Medical Specialties Commons^™

Cardiopulmonary Exercise Testing-Based Algorithm And Its Usefulness In Clinical Cardiology, Mirza Nubair Ahmad, Syed Hasan Yusuf, Rafath Ullah, Mary Ellis, Haroon Yousaf, Timothy E. Paterick, Khawaja Afzal Ammar

Journal of Patient-Centered Research and Reviews

Background: Only cardiopulmonary exercise (CPX) testing provides information on the ability of the cardiovascular system to meet the body’s metabolic demands in terms of oxygen consumption (VO₂) and carbon dioxide production (VCO₂). However, CPX testing is underutilized by cardiologists due to complex diagnostic algorithms involving up to 30 variables as well as lack of validation studies. In addition, CPX also provides oxygen (O₂) pulse as a continuous measure of stroke volume, which is its superiority to other stress modalities in which systolic function is measured at peak stress and rest. In the literature, it …

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor that is highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. The von Hippel-Lindau tumor suppressor gene is frequently mutated in ccRCC resulting in unregulated transcriptional activity of hypoxia-inducible factors (HIF) 1α and 2α. HIF-mediated transcription leads to increased growth factor expression and growth factor receptor (GFR)-mediated signaling. NFκB and STAT3 are phosphorylated in response to GFR activation and modulate gene expression, which promotes cell growth and invasion. Activated NFκB and STAT3 expression is …

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …

Score Big For Decreasing Mortality: Icd Risk Score Model, Linda Francaviglia, Rachel Petersen, Maria Stone, M. Eyman Mortada

Journal of Patient-Centered Research and Reviews

Background: Aurora Health Care, a system of 14 acute care hospitals in eastern Wisconsin, has been a long-time participant in the American College of Cardiology’s National Cardiovascular Data Registries, submitting data to its ICD Registry™ since 2005. Our system’s implantable cardioverter-defibrillator (ICD) procedure volume averages 930 cases annually. During 2012 we experienced an increase in in-hospital mortality/morbidity for ICD cases.

Purpose: A single-center study examining in-hospital mortality/morbidity post-ICD implant before and after changes in practice and patient selection.

Methods: ICD implants and generator changes discharged from January 1, 2009, to December 31, 2012, were included in developing a risk model …

Aligning Asthma Education Across The Continuum Of Physician Education: Impact On Clinical Metrics, Lisa Sullivan Vedder, Deborah Simpson, Jacob L. Bidwell, John R. Brill, Theresa Frederick

Journal of Patient-Centered Research and Reviews

Background: All trainees entering family medicine residency training programs after June 1, 2012, must complete the same American Board of Family Medicine (ABFM) Maintenance of Certification (MOC) requirements as practicing physicians. These shared requirements provide an opportunity to align physician education initiatives across the continuum focused around a clinical care topic to improve health care system metrics.

Purpose: To assess the initial effectiveness of an ABFM Asthma Part IV approved MOC module, aligned to meet residency and medical student program accreditation requirements, on health care system metrics.

Methods: An ABFM Asthma Part IV MOC module was implemented for family medicine …

Contemporary Usage Of Intra-Arterial Catheter-Directed Thrombolytic (Cdt) Power Pulse Spray With Rheolytic Thrombectomy In Failed Cdt Alone For Acute Limb Ischemia, Hani Hashim, M. Fuad Jan, Maharaj Singh, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta

Journal of Patient-Centered Research and Reviews

Background: Acute lower limb ischemia (ALI) caused by arterial embolism, thrombosis of native vessels, and/or grafts is a serious condition associated with substantial morbidity and mortality. Peripheral arterial thrombolysis utilizing catheter-directed thrombolytic (CDT) has become established as a useful option in the management of ALI. However, use and outcome of adjunctive power pulse spray with rheolytic thrombectomy (PPSRT) following unsuccessful CDT is underreported in the literature.

Purpose: To evaluate outcome of contemporary use of intra-arterial CDT PPSRT as an adjunct to unsuccessful standard CDT for ALI.

Methods: We reviewed 78 consecutive patients (mean age 69 ± 14.2 years, 48.8% female) …

Microrna Molecular Profiling From Matched Tumor And Bio-Fluids In Bladder Cancer, David A. Armstrong, Benjamin B. Green, John D. Seigne, Alan R. Schned, Carmen Marsit

Dartmouth Scholarship

MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between …

Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma

Dartmouth Scholarship

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.

Active Yap Promotes Pancreatic Cancer Cell Motility, Invasion And Tumorigenesis In A Mitotic Phosphorylation-Dependent Manner Through Lpar3., Shuping Yang, Lin Zhang, Vinee Purohit, Surendra K. Shukla, Xingcheng Chen, Fang Yu, Kai Fu, Yuanhong Chen, Joyce C. Solheim, Surendra K. Shukla, Wei Song, Jixin Dong

Journal Articles: Eppley Institute

The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. …

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Marshall Journal of Medicine

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …

Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos

Medicine Faculty Publications

Aims

To investigate the renal effects of fitness in people with diabetes with mild renal dysfunction.

Methods

The effect of a 12-week exercise programme on estimated GFR in 128 people with diabetes was evaluated.

Results

All cardiometabolic variables improved after 12 weeks of supervised exercise. Although there was a modest 3.9% increase in estimated GFR from baseline in the 128 people who completed the study, those with baseline chronic kidney disease stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01) improvements in post-exercise estimated GFR. Moreover, 42% of the people with chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after the intervention.

Conclusion

Short-term exercise improves renal function in those with more moderate baseline chronic kidney disease. …

New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen

Medicine Faculty Publications

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. …

Current Opinion In The Role Of Testosterone In The Development Of Prostate Cancer: A Dynamic Model, Xiaohui Xu, Xinguang Chen, Hui Hu, Amy B. Dailey, Brandie D. Taylor

Health Sciences Faculty Publications

Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.

Presentation of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.

Testing …

Efficacy Of Oral Anticoagulation In Stroke Prevention Among Sinus-Rhythm Patients Who Lack Left Atrial Mechanical Contraction After Cryoablation, José Martínez-Comendador, Javier Gualis, José Miguel Marcos-Vidal, Jonnatan Buber, Carlos Esteban Martín, Jesús Gomez-Plana, Miguel Angel Rodríguez, Ignacio Iglesias-Garriz, David Alonso, Carlos Soria, Eva Higuera Miguélez, Mario Castaño

The Texas Heart Institute Journal

The customary recommendation is that oral anticoagulation be withdrawn a few months after cryoablation for atrial fibrillation, independently of left atrial mechanical contraction in patients in sinus rhythm. Recently, a 5-fold increase in stroke has been described in sinus-rhythm patients who lack atrial mechanical contraction. One aim of this study was to evaluate the efficacy of oral anticoagulation in preventing postoperative stroke in such patients.

This prospective study divided 154 sinus-rhythm patients into 2 groups, depending on the presence (108 patients) or absence (46 patients) of left atrial mechanical contraction at 6 months after surgery, and monitored them annually for …

Neonatal Presentation Of An Air-Filled Neck Mass That Enlarges With Valsalva: A Case Report., Jasminkumar Bharatbhai Patel, Howard Kilbride, Lorien Paulson

Manuscripts, Articles, Book Chapters and Other Papers

Branchial cleft cysts are common causes of congenital neck masses in the pediatric population. However, neonatal presentation of branchial cleft cysts is uncommon, but recognizable secondary to acute respiratory distress from airway compression or complications secondary to infection. We report a 1-day-old infant presenting with an air-filled neck mass that enlarged with Valsalva and was not associated with respiratory distress. The infant was found to have a third branchial cleft cyst with an internal opening into the pyriform sinus. The cyst was conservatively managed with endoscopic surgical decompression and cauterization of the tract and opening. We review the embryology of …

Down Syndrome With Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, And Pulmonary Vein Stenosis, Guruprasad Mahadevaiah, Manoj Gupta, Ravi Ashwath

The Texas Heart Institute Journal

The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

Evaluation Of Previously Cannulated Radial Arteries As Patent Coronary Artery Bypass Conduits, Timothy Watson, Adele Pope, Niels Van Pelt, Peter N Ruygrok

The Texas Heart Institute Journal

In coronary artery bypass grafting, good-quality conduits are needed to maximize the potential for long-term patency. Revascularization has traditionally been achieved with use of the saphenous vein and the internal thoracic arteries. In recent years, total arterial revascularization with use of the radial arteries has been promoted. Meanwhile, use of the transradial approach for coronary angiography has also increased. The long-term effects of previous cannulation in radial artery bypass grafts are not known. Therefore, we used multidetector computed tomographic angiography to investigate radial-artery graft patency in a small series of patients who had undergone transradial angiography. We found a high …

Combined Retrograde/Antegrade Approach To Transcatheter Closure Of An Aortic Paravalvular Leak, Abdulla A Damluji, Husnu E Kaynak, Alan W Heldman

The Texas Heart Institute Journal

New interventional techniques have made transcatheter closure of aortic paravalvular leaks a viable therapeutic option to treat the sequelae of these defects, including congestive heart failure and hemolysis. We report the transcatheter closure of an aortic paravalvular leak via a combined retrograde/antegrade approach. This was necessary because of difficulty in crossing the defect with a sheath from the retrograde approach. This technique might be useful in application to other difficult structural heart interventions. To our knowledge, this is the first report of a treated paravalvular leak around a Mitroflow(®) Aortic Pericardial Heart Valve.

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian

Journal Articles: Pulmonary & Critical Care Med

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in …

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Speckle-Tracking Echocardiographic Measures Of Right Ventricular Function Correlate With Improvement In Exercise Function After Percutaneous Pulmonary Valve Implantation., Shahryar M. Chowdhury, Ziyad M. Hijazi, John T. Fahey, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to improve after transcatheter pulmonary valve implantation (TPVI). Measures of exercise function, such as ventilatory efficiency (the minute ventilation [VE]/carbon dioxide production [VCO2] slope), have been shown to be prognostic of mortality in patients who may require TPVI. The aim of this study was to evaluate the correlation between STE measures of RV function and changes in VE/VCO2 after TPVI.

METHODS: Speckle-tracking echocardiography and cardiopulmonary exercise testing were performed at baseline and 6 months after TPVI in 24 patients from four centers. Conventional echocardiographic measures of RV function were …

Commentary On "Systemic Candidiasis And Cytomegalovirus Infection In The Setting Of Artificial Cardiac Device Deployment", Moises A. Huaman

The VAD Journal

No abstract provided.

Chronic Ldh Elevation After Left Ventricular Assist Device Implantation, Hesham R. Omar, Navin Rajagopalan, Maya Guglin

The VAD Journal

A 61-year-old woman who underwent HeartMate II left ventricular assist device placement for non-ischemic cardiomyopathy developed elevated lactate dehydrogenase within two weeks after implantation. After eight months of observation and several hospital admissions during which there was no evidence of pump thrombosis, she presented with clinically manifest hemolysis. During pump exchange there was notable pannus formation on the inflow cannula of the left ventricular assist device. The pannus around the inflow likely existed for several months, limiting the flow and creating a low-grade hemolysis and this low flow state stimulated thrombus formation triggering gross hemolysis. Thoratec analysis of the pump …

Subclavian Vein Stenosis/Occlusion Following Transvenous Cardiac Pacemaker And Defibrillator Implantation: Incidence, Pathophysiology And Current Management, Brian O'Leary, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Subclavian vein stenosis is a common, but usually asymptomatic, complication following cardiac device placement. In addition to reviewing the literature on incidence, pathogenesis and management options for this important clinical problem, we describe two cases of symptomatic subclavian vein occlusion following pacemaker/defibrillator placement and successful treatment with venoplasty and stenting.

Use Of Coronary Techniques In Celiac And Hepatic Artery Stenting In Post-Hepatic Transplant Patients, Harpreet Parmar, Ryan Beard, Mark W. Mewissen, Armaan Shaikh, Tanvir Bajwa

Journal of Patient-Centered Research and Reviews

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, …

Overview Of The Role Of Duplex Ultrasound For Treatment And Surveillance Of Peripheral Arterial Disease, John H. Fish Iii, Peter Klein-Weigel, Gustav Fraedrich

Journal of Patient-Centered Research and Reviews

Imaging strategies for preinterventional planning in symptomatic peripheral artery disease have employed various modalities ranging from duplex ultrasound to noninvasive angiography with computed tomography (CT) or magnetic resonance (MRA). These methods have classically been compared to the gold standard of digital subtraction angiography and are reviewed here in detail through the work of relevant published studies and meta-analyses between 1996 and 2014. In particular, we focus on the diagnostic performance, reproducibility and cost-effectiveness of these aforementioned modalities with respect to mapping the lower extremity arterial tree for planning vascular intervention and surveillance. The data presented suggests comparable sensitivity and specificity …

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

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