Medical Specialties Commons^™

Deep Image Segmentation For Cardiomyocyte Proliferation, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

No abstract provided.

Impact Of Obesity And Age On Mouse Corneal Innervation At The Epithelial-Stromal Interface, Justin A Courson, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

PURPOSE: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age.

METHODS: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the …

Chlorthalidone Vs Hydrochlorothiazide For Hypertension Treatment After Myocardial Infarction Or Stroke: A Secondary Analysis Of A Randomized Clinical Trial, Areef Ishani, Cynthia Hau, William C Cushman, Sarah M Leatherman, Robert A Lew, Peter A Glassman, Addison A Taylor, Ryan E Ferguson

Faculty, Staff and Students Publications

IMPORTANCE: Patients with prior myocardial infarction (MI) or stroke have a greater risk of recurrent cardiovascular (CV) events.

OBJECTIVE: To evaluate the association of chlorthalidone (CTD) vs hydrochlorothiazide (HCTZ) with CV outcomes and noncancer deaths in participants with and without prior MI or stroke.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of the Diuretic Comparison Project (DCP), a pragmatic randomized clinical trial conducted within 72 participating Veterans Affairs health care systems from June 2016 to June 2021, in which patients aged 65 years or older with hypertension taking HCTZ at baseline were randomized to continue HCTZ or …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Sialic Acid-Siglec-E Interactions Regulate The Response Of Neonatal Macrophages To Group B Streptococcus, Sean J Lund, Pamela G B Del Rosario, Asami Honda, Kaitlin J Caoili, Marten A Hoeksema, Victor Nizet, Kathryn A Patras, Lawrence S Prince

Faculty, Staff and Students Publications

The mammalian Siglec receptor sialoadhesin (Siglec1, CD169) confers innate immunity against the encapsulated pathogen group B Streptococcus (GBS). Newborn lung macrophages have lower expression levels of sialoadhesin at birth compared with the postnatal period, increasing their susceptibility to GBS infection. In this study, we investigate the mechanisms regulating sialoadhesin expression in the newborn mouse lung. In both neonatal and adult mice, GBS lung infection reduced Siglec1 expression, potentially delaying acquisition of immunity in neonates. Suppression of Siglec1 expression required interactions between sialic acid on the GBS capsule and the inhibitory host receptor Siglec-E. The Siglec1 gene contains multiple STAT binding …

Association Of Cardiovascular Health With Subclinical Coronary Atherosclerosis Progression Among Five Racial And Ethnic Groups: The Masala And Mesa Studies, Vardhmaan Jain, Mahmoud Al Rifai, Alka M Kanaya, Nilay S Shah, Sameera A Talegawkar, Salim S Virani, Erin D Michos, Roger S Blumenthal, Jaideep Patel

Faculty, Staff and Students Publications

Background and aims: South Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups.

Methods: We assessed the distribution of CVH metrics (inadequate: score 0-8, average: 9-10, optimal: 11-14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of …

Trends And Updates On The Epidemiology Of Cancer Associated Thrombosis: A Systematic Review, Ang Li, Emily Zhou

Faculty, Staff and Students Publications

Introduction: Cancer associated thrombosis (CAT) is a significant complication for patients with cancer. This review summarizes an updated epidemiology of CAT in the past decade.

Methods: A systematic review was conducted on relevant population cohort studies published 2011-2024.

Results: The 12-month incidence of CAT among patients with unselected cancers is approximately 3-5% (9-fold increase vs. matched non-cancer population); although the risk increases to 6-8% in patients with advanced cancers requiring systemic therapy (20-fold increase vs. matched non-cancer population). Despite improvement in anticoagulation usage and adherence, recurrence risk remains high at 5-8% at 6 months and 7-15% at 12 months. Important …

Emerging Evidence For Glucagon-Like Peptide-1 Agonists In Slowing Chronic Kidney Disease Progression, Michael W Holliday, Livia Frost, Sankar D Navaneethan

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes.

RECENT FINDINGS: Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, …

Angiogenic Gene Therapy For Refractory Angina: Results Of The Exact Phase 2 Trial, Kenta Nakamura, Timothy D Henry, Jay H Traverse, David A Latter, Nahush A Mokadam, Geoffrey A Answini, Adam R Williams, Benjamin C Sun, Christopher R Burke, Faisal G Bakaeen, Marcelo F Dicarli, Bernard R Chaitman, Mark W Peterson, Dawn G Byrnes, E Magnus Ohman, Carl J Pepine, Ronald G Crystal, Todd K Rosengart, Elaine Kowalewski, Gary G Koch, Howard C Dittrich, Thomas J Povsic, Exact Trial Investigators

Faculty, Staff and Students Publications

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery.

Results: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients …

Association Between Gamma Glutamyl Transpeptidase To Hdl-Cholesterol (Ggt/Hdl-C) Ratio And Metabolic Syndrome Resolution After Sleeve Gastrectomy, Melanni L. Lizarbe-Lezama, Jhoel E. Rodriguez-Macedo, Daniel Fernandez-Guzman, Ana L. Alcantara-Diaz, Gustavo Salinas-Sedo, Carlos J. Toro-Huamanchumo

Research outputs 2022 to 2026

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], …

Engineering Small-Molecule And Protein Drugs For Targeting Bone Tumors, Yixian Wang, Chenhang Wang, Meng Xia, Zeru Tian, Joseph Zhou, Julian Meyer Berger, Xiang H-F Zhang, Han Xiao

Faculty, Staff and Students Publications

Bone cancer is common and severe. Both primary (e.g., osteosarcoma, Ewing sarcoma) and secondary (e.g., metastatic) bone cancers lead to significant health problems and death. Currently, treatments such as chemotherapy, hormone therapy, and radiation therapy are used to treat bone cancer, but they often only shrink or slow tumor growth and do not eliminate cancer completely. The bone microenvironment contributes unique signals that influence cancer growth, immunogenicity, and metastasis. Traditional cancer therapies have limited effectiveness due to off-target effects and poor distribution on bones. As a result, therapies with improved specificity and efficacy for treating bone tumors are highly needed. …

Total Aortic Arch Replacement Using A Frozen Elephant Trunk Device: Results Of A 1-Year Us Multicenter Trial, Joseph S Coselli, Eric E Roselli, Ourania Preventza, S Chris Malaisrie, Allan Stewart, Paul Stelzer, Hiroo Takayama, Edward P Chen, Anthony L Estrera, Thomas G Gleason, Michael P Fischbein, Leonard N Girardi, Himanshu J Patel, Joseph E Bavaria, Scott A Lemaire

Faculty, Staff and Students Publications

Objective: In this prospective US investigational device exemption trial, we assessed the safety and 1-year clinical outcomes of the Thoraflex Hybrid device (Terumo Aortic) for the frozen elephant trunk technique to repair the ascending aorta, aortic arch, and descending thoracic aorta.

Methods: For the trial, which involved 12 US sites, 65 patients without rupture were recruited into the primary study group, and 9 patients were recruited into the rupture group. All patients underwent open surgical repair of the ascending aorta, aortic arch, and descending thoracic aorta in cases of aneurysm and/or dissection. The primary end point was freedom from major …

Association Of Body Iron Stores And Anemia In A Ghanaian Type-2 Diabetes Mellitus Population: A Multicentered Cross-Sectional Study, Wina I.O. Boadu, William K.B.A. Owiredu, Emmanuel Timmy Donkoh, Kwame O. Boadu, Afia A. Kwayie, Joseph Frimpong, Enoch O. Anto, Christian Obirikorang, Emmanuel E. Korsah, Ezekiel Ansah, Michael Nyantakyi, Stephen Opoku, Ebenezer Senu, Elizabeth Aboagye

Research outputs 2022 to 2026

Background and Aims: Anemia has been a common comorbidity in most chronic diseases, but has not been well monitored in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the prevalence of anemia and its nexus with iron stores among T2DM patients in health facilities in the Ashanti Region of Ghana. Methods: This multicenter cross-sectional study recruited 213 T2DM out-patients attending the diabetic clinics at the Kumasi South Hospital and St. Michaels Hospital, Jachie Pramso, Ghana, for routine check-ups. Self-reported questionnaires were used to collect sociodemographic, lifestyle, and clinical data from study participants. Blood samples were collected to …

Altered Myocardial Lipid Regulation In Junctophilin-2-Associated Familial Cardiomyopathies, Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens

Faculty, Staff and Students Publications

Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and …

Predictors And Impact Of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation, Harveen K Lamba, Mary Kim, Meng Li, Andrew B Civitello, Ajith P Nair, Leo Simpson, J Patrick Herlihy, O H Frazier, Joseph G Rogers, Gabriel Loor, Kenneth K Liao, Alexis E Shafii, Subhasis Chatterjee

Faculty, Staff and Students Publications

BACKGROUND: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known.

OBJECTIVES: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation.

METHODS: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours …

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …

Tenapanor As Therapy For Hyperphosphatemia In Maintenance Dialysis Patients: Results From The Optimize Study, Stuart M Sprague, Daniel E Weiner, David P Tietjen, Pablo E Pergola, Steven Fishbane, Geoffrey A Block, Arnold L Silva, Stephen Z Fadem, Robert I Lynn, George Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M Spiegel, David P Rosenbaum

Faculty, Staff and Students Publications

KEY POINTS: Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.

METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline

RESULTS: By part A end point, 34.4% (

CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P …

Use Of Topical Methylene Blue To Image Nuclear Morphometry With A Low-Cost Scanning Darkfield Microendoscope, Huayu Hou, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Sharmila Anandasabapathy, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

SIGNIFICANCE: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for

AIM: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract.

APPROACH: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and …

The Employment Of Resuscitative Endovascular Balloon Occlusion Of The Aorta In Deployed Settings, Branson D. Taheri, Andrew D. Fisher, Ian F. Eisenhauer, Michael D. April, Julie A. Rizzo, Sundeep S. Guliani, Kathleen M. Flarity, Michael Cripps, Vikhyat S. Bebarta, Max V. Wohlauer, Steven G. Schauer

Faculty Publications

Excerpt: We identified 17 cases of REBOA placed in combat settings from 2017 to 2019. The majority of these were placed in the operating room (76%) and in civilian patients (70%).

Consensus Guidelines For The Diagnosis And Management Of Succinic Semialdehyde Dehydrogenase Deficiency, Itay Tokatly Latzer, Mariarita Bertoldi, Nenad Blau, Melissa L Dibacco, Sarah H Elsea, Àngels García-Cazorla, K Michael Gibson, Andrea L Gropman, Ellen Hanson, Carolyn Hoffman, Kathrin Jeltsch, Natalia Juliá-Palacios, Ina Knerr, Henry H C Lee, Patrizia Malaspina, Alice Mcconnell, Thomas Opladen, Mari Oppebøen, Alexander Rotenberg, Mark Walterfang, Lee Wang-Tso, Ron A Wevers, Jean-Baptiste Roullet, Phillip L Pearl

Faculty, Staff and Students Publications

Succinic semialdehyde dehydrogenase deficiency (SSADHD) (OMIM #271980) is a rare autosomal recessive metabolic disorder caused by pathogenic variants of ALDH5A1. Deficiency of SSADH results in accumulation of γ-aminobutyric acid (GABA) and other GABA-related metabolites. The clinical phenotype of SSADHD includes a broad spectrum of non-pathognomonic symptoms such as cognitive disabilities, communication and language deficits, movement disorders, epilepsy, sleep disturbances, attention problems, anxiety, and obsessive-compulsive traits. Current treatment options for SSADHD remain supportive, but there are ongoing attempts to develop targeted genetic therapies. This study aimed to create consensus guidelines for the diagnosis and management of SSADHD. Thirty relevant statements were …

Rna Sequencing For Solid Tumor Fusion Gene Detection: Proficiency Testing Practice And Performance Comparison, Julia A Bridge, Kevin C Halling, Joel T Moncur, Rhona J Souers, Meera R Hameed, Helen Fernandes, Angshumoy Roy, Lea Surrey, Laura J Tafe, Patricia Vasalos, Dolores H Lopez-Terrada

Faculty, Staff and Students Publications

Context: Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays.

Objective: To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B).

Design: CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed …

Association Of Minor Electrocardiographic (Ecg) Abnormalities With Epilepsy Duration In Children: A Manifestation Of The Epileptic Heart?, Brittnie Bartlett-Lee, Leslie Dervan, Christina Miyake, R Scott Watson, See Wai Chan, Anne E Anderson, Yi-Chen Lai

Faculty, Staff and Students Publications

Purpose: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG).

Methods: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling. …

Exposure To 4,4′-Dde In Visceral Adipose Tissue And Weight Loss In Adolescents From The Teen-Labs Cohort, Bruna Rubbo, Zhenjiang Li, Phum Tachachartvanich, Brittney O Baumert, Hongxu Wang, Shudi Pan, Sarah Rock, Justin R Ryder, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Michele A La Merrill, Douglas I Walker, David V Conti, Rob Mcconnell, Sandrah P Eckel, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes.

Methods: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight …

Clofarabine Monotherapy In Aggressive, Relapsed And Refractory Langerhans Cell Histiocytosis, Deevyashali Parekh, Howard Lin, Akanksha Batajoo, Erin Peckham-Gregory, Vivekanudeep Karri, Whitney Stanton, Brooks Scull, Ryan Fleishmann, Nader El-Mallawany, Olive S Eckstein, Zachary D Prudowsky, Nitya Gulati, Jennifer E Agrusa, Asra Z Ahmed, Roland Chu, Matthew S Dietz, Stanton C Goldman, Michael D Hogarty, Hamayun Imran, Stefanos Intzes, Jenny M Kim, Lisa M Kopp, Carolyn Fein Levy, Philip Neff, Pallavi M Pillai, Bryan A Sisk, Deborah E Schiff, Angela D Trobaugh-Lotrario, Kelly Walkovich, Kenneth L Mcclain, Carl E Allen

Faculty, Staff and Students Publications

Over 50% of patients with systemic LCH are not cured with front-line therapies and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort including heavily pretreated patients with systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood correlated with positive clinical responses. Prospective multi-center trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Longitudinal Natural History Studies Based On Real-World Data In Rare Diseases: Opportunity And A Novel Approach, Laura Ann Adang, Anjana Sevagamoorthy, Omar Sherbini, Jamie L Fraser, Joshua L Bonkowsky, Francesco Gavazzi, Russel D'Aiello, Nicholson B Modesti, Emily Yu, Sylvia Mutua, Emma Kotes, Justine Shults, Ariel Vincent, Lisa T Emrick, Stephanie Keller, Keith P Van Haren, Sarah Woidill, Isabella Barcelos, Amy Pizzino, Johanna L Schmidt, Florian Eichler, Ali Fatemi, Adeline Vanderver

Faculty, Staff and Students Publications

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records.

Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture …

The Evidence Is Mounting: Insurance Coverage Disruptions Lead To Worse Outcomes Among Children Diagnosed With Cancer, Philip J Lupo, Christina L Magyar

Faculty, Staff and Students Publications

No abstract provided.

Validation Of Single-Nucleotide Mosaic Variants Through Droplet Digital Pcr, Christopher M Grochowski, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The detection, validation, and subsequent interpretation of potentially mosaic single-nucleotide variants (SNV) within next-generation sequencing data remains a challenge in both research and clinical laboratory settings. The ability to identify mosaic variants in high genome coverage sequencing data at levels of 1% or lower underscores the necessity for developing guidelines and best practices to verify these variants orthogonally. Droplet digital PCR (ddPCR) has proven to be a powerful and precise method that allows for the determination of low-level variant fractions within a given sample. Herein we describe two precise ddPCR methods using either a fluorescent TaqMan hydrolysis probe approach or …

Social Determinants Of Health And Risk Of Stillbirth In The United States, April Adams, Deepa Dongarwar, Lena Shay, Mariana Baroni, Eunique Williams, Priscilla Ehieze, Rhanna Wilson, Alexia Awoseyi, Hamisu M Salihu

Faculty, Staff and Students Publications

Objective: Our aim was to evaluate the impact of social determinants of health (SDoH) risk factors on stillbirth among pregnancy-related hospitalizations in the United States.

Study design: We conducted a cross-sectional analysis of delivery-related hospital discharges using annualized data (2016-2017) from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. The International Classification of Diseases, 10th Revision ICD-10-CM codes were used to select women with singleton stillbirth. Z-codes were utilized to identify SDoH risk factors and their subtypes. The association between SDoH risk factors and stillbirth was assessed using survey logistic regression models.

Results: We analyzed 8,148,646 hospitalizations, out of …

Systematic Evaluation Of Machine Learning-Enhanced Trifocal Iol Power Selection For Axial Myopia Cataract Patients, Danmin Cao, Min Hu, Danlin Zhi, Jianheng Liang, Qian Tan, Qiong Lei, Maoyan Li, Hao Cheng, Li Wang, Weiwei Dai

Faculty, Staff and Students Publications

Purpose: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs.

Design: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied.

Methods: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven …

Pragmatic Strategies To Address Health Disparities Along The Continuum Of Care In Chronic Liver Disease, Mayur Brahmania, Shari Rogal, Marina Serper, Arpan Patel, David Goldberg, Amit Mathur, Julius Wilder, Jennifer Vittorio, Andrew Yeoman, Nicole E Rich, Mariana Lazo, Ani Kardashian, Sumeet Asrani, Ashley Spann, Nneka Ufere, Manisha Verma, Elizabeth Verna, Dinee Simpson, Jesse D Schold, Russell Rosenblatt, Lisa Mcelroy, Sharad I Wadhwani, Tzu-Hao Lee, Alexandra T Strauss, Raymond T Chung, Ignacio Aiza, Rotonya Carr, Jin Mo Yang, Carla Brady, Brett E Fortune

Faculty, Staff and Students Publications

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.