Digital Commons Network^™

A Retrospective Analysis Of Clinical Use Of Alirocumab In Lipoprotein Apheresis Patients, Anne C Goldberg, Richard L Dunbar, Linda Hemphill, Stephan P Babirak, Gerald Wilson, Michael Wooten, Mohamed Iydroose, Kelley Dacus, Heather Minchew, Julie-Ann Dutton, Patrick M Moriarty

2020-Current year OA Pubs

BACKGROUND: The previously published ODYSSEY ESCAPE trial demonstrated a significant reduction in the use of lipoprotein apheresis for heterozygous familial hypercholesterolemia (HeFH) patients when placed on alirocumab 150 mg every 2 weeks. In patients with HeFH who have consistently elevated levels of low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy, current lipid guidelines recommend apheresis. Although apheresis reduces LDL-C levels by 50%-75%, it must be repeated, as frequently as every 1-2 weeks.

OBJECTIVE: To assess clinical experience with apheresis and alirocumab for patients in a real-world practice setting.

METHODS: This retrospective review included patients from 5 apheresis centers who …

Variable Expression Of Msh6 In Endometrial Carcinomas With Intact Mismatch Repair And With Mlh1 Loss Due To Mlh1 Methylation, Nidhi Tandon, Courtney Hudgens, Bryan Fellman, Michael T Tetzlaff, Russell R Broaddus

Faculty, Staff and Student Publications

Immunohistochemistry for mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 is an effective screen to detect individuals at risk for Lynch syndrome. College of American Pathologists guidelines stipulate that protein expression should be reported as present versus absent, as most patients with germline mutations in a mismatch repair gene have complete loss of protein expression in tumor cells. A similar approach is employed to screen for cancer patients eligible for immune checkpoint blockade. This "all or none" interpretive approach ignores substantial evidence that mismatch repair may be more finely regulated by other mechanisms. We have observed clinically that MSH6 expression …

The Impact Of Chronic Kidney Disease On Outcomes Following Peripheral Vascular Intervention., Dennis I Narcisse, Elizabeth Hope Weissler, Jennifer A Rymer, Ehrin J Armstrong, Eric A Secemsky, William A Gray, Jihad A Mustapha, George L Adams, Gary M Ansel, Manesh R Patel, William Schuyler Jones

Heart and Vascular Articles

BACKGROUND: Patients with chronic kidney disease (CKD) have worsened clinical outcomes following percutaneous coronary intervention; however, limited evidence exists in patients undergoing peripheral vascular intervention (PVI).

PURPOSE: We aimed to assess the effect of CKD on outcomes following PVI for symptomatic peripheral artery disease.

METHODS: Using patients from the LIBERTY 360 study, we compared the rates of 30 day and 1 year major adverse vascular events (MAVE), a composite of all-cause mortality, major amputation, and target vessel/lesion revascularization, between patients with and without CKD (estimated glomular filtration rate less than 60) following PVI. Multivariable adjustment was performed to assess for …

Paclitaxel Exposure: Long-Term Safety And Effectiveness Of A Drug-Coated Balloon For Claudication In Pooled Randomized Trials., Peter A Schneider, Marianne Brodmann, Laura Mauri, John Laird, Yoshimitsu Soga, Antonio Micari, Gary Ansel, Mehdi H Shishehbor, Prakash Krishnan, Qi Gao, Kenneth Ouriel, Thomas Zeller

Heart and Vascular Articles

BACKGROUND: Paclitaxel drug-coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow-up have raised uncertainty regarding long-term mortality.

OBJECTIVES: To evaluate the effect of paclitaxel exposure on the long-term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials.

METHODS: The IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long-term safety, sites were requested to obtain vital status follow-up. In the pooled, …

Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute

Faculty, Staff and Students Publications

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …

Pr Depression With Multilead St Elevation And St Depression In Avr By Left Circumflex Artery Occlusion: How To Differentiate From Acute Pericarditis, Zhong-Qun Zhan, Kjell Nikus, Yochai Birnbaum

Faculty, Staff and Students Publications

PR-segment depression with multilead ST-segment elevation and ST-segment depression in lead aVR are classic ECG manifestation of acute pericarditis. We present a patient, where the etiology of these ECG features was acute ST-elevation myocardial infarction due to left circumflex artery occlusion. To avoid misdiagnosis, unnecessary examinations, and inappropriate therapeutic decisions, the possibility of ST-segment elevation myocardial infarction should be kept in mind even when ECG changes typical for pericarditis are encountered in chest pain patients. Findings of QRS widening and QT interval shortening in leads with ST-segment elevation could help to differentiate acute ST-segment elevation myocardial infarction from acute pericarditis.

Cardiovascular Disease Risk Assessment In Patients With Familial Mediterranean Fever Related Renal Amyloidosis., Micol Romano, David Piskin, Roberta A Berard, Bradley C Jackson, Cengizhan Acikel, Juan J Carrero, Helen J Lachmann, Mahmut I Yilmaz, Erkan Demirkaya

Paediatrics Publications

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and …

Association Of Patient-Centered Medical Home Designation And Quality Indicators Within Hrsa-Funded Community Health Center Delivery Sites, Nathaniel Bell, Rebecca Wilkerson, Kathy Mayfield-Smith, Ana Lòpez-De Fede

Faculty Publications

BACKGROUND: Patient-Centered Medical Home (PCMH) adoption is an important strategy to help improve primary care quality within Health Resources and Service Administration (HRSA) community health centers (CHC), but evidence of its effect thus far remains mixed. A limitation of previous evaluations has been the inability to account for the proportion of CHC delivery sites that are designated medical homes.

METHODS: Retrospective cross-sectional study using HRSA Uniform Data System (UDS) and certification files from the National Committee for Quality Assurance (NCQA) and the Joint Commission (JC). Datasets were linked through geocoding and an approximate string-matching algorithm. Predicted probability scores were …

Association Of Visceral Adipose Tissue And Subclinical Atherosclerosis In Us-Born Mexican Americans But Not First Generation Immigrants, Clarence Gill, Miryoung Lee, Kristina P Vatcheva, Nahid Rianon, Beverly Smulevitz, David D Mcpherson, Joseph B Mccormick, Susan P Fisher-Hoch, Susan T Laing

Faculty, Staff and Student Publications

Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of …

Relationships Between Accelerometry And General Compensatory Movements Of The Upper Limb After Stroke, Jessica Barth, Joeseph W Klaesner, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Standardized assessments are used in rehabilitation clinics after stroke to measure restoration versus compensatory movements of the upper limb. Accelerometry is an emerging tool that can bridge the gap between in- and out-of-clinic assessments of the upper limb, but is limited in that it currently does not capture the quality of a person's movement, an important concept to assess compensation versus restoration. The purpose of this analysis was to characterize how accelerometer variables may reflect upper limb compensatory movement patterns after stroke.

METHODS: This study was a secondary analysis of an existing data set from a Phase II, single-blind, …

Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.

METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive …

Outcomes Of Venous End-To-Side Microvascular Anastomoses Of The Head And Neck., Matthew Stewart, Perry Hammond, Ishani Khatiwala, Brian Swendseid, Farshid Taghizadeh, Daniel Petrisor, Tingting Zhan, Richard Goldman, Adam Luginbuhl, Ryan Heffelfinger, Larissa Sweeny, Mark K Wax, Joseph M. Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: The literature on outcomes of end-to-side (ETS) anastomoses for microvascular reconstruction of the head and neck is limited. This series reviews ETS in free tissue transfer (FTT) across multiple institutions to better understand their usage and associated outcomes.

STUDY DESIGN: Retrospective review of 2482 consecutive patients across three tertiary institutions.

METHODS: Adult patients (> 18) who received a FTT from 2006 to 2019 were included.

RESULTS: Two hundred and twenty-one FTT were identified as requiring at least one ETS anastomosis. These ETS cases had a failure rate of 11.2% in comparison to 3.8% in a cohort of end-to-end (ETE) …

Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis

Articles, Abstracts, and Reports

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities …

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway.

METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.

RESULTS: NAb titers in …

Outcomes And Management Approaches Of Resuscitative Endovascular Balloon Occlusion Of The Aorta Based On The Income Of Countries, Ramiro Manzano-Nunez, David Mcgreevy, Claudia P. Orlas, Alberto F. Garciá, Tal M. Hörer, Joseph Dubose, Carlos A. Ordoñez, Aast-Aorta Investigators And The Abotrauma Registry Group

Department of Surgery Faculty Publications

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries' income based on the World Bank Country and Lending Groups. Methods: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and …

Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton

Faculty, Staff and Students Publications

Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …

Redefining Cardiac Biomarkers In Predicting Mortality Of Inpatients With Covid-19, Juan-Juan Qin, Xu Cheng, Feng Zhou, Fang Lei, Gauri Akolkar, Jingjing Cai, Xiao-Jing Zhang, Alice Blet, Jing Xie, Peng Zhang, Ye-Mao Liu, Zizhen Huang, Ling-Ping Zhao, Lijin Lin, Meng Xia, Ming-Ming Chen, Xiaohui Song, Liangjie Bai, Ze Chen, Xingyuan Zhang, Da Xiang, Jing Chen, Qingbo Xu, Xin-Liang Ma, Rhian M Touyz, Chen Gao, Haitao Wang, Liming Liu, Weiming Mao, Pengcheng Luo, Youqin Yan, Ping Ye, Manhua Chen, Guohua Chen, Lihua Zhu, Zhi-Gang She, Xiaodong Huang, Yufeng Yuan, Bing-Hong Zhang, Yibin Wang, Peter P Liu, Hongliang Li

Department of Emergency Medicine Faculty Papers

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Trem2 Activation On Microglia Promotes Myelin Debris Clearance And Remyelination In A Model Of Multiple Sclerosis, Francesca Cignarella, Fabia Filipello, Bryan Bollman, Claudia Cantoni, Alberto Locca, Robert Mikesell, Melissa Manis, Adiljan Ibrahim, Li Deng, Bruno A Benitez, Carlos Cruchaga, Danilo Licastro, Kathie Mihindukulasuriya, Oscar Harari, Michael Buckland, David M Holtzman, Arnon Rosenthal, Tina Schwabe, Ilaria Tassi, Laura Piccio

2020-Current year OA Pubs

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for the clearance of myelin debris in areas of demyelination, a key step to allow remyelination. TREM2 is expressed by microglia and promotes microglial survival, proliferation, and phagocytic activity. Herein we demonstrate that TREM2 was highly expressed on myelin-laden phagocytes in active demyelinating lesions in the CNS of subjects with MS. In gene expression studies, macrophages from subjects with TREM2 genetic deficiency displayed a defect in phagocytic pathways. Treatment with a new TREM2 agonistic antibody promoted the …

Mepivacaine Versus Bupivacaine Spinal Anesthesia For Early Postoperative Ambulation., Eric S. Schwenk, Vincent P. Kasper, Jordan D. Smoker, Andrew M. Mendelson, Mathew S. Austin, Scot A. Brown, William J. Hozack, Alexa J. Cohen, Jonathan J. Li, Christopher S. Wahal, Jaime L. Baratta, Marc Torjman, Alyson C. Nemeth, Eric E. Czerwinski

Department of Anesthesiology Faculty Papers

BACKGROUND: Early ambulation after total hip arthroplasty predicts early discharge. Spinal anesthesia is preferred by many practices but can delay ambulation, especially with bupivacaine. Mepivacaine, an intermediate-acting local anesthetic, could enable earlier ambulation than bupivacaine. This study was designed to test the hypothesis that patients who received mepivacaine would ambulate earlier than those who received hyperbaric or isobaric bupivacaine for primary total hip arthroplasty.

METHODS: This randomized controlled trial included American Society of Anesthesiologists Physical Status I to III patients undergoing primary total hip arthroplasty. The patients were randomized 1:1:1 to 52.5 mg of mepivacaine, 11.25 mg of hyperbaric bupivacaine, …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee

2020-Current year OA Pubs

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) …

Comprehensive Pulmonary Safety Review Of Inhaled Technosphere® Insulin In Patients With Diabetes Mellitus, Janet B Mcgill, Anne Peters, John B Buse, Susanne Steiner, Tiffany Tran, Frank M Pompilio, David M Kendall

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Technosphere

METHODS: Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.

RESULTS: Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across …

Oral Leukoplakia And Risk Of Progression To Oral Cancer: A Population-Based Cohort Study, Anil K Chaturvedi, Natalia Udaltsova, Eric A Engels, Jed A Katzel, Elizabeth L Yanik, Hormuzd A Katki, Mark W Lingen, Michael J Silverberg

2020-Current year OA Pubs

BACKGROUND: The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.

METHODS: We conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of …

Genetic Variant Effects On Gene Expression In Human Pancreatic Islets And Their Implications For T2d., Ana Viñuela, Arushi Varshney, Martijn Van De Bunt, Rashmi B Prasad, Olof Asplund, Amanda Bennett, Michael Boehnke, Andrew A Brown, Michael R Erdos, João Fadista, Ola Hansson, Gad Hatem, Cédric Howald, Apoorva K Iyengar, Paul Johnson, Ulrika Krus, Patrick E Macdonald, Anubha Mahajan, Jocelyn E Manning Fox, Narisu Narisu, Vibe Nylander, Peter Orchard, Nikolay Oskolkov, Nikolaos I Panousis, Anthony Payne, Michael L. Stitzel, Swarooparani Vadlamudi, Ryan Welch, Francis S Collins, Karen L Mohlke, Anna L Gloyn, Laura J Scott, Emmanouil T Dermitzakis, Leif Groop, Stephen C J Parker, Mark I Mccarthy

Faculty Research 2020

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in …

Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging For Detection Of Coronary Artery Disease, Andrew E Arai, Pamela K Woodard, Et Al.

2020-Current year OA Pubs

BACKGROUND: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies.

OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging.

METHODS: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant …

Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev

Faculty, Staff and Students Publications

RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca

CONCLUSIONS: Preexisting Ca

Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn

Pathology Research and Scholarship

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …

Population-Level Covid-19 Mortality Risk For Non-Elderly Individuals Overall And For Non-Elderly Individuals Without Underlying Diseases In Pandemic Epicenters, John P.A. Ioannidis, Cathrine Axfors, Despina G. Contopoulos-Ioannidis

All publications

Objective: To provide estimates of the relative rate of COVID-19 death in people < 65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic.

Eligible data: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age < 65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age

Main outcome measures: Proportion of COVID-19 deaths in people < 65 years old; relative mortality rate of COVID-19 death in people < 65 versus ≥ 65 years old; absolute risk of COVID-19 death in people < 65 and in those ≥ 80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle.

Results: Individuals with age < 65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People < 65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥ 65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people < 65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥ 80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people < 65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People < 65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico.

Conclusions: People < 65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people < 65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy., Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Neuroscience Articles

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …