Diseases Commons^™

Prediction Of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial (18)F-Fdg Pet/Ct, Michael Chuong

Michael Chuong

No abstract provided.

Proton Pump Inhibitors Increase The Severity Of Hepatic Encephalopathy In Cirrhotic Patients, Matthew J. Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Jomol Mathew, Yurima Guilarte-Walker, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.

AIM: To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE …

Robustness Of A Newly Proposed Risk Schema For Lymphatic Dissemination In Endometrioid Endometrial Cancer, Danielle M. Greer, Jessica J.F. Kram, Callie M. Cox Bauer, Scott A. Kamelle

Aurora Ob/Gyn Faculty

Background: Surgical management for endometrioid endometrial cancer (EEC) includes complete lymph node dissection for all patients at risk of lymphatic dissemination. The standard risk schema, defined by Mayo Clinic, identifies low-risk patients as those with grade 1/2 EEC, myometrial invasion (MI) ≤ 50%, and tumor diameter (TD) ≤ 2 cm. We recently proposed (and published) a risk schema containing modified forms of grade, MI and TD that suggests a significant decrease in false-negative rate and need for lymphadenectomy in low-risk women.

Purpose: Evaluate robustness of our proposed schema for lymphatic dissemination risk stratification in a subsequent EEC patient cohort.

Methods: …

Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard

Gyongyi Szabo

Introduction: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI.

Methods: A single center, retrospective chart review, …

Changes In Anticoagulant Utilization Among United States Nursing Home Residents With Atrial Fibrillation From 2011 To 2016, Matthew Alcusky, David D. Mcmanus, Anne L. Hume, Marc Fisher, Jennifer Tjia, Kate L. Lapane

Jennifer Tjia

Background: Nursing home residents with atrial fibrillation are at high risk for ischemic stroke and bleeding events. The most recent national estimate (2004) indicated less than one third of this high-risk population was anticoagulated. Whether direct-acting oral anticoagulant ( DOAC ) use has disseminated into nursing homes and increased anticoagulant use is unknown.

Methods and Results: A repeated cross-sectional design was used to estimate the point prevalence of oral anticoagulant use on July 1 and December 31 of calendar years 2011 to 2016 among Medicare fee-for-service beneficiaries with atrial fibrillation residing in long-stay nursing homes. Nursing home residence was determined …

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

Minesh Mehta

No abstract provided.

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Komal Sodhi

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Mechanisms Of Left Ventricular Thrombus Formation In Heart Failure With Reduced Ejection Fraction: Novel Insights From Two-Dimensional Speckle Tracking Echocardiography, Dhruv Chawla, Tracy Hammonds, Tadele Mengesha, Matt Umland, Khawaja Afzal Ammar, Vinay Thohan

Aurora Heart Failure / Transplant Faculty

Background: Patients suffering from heart failure with reduced ejection fraction (HFrEF) are at increased risk for left ventricular (LV) thrombus and subsequent thromboembolism, yet anticoagulation is not routinely recommended for left ventricular ejection fraction (LVEF) alone. We sought to determine the role of two-dimensional speckle tracking echocardiography (2D-STE) to quantify regional changes in cardiac function associated with LV thrombus, which may prospectively guide anticoagulation.

Purpose: Help enable cardiovascular clinicians to use 2D-STE to evaluate regional strain patterns among patients with HFrEF with and without LV thrombus. Our results suggest that statistically lower regional longitudinal strain patterns in a well-matched cohort …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Aurora Heart Failure / Transplant Faculty

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Limiting Antibiotic Use In Acute Sinusitis: Partly A Matter Of Vocabulary?, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In his issue introduction, the editor-in-chief of Journal of Patient-Centered Research and Reviews comments on an included article that describes the successful use of an electronic medical record best practice alert to reduce the rate of antibiotic prescription for acute sinusitis. Various methods previously tried to improve antibiotic stewardship in this illness are briefly reviewed. Borrowing on the model of acute bronchitis, it is suggested that a change in conveyed diagnostic vocabulary to “sinus cold” when describing acute sinusitis may help limit antibiotics for this predominantly viral infection.

Use Of Urine Antigen Testing For Blastomyces In An Integrated Health System, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Purpose: Blastomycosis, an endemic fungal infection, mimics many other diseases. We explored the use of Blastomyces urine antigen (BuAg), reportedly the most sensitive noninvasive test, in clinical practice and compared it to other noninvasive tests.

Methods: A total of 836 BuAg tests performed on unique patients (first test only) at one large integrated health system from June 2013 to May 2016 were retrospectively reviewed to examine test characteristics and demographic features. Of these, 100 cases from 2015, a year containing a large local blastomycosis outbreak, were randomly selected for detailed analysis.

Results: Demographics for the BuAg-tested population: mean age 54.9 …

Assessment Of Chronic Disease To Determine Appropriateness Of Implantable Cardioverter-Defibrillator Therapy, Bilal M. Omery, Maharaj Singh, Randy S. Turkel, Robyn Shearer, Arshad Jahangir, M. Eyman Mortada, Jasbir S. Sra, Indrajit Choudhuri

Indrajit Choudhuri, MD

Background: Implantable cardioverter-defibrillator (ICD) therapy is considered appropriate when a patient is felt to have a reasonable expectation of 1-year survival. Chronic diseases have been estimated to be associated with greater than 10% annual mortality and may reduce benefits of ICD therapy. Frailty has been estimated to be associated with greater than 20% annual mortality and has been suggested to contraindicate ICD therapy.

Purpose: Determine a risk score that may identify patients in whom ICD implantation may not be appropriate.

Methods: Patients who received an ICD for primary and secondary prevention from 2008 through 2013 at the Aurora Health Care …

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create …

Clinical Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Surgery In High Surgical Risk Patients With Left Main Or Three-Vessel Coronary Artery Disease, Tonga Nfor, Kambiz Shetabi, Wael Hassan, Quinta Nfor, Jayant Khitha, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband

Aurora Cardiology Fellows

Purpose Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass graft surgery (CABG) in patients with unprotected left main or three-vessel coronary artery disease (LM-3VD) have excluded patients at high surgical risk. We compared clinical outcomes after PCI with drug-eluting stents to CABG in high surgical risk patients with LM-3VD. Methods Patients with symptomatic LM-3VD who had Society of Thoracic Surgeons (STS)-predicted operative mortality >5% and were undergoing either PCI with drug-eluting stents or CABG at a tertiary care center from January 2009 to December 2010 were enrolled in this nonrandomized prospective study. Results Mean STS score was …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Nasir Sulemanjee, MD, FACC

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Zero-Fluoroscopy Cavotricuspid Isthmus Ablation Using Carto Mapping System As Sole Guiding Method, Wassim Ballany, Indrajit Choudhuri, Mohamed Djelmami-Hani, Ryan L. Cooley

Aurora Electrophysiology Fellows

Background: Catheter ablation of the cavotricuspid isthmus (CTI) is traditionally performed using fluoroscopy and electroanatomical mapping systems. Zero-fluoroscopy approaches have recently been studied, mostly using the EnSite^® mapping system (St. Jude Medical Inc., St. Paul, MN). We studied the feasibility and efficacy of zero-fluoroscopic mapping and ablation of the CTI using the Carto^® 3 system (Biosense Webster Inc., South Diamond Bar, CA).

Purpose: To evaluate the efficacy and safety of a zero-fluoroscopic approach to CTI ablation.

Methods: We included 9 patients with typical atrial flutter for whom mapping and ablation of the CTI was done using Carto mapping …

The Crux Of The Heart –– The Closest Approach Of The Right Atrium To The Left Ventricle, Lynn Erickson, David Krum, Hannah Samuel, Anwer Dhala, Jasbir Sra

Jasbir Sra, MD, FACC, Program Director

Background: Accessory pathways, the source of atrioventricular reentry tachycardia, occasionally connect the left ventricle to the right atrium. This is possible because, in some patients, a portion of the right atrium abuts the left ventricle on the posterior wall of the heart, near the mid-coronary sinus. This anatomic region is known as the “crux” of the heart. These accessory pathways can be difficult to ablate because of the unusual and unexpected substrate. While the presence of these accessory pathways is described in the literature, the prevalence of the underlying anatomic substrate is not currently known.

Purpose: To measure the closest …

Predicting Outcomes In Patients With Atrial Fibrillation And Acute Mesenteric Ischemia, Sanjay Bhandari, Geetanjali Dang, Muhammad Shahreyar, Ahmad Hanif, Vijayadershan Muppidi, Atul Bhatia, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir

Jasbir Sra, MD, FACC, Program Director

Purpose Outcomes in patients with atrial fibrillation who develop acute mesenteric ischemia, and the impact of anticoagulation on complications, are not defined. Methods Patients admitted with acute mesenteric ischemia in the National Inpatient Sample from 2007, with and without atrial fibrillation, were compared for in-hospital outcomes using multivariate regression, and the impact of prior anticoagulation determined. Results Of 48,872 patients with acute mesenteric ischemia, 8,306 had atrial fibrillation, with 680 patients also on anticoagulation. Atrial fibrillation patients were more likely to be older and have hypertension, heart failure, or chronic lung or renal disease. After adjusting for potential confounders, atrial …

Atrial Fibrillation And Stroke In Elderly Patients, Geetanjali Dang, Imaan Jahangir, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir

Jasbir Sra, MD, FACC, Program Director

The increasing prevalence of stroke, with an estimated annual cost of $71.5 billion, has made it a major health problem that increases disability and death, particularly in patients with atrial fibrillation. Although advanced age and atrial fibrillation are recognized as strong risk factors for stroke, the basis for this susceptibility are not well defined. Aging or associated diseases are accompanied by changes in rheostatic, humoral, metabolic and hemodynamic factors that may contribute more to stroke predisposition than rhythm abnormality alone. Several thromboembolism-predisposing clinical characteristics and serum biomarkers with prognostic significance have been identified in patients with atrial fibrillation. Although anticoagulation …

Lead Burden As A Factor For Higher Complication Rate In Patients With Implantable Cardiac Devices, Christopher Kolibash, Naoyo Mori, Jasbir Sra, Masood Akhtar, M. Eyman Mortada

Mohammad Mortada, MD, FACC, FHRS

Purpose Lead revisions have increased over the last decade. Patients who do not undergo lead extraction face an increased lead burden. Consequences of increased lead burden have not been fully defined. We sought to characterize the complication rate and outcomes in patients with sterile redundant leads. Methods We retrospectively reviewed 242 consecutive patients [mean age 74 ± 12 years; 66.9% male] who underwent lead revision that resulted in an abandoned lead from January 2005 to June 2010. Patients were placed in a cohort based on number of leads after last recorded procedure (Group A: ≤2 [n=58]; Group B: 3-4 [n=168]; …

Predicting Outcomes In Patients With Atrial Fibrillation And Acute Mesenteric Ischemia, Sanjay Bhandari, Geetanjali Dang, Muhammad Shahreyar, Ahmad Hanif, Vijayadershan Muppidi, Atul Bhatia, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir

Atul Bhatia, MD, FACC

Purpose Outcomes in patients with atrial fibrillation who develop acute mesenteric ischemia, and the impact of anticoagulation on complications, are not defined. Methods Patients admitted with acute mesenteric ischemia in the National Inpatient Sample from 2007, with and without atrial fibrillation, were compared for in-hospital outcomes using multivariate regression, and the impact of prior anticoagulation determined. Results Of 48,872 patients with acute mesenteric ischemia, 8,306 had atrial fibrillation, with 680 patients also on anticoagulation. Atrial fibrillation patients were more likely to be older and have hypertension, heart failure, or chronic lung or renal disease. After adjusting for potential confounders, atrial …

Therapeutic Raavrh10 Mediated Sod1 Silencing In Adult Sod1(G93a) Mice And Nonhuman Primates, Florie Borel, Gwladys Gernoux, Brynn Cardozo, Jake P. Metterville, Gabriela Toro Cabrera, Lina Song, Qin Su, Guang Ping Gao, Mai K. Elmallah, Robert H. Brown Jr., Christian Mueller

Christian Mueller

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; survival in ALS is typically 3-5 years. No treatment extends patient survival by more than three months. Approximately 20% of familial ALS and 1-3% of sporadic ALS patients carry a mutation in the gene encoding superoxide dismutase 1 (SOD1). In a transgenic ALS mouse model expressing the mutant SOD1(G93A) protein, silencing the SOD1 gene prolongs survival. One study reports a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice; this was achieved with a short hairpin RNA, a silencing molecule that has raised multiple safety concerns, and …

Sustained Expression With Partial Correction Of Neutrophil Defects 5 Years After Intramuscular Raav1 Gene Therapy For Alpha-1 Antitrypsin Deficiency, Terence R. Flotte, Christian Mueller, Gwladys Gernoux, Alisha Gruntman, Jeffrey D. Chulay, David R. Knop, Noel G. Mcelvaney, Martha Campbell-Thompson, James M. Wilson

Christian Mueller

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in …

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

Indrajit Choudhuri, MD

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 …