult human heart. With no anatomical origin or developmental pathway to draw on, the question of how to judge the success of such approaches and assess the chamber specificity of PSC‐CMs has become increasingly important; commonly used methods have substantial limitations and are based on limited evidence to form such an assessment. In this article, we discuss the need for chamber‐specific PSC‐CMs in a number of areas as well as current approaches used to assess these cells on their likeness to those from different chambers of the heart. Furthermore, describing in detail the structural and functional features that distinguish the different chamber‐specific human adult cardiac myocytes, we propose an evidence‐based tool to aid investigators in the phenotypic characterization of differentiated PSC‐CMs. Stem Cells 2017;35:1881–1897

Background: In patients presenting with ST-segment–elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post–myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment–elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non–ST-segment–elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials. Methods and Results: We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45–1.03); P =0.07; multivessel disease following ST-segment–elevation myocardial infarction (RR, 0.84 [95% CI, 0.69–1.04]; P =0.11); non–ST-segment–elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72–0.97]; P =0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75–0.93]; P =0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53–0.90]; P =0.007) and MI (RR, 0.74 [95% CI, 0.62–0.90]; P =0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87–1.11]), cardiac death (RR, 0.89 [95% CI, 0.71–1.12]; P =0.33), or MI (RR, 0.96 [95% CI, 0.86–1.08]; P =0.54). Conclusions: PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.