Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

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 …

Disaggregating The Relative Influence Of Genetic, Environmental And Individual Factors On Lcl And Hdl Cholesterols And Bmi For A Sample Of African American (Aa) Mothers And Daughters, C. Jayne Brahler, Jewel Harden, Michelle Mchone, Matthew Soules, Eric Evans, Ann Alyanak, Fred Diakpieng, Paul M. Vanderburgh

Paul M. Vanderburgh

There are many reports about the associations between blood lipids, body mass index (BMI) and dietary cholesterol intakes both within the individual and between related individuals. The purpose of this descriptive research project was to investigate the relationships between LDL and HDL cholesterols, body mass index and dietary cholesterol intakes for a sample of African American (AA) mothers and their daughters and to attempt to separate the contribution of genetic versus environmental factors. Mother and daughter participants (n =42 and 66, respectively) were 12-14-hours fasted when blood samples were drawn, heights and weights measured, and 24 hour food recalls completed.

Real-World Relevance Of Manual Electrocardiography Qt Interval Measurement, Satish Velagapudi, Zahra Nur Khaled, Bilal Omery, Firas Zahwe, Michael Anigbogu, Sarah Zukkoor, Indrajit Choudhuri

Aurora Cardiology Fellows

Background: Electrocardiography (ECG) QT interval (QTI) prolongation independently predicts sudden death. Hospitalized patients are commonly exposed to multiple QT-prolonging drugs, and manual measurement of ECG QTI based on identifying the intersection of isoelectricity with the tangent to the terminal phase T-wave slope (QTTTT) is advocated due to inaccuracies in automated detection algorithms that may imprecisely identify QT duration.

Purpose: We evaluated the performance of QTTTT compared to a standard automated (12SL, GE Healthcare) method (QT-12SL).

Methods: Consecutively obtained ECGs of 250 hospitalized patients were reviewed. The QTI in leads II, aVR, V5 and V6 determined by QT-12SL and QTTTT were …

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 …

Words Do Matter: A Systematic Review On How Different Terminology For The Same Condition Influences Management Preferences, Brooke Nickel, Alexandra Barratt, Tessa Copp, Ray Moynihan, Kirsten Mccaffery

Ray Moynihan

OBJECTIVES: Changing terminology for low-risk, screen-detected conditions has now been recommended by several expert groups in order to prevent overdiagnosis and reduce the associated harms of overtreatment. However, the effect of terminology on patients' preferences for management is not well understood. This review aims to synthesise existing studies on terminology and its impact on management decision making. DESIGN: Systematic review. METHODS: Studies were included that compared two or more terminologies to describe the same condition and measured the effect on treatment or management preferences and/or choices. Studies were identified via database searches from inception to April 2017, and from reference …

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 …

Mhealth Games As Rewards: Incentive Or Distraction?, Kevin Gary, Ryan Stoll, Pooja Rallabhandi, Mandar Patwardhan, Derek Hamel, Ashish Amresh, Armando Pina, Kevin Cleary, Zenaide Quezado

Ashish Amresh

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 …

Enhancing Informative Frame Filtering By Water And Bubble Detection In Colonoscopy Videos, Ashok Dahal, Junghwan Oh, Wallapak Tavanapong, Johnny S. Wong, Piet C. De Groen

Johnny Wong

Colonoscopy has contributed to a marked decline in the number of colorectal cancer related deaths. However, recent data suggest that there is a significant (4-12%) miss-rate for the detection of even large polyps and cancers. To address this, we have been investigating an ‘automated feedback system’ which informs the endoscopist of possible sub-optimal inspection during colonoscopy. A fundamental step of this system is to distinguish non-informative frames from informative ones. Existing methods for this cannot classify water/bubble frames as non-informative even though they do not carry any useful visual information of the colon mucosa. In this paper, we propose a …

Cable Footprint History: Spatio-Temporal Technique For Instrument Detection In Gastrointestinal Endoscopic Procedures, Chuanhai Zhang, Wallapak Tavanapong, Johnny S. Wong, Piet C. De Groen, Junghwan Oh

Johnny Wong

We propose a new fast spatio-temporal technique that detects an operation scene---a video segment corresponding to a single purpose diagnosis action or a single purpose therapeutic action. The technique utilizes (1) color contrast of the cable region and the background, (2) the new area-based coordinate system to compute spatial features, and (3) the history of locations of detected cables of the instrument in a video to discard false regions. The proposed technique and software are useful for (1) automatic documentation of diagnostic or therapeutic operations at the end of the procedure, (2) a second review for causes of complications due …

Recombinant Aav Serotype And Capsid Mutant Comparison For Pulmonary Gene Transfer Of Alpha-1-Antitrypsin Using Invasive And Noninvasive Delivery, Rejean Liqun Wang, Thomas J. Mclaughlin, Travis Cossette, Qiushi Tang, Kevin Foust, Martha Campbell-Thompson, Ashley Martino, Pedro Cruz, Scott Loiler, Christian Mueller, Terence R. Flotte

Christian Mueller

Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 1010 vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar …

Aspira: Employing A Serious Game In An Mhealth App To Improve Asthma Outcomes, Jamie Thomson, Chris Hass, Ivor Horn, Elizabeth Kleine, Stephanie Mitchell, Kevin Gary, Ishrat Ahmed, Derek Hamel, Ashish Amresh

Ashish Amresh

Obat Gatal Kutil Kelamin, Datha Denature

Nama Obat Antibiotik Sipilis Herbl De Nature Indonesia

Complexity And Chaos In Surgical Start Times, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In discussing an article investigating the causes for delay of first-case operating room start times included in this issue of the Journal of Patient-Centered Research and Reviews, the editor uses elements of complexity science and chaos theory to explain that such stubborn problems rarely stem from one of a few isolated causes. Taking a whole systems approach that utilizes flexibility, cross training, enhanced communication, common sense and perhaps mathematical models is suggested to effect positive change.

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]; …

Using Raman Spectroscopy To Improve Hyperpolarized Noble Gas Production For Clinical Lung Imaging Techniques, Jonathan R. Birchall, Nicholas Whiting, Jason G. Skinner, Michael J. Barlow, Boyd M. Goodson

Nicholas Whiting