Medicine and Health Sciences Commons^™

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations & Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations & Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Role Of Nudt21 Mediated Alternative Polyadenylation And Hyaluronan In The Development Of Pulmonary Hypertension, Scott Dale Collum

Dissertations & Theses (Open Access)

Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that …

Goosebumps, Efrain Rodriguez

The Texas Heart Institute Journal

No abstract provided.

Surgical Thrombectomy For Pulmonary Embolism: Updated Performance Rates And Outcomes, Fahad Alqahtani, Muhammad Bilal Munir, Sami Aljohani, Abdul Tarabishy, Ahmad Almustafa, Mohamad Alkhouli

The Texas Heart Institute Journal

Treatments for pulmonary embolism are numerous and often complex. Current data on surgical thrombectomy are important but are not readily available. We studied the National Inpatient Sample to evaluate trends in the performance rates and outcomes of surgical thrombectomy in the United States from 2003 through 2014. We think that our findings have meaningful application to the triage and risk stratification of patients who have hemodynamically significant pulmonary embolism.

Incidence And Predictors Of Obstructive Coronary Artery Disease And The Role Of Cardiac Troponin Assays In Patients With Unstable Angina, Sushan Yang, Nirmanmoh Bhatia, Meng Xu, John A Mcpherson

The Texas Heart Institute Journal

In a time when cardiac troponin assays are widely used to detect myocardial injury, data remain scarce concerning the incidence and predictors of substantial obstructive coronary artery disease that causes unstable angina. This retrospective single-center study included consecutive patients hospitalized for unstable angina from January 2015 through January 2016. Patients with troponin I levels above the upper reference limit and those who did not undergo angiography were excluded. Multivariate logistic regression analysis was used to identify predictors of obstructive coronary artery disease that warranted revascularization and of major adverse cardiac events up to 6 months after discharge from the hospital. …

Adam Christian Thebesius' Channels Into The Human Heart: The Thebesian Veins And The Thebesian Valve, Magdalena Mazurak, Jacek Kusa

The Texas Heart Institute Journal

In 1708, Adam Christian Thebesius, a 22-year-old student at Leiden University, presented his graduate thesis, Disputatio medica inauguralis de circulo sanguinis in corde. More than a doctoral dissertation, this groundbreaking work opened new channels into the study of the human coronary venous system. Thebesius' theory about the vascular communication between the coronary arteries and the chambers of the heart helped to advance understanding of hemodynamic principles and to clarify the physiologic pathways of the coronary circulation. The following article—the third in a trilogy about Lower Silesian scientists—provides an overview of the life story and achievements of this Silesian physician …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

Endoanchors Minimize Endoleaks In Chimney-Graft Endovascular Repair Of Juxtarenal Abdominal Aortic Aneurysms, Edgar Luis Galiñanes, Eduardo A Hernandez-Vila, Zvonimir Krajcer

The Texas Heart Institute Journal

Juxtarenal abdominal aortic aneurysms (AAAs) are difficult to treat because they often have little or no proximal aortic neck. Patients with this complex anatomy are not usually candidates for an endovascular aneurysm repair (EVAR). Chimney-graft EVAR has been introduced, but type Ia endoleak is a typical risk. We have begun using EndoAnchors to determine whether this risk can be reduced. From July 2013 through July 2014, we used the chimney-graft EVAR technique in 5 patients whose juxtarenal AAAs had a short or no proximal aortic neck. During the procedure, we implanted EndoAnchors as needed. Postprocedurally, at 30 days, and through …

Osborn Waves: Differential Diagnosis, Akriti G Jain, Hammad Zafar, Sanjay Jain, Jason D'Souza

The Texas Heart Institute Journal

No abstract provided.

Anomalous Origin Of The Right Coronary Artery From The Pulmonary Artery In A Neonate With Turner Syndrome And Aortic Arch Hypoplasia, Bryan P Stefek, Jason R Imundo, Joseph B Clark

The Texas Heart Institute Journal

Anomalous origin of the right coronary artery from the pulmonary artery, a rare congenital cardiac defect, is typically not diagnosed during infancy. On the other hand, Turner syndrome is usually diagnosed early, and it is classically associated with bicuspid aortic valve and aortic coarctation. Individuals with Turner syndrome are also at increased risk for coronary artery anomalies. We present a case of anomalous right coronary artery from the pulmonary artery in a week-old neonate who also had Turner syndrome, patent ductus arteriosus, transverse aortic arch hypoplasia, and impaired ventricular function. Prostaglandin therapy through the ductus increased the patient's myocardial perfusion. …

Percutaneous Coronary Intervention For Interposed Coronary Graft Stenosis After Modified Bentall Procedure In A Teenaged Boy With Takayasu Arteritis, Hiroki Ikenaga, Satoshi Kurisu, Yasuki Kihara

The Texas Heart Institute Journal

Anastomotic occlusion of an interposed coronary artery graft after a Bentall procedure is rare and catastrophic. It can lead to myocardial infarction or sudden cardiac death. We found several reports of occlusion and stenosis of a coronary-graft anastomosis, but few describe occlusion of the interposed coronary graft itself, as evaluated with use of intracoronary ultrasonography and computed tomography. We report the case of a 17-year-old boy with Takayasu arteritis who had a myocardial infarction caused by severe ostial stenosis in an interposed left coronary graft. The graft occlusion was confirmed by results of electrocardiography, aortography, and intracoronary ultrasonography. The patient …

Metabolic Control, Quality Of Life, And Body Image In Patients With Glycogen Storage Disease Type Ia, Alexa Bream

Dissertations & Theses (Open Access)

Glycogen storage disease is a group of inborn errors of metabolism, with type Ia being the most common form of the disorder. Glycogen storage disease type Ia (GSDIa) is a multisystemic condition in which individuals have various complications secondary to an inability to properly break down glycogen and to perform gluconeogenesis. Complex management is then necessary for patients and includes dietary modification, frequent cornstarch usage, and evaluation for additional complications such as hepatic adenomas, hypertriglyceridemia, and kidney disease. Previous studies have found lower scores in quality of life and body image in GSDIa patients; however, the specific factors influencing this …

Effectiveness Of Artificial Neochordae Implantation In Tricuspid Valve Repair, Salih Salihi, H Tarik Kiziltan, Ahmad Huraibat, Askin Ali Korkmaz, Ibrahim Kara, Mustafa Guden

The Texas Heart Institute Journal

Various techniques for treating tricuspid regurgitation have been described; however, because of scarce data about the long-term outcomes of different repairs, the optimal technique has not been established. We evaluated the effectiveness and durability of artificial neochordae implantation in the treatment of tricuspid regurgitation. From 2009 through 2014, 507 patients underwent tricuspid valve repair at our institution. Of those, 48 patients implanted with artificial neochordae were included in our study. The median age of the participants was 62 years (range, 4-77 yr) and 50% were women. Thirty patients (63%) were in New York Heart Association functional class III, and 11 …

An Unusual Case Of Takotsubo Cardiomyopathy In Pheochromocytoma, Paolo Angelini

The Texas Heart Institute Journal

No abstract provided.

Unconventional 2:1 Ventricular Pacing In A Neonate With Congenital Heart Block And Biventricular Noncompaction, Andrew E Schneider, Philip L Wackel

The Texas Heart Institute Journal

Congenital complete heart block with concomitant biventricular noncompaction cardiomyopathy has been reported once previously. Although not universal, when restrictive physiology is present, impaired diastolic filling may pose a distinct challenge to pacing during the neonatal period. We present the case of a neonate with congenital complete heart block and biventricular noncompaction that resulted in severe diastolic dysfunction and atrioventricular dyssynchrony. We intentionally used 2:1 ventricular pacing to provide atrioventricular synchrony with every paced beat, and this resulted in hemodynamic and clinical improvement. This unconventional pacing technique may be beneficial in other neonates who have complete heart block and diastolic dysfunction.

More On Waiting For Test Results: When A Doctor Is The Patient, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Minimally Invasive Endovascular Repair Of Ascending Thoracic Aortic Aneurysm With Use Of Local Anesthesia And Conscious Sedation, Abdelkader Almanfi, Zvonimir Krajcer

The Texas Heart Institute Journal

Ascending thoracic aortic aneurysm (ATAA) is typically treated surgically. No commercially available device has been specifically designed for endovascular ATAA repair, and currently, multiple anatomic and technical challenges affect its feasibility. Previously, such repairs have been performed with the patients under general anesthesia. We describe a novel, minimally invasive approach to endovascular repair of ATAA, involving local anesthesia, conscious sedation, and 24-hour hospitalization. Two consecutive male patients (ages, 79 and 54 yr) who had comorbidities underwent percutaneous transfemoral endovascular ATAA repair with use of commercially available endografts. Patient 1 had a saccular aneurysm, and Patient 2 had a pseudoaneurysm consequent …

Effect Of Percutaneous Suction Thromboembolectomy On Improved Right Ventricular Function, Akbarshakh Akhmerov, Heidi Reich, James Mirocha, Danny Ramzy

The Texas Heart Institute Journal

Venous thromboembolism is a leading cause of cardiovascular death. Historically, surgical intervention has been associated with high morbidity rates. Pharmacologic therapy alone can be inadequate for patients with substantial hemodynamic compromise, so minimally invasive procedures are being developed to reduce clot burden. We describe our initial experience with using the AngioVac system to remove thromboemboli percutaneously. We reviewed all suction thromboembolectomy procedures performed at our institution from March 2013 through August 2015. The main indications for the procedure were failed catheter-directed therapy, contraindication to thrombolysis, bleeding-related complications, and clot-in-transit phenomena. We collected details on patient characteristics, procedural indications, thrombus location, …

Transapical Implantation Of Edwards Sapien Xt Valve To Close A Left Ventricular Outflow Tract Pseudoaneurysm, Jorge Peñalver, Wassim Shatila, Francisco Y Macedo, Guilherme V Silva

The Texas Heart Institute Journal

No abstract provided.

Clinical Evaluation Of Exercise Capacity In Adults With Systemic Right Ventricle, Beata Rog, Kinga Salapa, Magdalena Okolska, Natalia Dluzniewska, Piotr Werynski, Piotr Podolec, Lidia Tomkiewicz-Pajak

The Texas Heart Institute Journal

The right ventricle provides systemic circulation in individuals with congenitally corrected transposition of the great arteries (CCTGA) and in those with complete transposition who have had an atrial switch repair (DTGA). The aim of this study was to evaluate how the systemic right ventricle adapts to increased workload and oxygen demand during exercise. From November 2005 through December 2015, 3,358 adult patients with congenital heart disease were treated at our institution; we identified 48 (26 females, 22 males; median age, 25.4 ± 8.1 yr) who met the study criteria; 37 had DTGA and atrial switch repair, and 11 had CCTGA. …

Chicken-Fried Steak Changed My Outlook On Medicine, Michael J Lehner

The Texas Heart Institute Journal

No abstract provided.

Cardiac Replacement In Our Lifetime, Jack G Copeland

The Texas Heart Institute Journal

No abstract provided.

Waiting For Test Results, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Preventing A Catastrophe: Increasing Awareness Of Loeys-Dietz Syndrome, Bradley S Kane, Kamran Shamsa

The Texas Heart Institute Journal

Loeys-Dietz syndrome is a genetic disorder that predisposes patients to aortic aneurysms. If left untreated, the natural history of the associated aortopathy often culminates in fatal aortic dissection. We describe the case of a 21-year-old man who was diagnosed with Loeys-Dietz syndrome after 2 family members died of aortic dissection. This case highlights the importance of increased physician awareness of this syndrome, which can play a crucial role in preventing premature sudden cardiac death caused by aortic catastrophe.

The Future Of Tissue Engineering In Heart Transplantation, Doris A Taylor

The Texas Heart Institute Journal

No abstract provided.

Role Of Multimodal Cardiac Imaging In Diagnosing A Primary Intimal Sarcoma Of The Left Atrial Appendage, Kara L Raphael, Anthony P Martinez, Stephen D Clements, Ijeoma Isiadinso

The Texas Heart Institute Journal

Primary cardiac tumors are rare, and most are benign. Intimal sarcomas are among the rarest of the malignant cardiac tumors; they are aggressive and associated with a poor prognosis. Whereas transesophageal echocardiography has been instrumental in evaluating cardiac masses, other imaging methods, such as cardiac magnetic resonance, have proved invaluable in accurately characterizing these masses. We present the case of a 49-year-old woman in whom we diagnosed a primary intimal sarcoma of the left atrial appendage, and we discuss the importance of multimodal imaging in the evaluation and diagnosis of cardiac masses.

Penetrating Atherosclerotic Ulcer Of The Ascending Aorta Found Incidentally In A 71-Year-Old Man, Antonino M Grande, Dario Di Perna, Adele Valentini, Eloisa Arbustini

The Texas Heart Institute Journal

No abstract provided.