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Objective: We aimed to determine whether the variability in surveillance strategies after curativeintent primary treatment of ovarian cancer is related to practitioner age. Materials and Methods: The 943 members of The Society of Gynecologic Oncology (SGO) were surveyed by conventional mail to quantify their surveillance strategies for patients with ovarian carcinoma after potentially curative initial treatment. We requested data regarding the recommended frequency of 10 commonly employed surveillance modalities. Age was used as a proxy for time since formal residency training. Results: There were 283 responders: 58 were aged 30-39, 114 were aged 40-49, 70 were aged 50-59, and 41 were aged ≥ 60. Older gynecologic oncologists (60+) ordered office visits and pelvic examinations more frequently than younger gynecologic oncologists in year 1 (p

An estimated 8–12 million Americans are believed to suffer from peripheral arterial disease (PAD) according to the American Heart Association [1]. The prevalence of PAD has been estimated at almost 10% in the general population and almost 20% in those older than 70 years. Patients with PAD present a unique challenge to the provider due to their typically older age, high rates of underdiagnosis due to asymptomatic state, and the higher prevalence of comorbid conditions. The prototypical risk factors for PAD are similar to that of coronary arterial disease and include tobacco use, hyperlipidemia, hypertension, and diabetes. The mainstay of PAD therapy is aggressive risk factor modification followed by pharmacologic therapy and exercise therapy as warranted.

Background The diagnosis of metabolic syndrome indicates a clustering of metabolic imbalances which in sum have been recognized as a major predictor of cardiovascular and all-cause mortality. The aim of this study was to assess the level of under-pharmacy and poly-pharmacy and its prognostic impact in elderly patients with metabolic syndrome.

Major perioperative cardiac events are estimated to complicate between 1.4% and 3.9% of surgeries. Because most surgeries are elective, there is the opportunity to implement strategies to reduce this risk. Accurate identification of patients at risk for such events will allow patients to be better informed about the benefit-to-risk ratio of procedures, and guide allotment of limited clinical resources, utilization of preventive interventions, and areas of future research. This review focuses on important features of the initial pre-operative clinical risk assessment, indications for diagnostic testing to quantify cardiac risk, and the methods and indications for pre-emptive therapies.

Historically, medicine has been warned, “first, do no harm.” In contemporary practice, however, the emergency response has generally been to err on the side of action with resuscitation efforts. Typically, it is only later on when medical therapy is considered futile that treatment is withdrawn. In such circumstances, a do-not-resuscitate (DNR) order is typically enacted as a part of an advance directive. However, when such patients attempt suicide, the approach to their care becomes complicated. Is the DNR order valid in a suicidal patient? What is the role of patient autonomy? How should an ethics consultant advise? This case details the method by which such issues should be approached in the emergent care of patients who have DNR order and attempt suicide.

Acute type B aortic dissection comprises approximately one-third of all aortic dissection cases. Although this catastrophic cardiovascular condition was first described in the medical literature over two centuries ago, data on the optimal diagnostic and treatment modalities for type B dissection was slow to evolve throughout the latter half of the twentieth century, even as newer diagnostic techniques and management strategies became commonplace. To further elucidate contemporary practice patterns and outcomes of aortic dissection, the International Registry of Acute Aortic Dissection (IRAD) was established in 1996. Over the past two decades, IRAD publications have steadily increased our knowledge and understanding about aortic dissection. Specifically in recent years, analyses of IRAD data have gone beyond simply characterizing the patient with acute type B aortic dissection and have attempted to identify the means by which the outcome of such a patient could be improved. Thus, we present herein three areas in which IRAD data has recently advanced our understanding of acute type B aortic dissection: temporal classification especially for the subacute time period, risk stratification for identifying complicated cases, and thoracic endovascular aortic repair (TEVAR).

Background— Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Methods and Results— Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis -gene regulation represents a major mechanism of action of human cardiac lncRNAs. Conclusions— The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

Background Despite extensive attention dedicated to transcatheter aortic valve replacement (TAVR) in both the medical literature and lay press, little is known about the anticipated utilization of TAVR by the US cardiology community. Hypothesis TAVR use is likely to outstrip its initial clinical indications. Methods Four days after approval of the first TAVR device in November 2011 by the US Food and Drug Administration, we emailed an online questionnaire to 201 authors of major TAVR clinical trials (trialists) and 461 recent members of an interventional cardiology professional society (clinicians). Responses were compared using χ2, t tests, and analysis of variance. Results Of 205 surveys received (response rate 31%; 114 clinicians, 91 trialists), the majority of respondents were interventionalists (86%) working in academic practices (72%). Although most physicians anticipated referring

Translational studies that assess and extend observations made in animal models of human pathology to elucidate relevant and important determinants of human diseases require the availability of viable human tissue samples. However, there are a number of technical and practical obstacles that must be overcome in order to perform cellular and electrophysiological studies of the human heart. In addition, changing paradigms of how diseases are diagnosed, studied and treated require increasingly complex integration of rigorous disease phenotyping, tissue characterization and detailed delineation of a multitude of “_omics”. Realizing the need for quality‐controlled human cardiovascular tissue acquisition, annotation, biobanking and distribution, we established the Translational Cardiovascular Biobank & Repository at Washington University School of Medicine. Several critical details are essential for the success of cardiovascular biobanking including coordinated, trained and dedicated staff members; adequate, nonrestrictive informed consent protocols; and fully integrated clinical data management applications for annotating, tracking and sharing of tissue and data resources. Labor and capital investments into growing biobanking resources will facilitate collaborative efforts aimed at limiting morbidity and mortality due to heart disease and improving overall cardiovascular health.

Transcatheter aortic valve replacement (TAVR) is the first major addition to the treatment of valvular heart disease in more than a decade, and the number of patients eligible for valve replacement is likely to increase significantly. As a consequence, little is known about expectations within the

Cells lacking ataxia telangiectasia mutated (ATM) have impaired mitochondrial function. Furthermore, mammalian cells lacking ATM have increased levels of reactive oxygen species (ROS) as well as mitochondrial DNA (mtDNA) deletions in the region encoding for cytochrome c oxidase (COX). We hypothesized that ATM specifically influences COX activity in skeletal muscle. COX activity was ∼40% lower in tibialis anterior from ATM-deficient mice than for wild-type mice (P < 0.01, n = 9/group). However, there were no ATM-related differences in activity of succinate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, or complex III. Incubation of wild-type extensor digitorum longus muscles for 1h with the ATM inhibitor KU55933 caused a ∼50% reduction (P

Background There is little published evidence regarding intraoperative and postoperative complications in patients with ventriculoperitoneal shunts who undergo cholecystectomy. Methods Nationwide Department of Veterans Affairs databases were searched to identify patients with International Classification of Diseases, 9th revision, Clinical Modification codes for a VP shunt who later had a cholecystectomy during fiscal years 1994 to 2003. Charts on these patients were obtained and reviewed. Results Twenty-three patients were deemed evaluable. Of these, 8 had laparoscopic converted to open cholecystectomies. All conversions were owing to dense adhesions. There were 2 cases of postoperative shunt infection that required shunt removal and replacement. Conclusions The rate of conversion from laparoscopic to open cholecystectomy was 57% in this study, significantly higher than the reported rate of conversion for patients without shunts in Department of Veterans Affairs Medical Centers (5%). Cholecystectomy in adult patients with a preexisting ventriculoperitoneal shunt appears to result in a shunt infection rate similar to that reported after shunt insertion or revision.

Ataxia telangiectasia mutated (ATM) reportedly plays a role in insulin-stimulated activation of Akt in some cell types but not in others. The role of ATM in insulin signalling has not been firmly resolved for skeletal muscle cells, for which Akt phosphorylation is a pivotal step in stimulation of glucose transport. Accordingly, our aim was to determine the role of ATM in insulin effects for cell lines derived from skeletal muscle and for skeletal muscle.We examined insulin effects in L6 myotubes, mouse soleus, C2C12 myotubes and differentiated rhabdomyosarcoma (RD) cells in the presence and absence of a low concentration (1 microm) of the ATM inhibitor KU55933. We also compared insulin signalling in C2C12 cells expressing shRNA against ATM and control cell lines (empty vector; cells expressing non-targeting shRNA).In L6 myotubes and mouse soleus muscle, KU55933 inhibited insulin-stimulated phosphorylation of the 160 kDa substrate of Akt (AS160) despite no effect on Akt. In contrast, KU55933 prevented insulin-stimulated Akt phosphorylation in C2C12 myotubes. Furthermore, C2C12 myotubes expressing shRNA against ATM displayed reduced insulin-stimulated Akt phosphorylation compared to controls. KU55933 also decreased insulin-stimulated Akt phosphorylation in differentiated RD cells.These model-dependent differences in the role of ATM in insulin action demonstrate a role of ATM in insulin-stimulated phosphorylation of Akt (in C2C12 and RD cells) but also allow the elucidation of a novel, Akt-independent role of ATM (in L6 myotubes and mouse soleus, at the level of AS160) in insulin signalling.

Introduction: Cardiac markers are frequently checked in patients presenting with atrial fibrillation (AF) and rapid ventricular rate (RVR). Clinical significance of mild troponin elevation in this setting and clinical value of this practice is not well known. It has been suggested that mild troponin elevation in this setting represents rate related demand ischemia and not ACS. Hypothesis: We hypothesized that measuring Troponin in AF/ RVR without signs/ symptoms of myocardial infarction has low yield and limited clinical value in predicting cardiovascular events. Method: Multi-center, retrospective cohort study of 452 subjects (age 67±14, M:F=4:1) presenting with AF/ RVR between 2000 and 2006. Occurrence of MI at one year after discharge was primary outcome. Results: Of all cases presenting with A fib/ RVR, Troponin was checked in 351 cases (77.7%). Of these 197 (age 70±11, M:F=7.1) had elevated Troponin(group-I) and 154 (age 61±16, M:F=1.1) had a normal Troponin (group-II) (1.4±5.3 vs 0.02±0.01 ng/ml, P=0.003). Group-I was older with more renal failure compared to group-II (P=0.0001, 0.0001, 0.0002 respectively). However, there was no difference in the rate of diabetes, anemia and symptom of chest pain at the time of presentation (P=0.9, 0.07 and 0.058 respectively). There was no significant difference in ventricular rate (123+31vs 123+33, P=0.3), duration of symptoms (61±186.6 vs 30.3±46.1 h , P=0.2), and ST-T changes (38(21%) vs 38 (28%) P=0.8) between two groups. During hospitalization, 76(38.6%) stress tests were performed on subjects in group-I vs. 48(31%) in group-II (p=0.17). These stress tests led to 37(48.7%) vs 12(25%) coronary angiographies (P=0.013). In group-I at one year follow up, 15 (7%) of subjects developed MI, but none in group-II. Based on these data, Troponin has sensitivity, specificity, positive and negative predictive values of 84.6%, 27.8%, 29.7% and 83.3% respectively for detecting coronary disease in A Fib weith RVR and 100%, 45.8%, 7.6% and 100% respectively for occurrence of MI in one year. Conclusion: Even mild troponin elevation in the setting of AFib with RVR predicts a significant increase in risk of MI at 1 yr. A normal Troponin in this setting is predictive of a favorable cardiovascular outcome at one year.

9110 Background: Although the management of potentially curable breast cancer is well standardized, the optimal regimen to monitor patients after initial therapy is less clear. The purpose of the c...