Digital Commons Network^™

The Safety Of Combined Triple Drug Therapy With Ivermectin, Diethylcarbamazine And Albendazole In The Neglected Tropical Diseases Co-Endemic Setting Of Fiji: A Cluster Randomised Trial, Myra Hardy, Josaia Samuela, Mike Kama, Meciusela Tuicakau, Lucia Romani, Margot J. Whitfeld, Christopher L. King, Gary J. Weil, Anneke C. Grobler, Leanne J. Robinson, John M. Kaldor, Andrew C. Steer

Open Access Publications

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days …

Disease-Modifying Therapy Adherence And Associated Factors In A National Sample Of Medicare Patients With Multiple Sclerosis, Pengxiang Li, Vrushabh P Ladage, Joseph Berger, Salim Chahin, Mehul Jhaveri, Caroline Geremakis, Jalpa A Doshi

Open Access Publications

OBJECTIVES: Disease-modifying therapies (DMTs) reduce relapse rates and disability progression for relapsing multiple sclerosis (MS). Although 25% to 30% of all US patients with MS are Medicare beneficiaries, limited information exists on this population. This is the first study using national Medicare data to (1) describe characteristics of patients with MS using DMTs, (2) estimate adherence to DMTs over a 1-year and 3-year follow-up, and (3) examine factors associated with DMT adherence.

METHODS: This retrospective claims analysis used 2011-2014 100% Medicare files. Monthly adherence to MS DMTs was defined as the proportion of days covered ≥0.80 with any DMT in …

Decision-Making Based On 3d Printed Models In Laparoscopic Liver Resections With Intraoperative Ultrasound: A Prospective Observational Study, Jan Witowski, Andrzej Budzyński, Anna Grochowska, David H Ballard, Piotr Major, Mateusz Rubinkiewicz, Adriana Złahoda-Huzior, Tadeusz J Popiela, Mateusz Wierdak, Michał Pędziwiatr

Open Access Publications

OBJECTIVES: The aim of this study was to evaluate impact of 3D printed models on decision-making in context of laparoscopic liver resections (LLR) performed with intraoperative ultrasound (IOUS) guidance.

METHODS: Nineteen patients with liver malignances (74% were colorectal cancer metastases) were prospectively qualified for LLR or radiofrequency ablation in a single center from April 2017 to December 2018. Models were 3DP in all cases based on CT and facilitated optical visualization of tumors' relationships with portal and hepatic veins. Planned surgical extent and its changes were tracked after CT analysis and 3D model inspection, as well as intraoperatively using IOUS. …

Coaction Between Physical Activity And Fruit And Vegetable Intake In Racially Diverse, Obese Adults, Natalia I Heredia, Maria E Fernandez, Alexandra E Van Den Berg, Casey P Durand, Harold W Kohl, Belinda M Reininger, Kevin O Hwang, Lorna H Mcneill

Faculty, Staff and Student Publications

PURPOSE: There is minimal understanding of the potential for coaction, defined as action on one behavior increasing the likelihood of taking action on another behavior, between physical activity (PA) and fruit and vegetable (FV) intake. The purpose of this study was to assess the bidirectional coaction between FV intake and PA, as well as self-efficacy for these behaviors, in a racially diverse sample of obese adults.

DESIGN: This is a secondary analysis using data collected from the Path to Health study, a randomized controlled trial. ClinicalTrials.gov Identifier: NCT03674229.

SAMPLE: Obese adults who completed baseline and 6-month follow-up assessments.

MEASURES: For …

Fibrin Clots Maintain The Viability And Proliferative Capacity Of Human Mesenchymal Stem Cells: An In Vitro Study, Ryan J Warth, Paul G Shupe, Xueqin Gao, Mohammad Syed, Walter R Lowe, Johnny Huard, Christopher D Harner

Faculty, Staff and Student Publications

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive …

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …

Orthostatic Hypotension, Cardiovascular Outcomes, And Adverse Events: Results From Sprint, Stephen P Juraschek, Addison A Taylor, Jackson T Wright, Gregory W Evans, Edgar R Miller, Timothy B Plante, William C Cushman, Tanya R Gure, William E Haley, Imran Moinuddin, John Nord, Suzanne Oparil, Carolyn Pedley, Christianne L Roumie, Jeff Whittle, Alan Wiggers, Ciarán Finucane, Rose Anne Kenny, Lawrence J Appel, Raymond R Townsend

Faculty, Staff and Students Publications

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial of adults, age ≥50years at high risk for cardiovascular disease (CVD) with a seated systolic BP (SBP) of 130–180 mmHg and a standing SBP ≥110 mmHg. Participants were randomized to a SBP treatment goal of either <120 mmHg or <140 mmHg. OH was defined as a drop in SBP≥20 or diastolic BP ≥10 mmHg one minute after standing from a seated position. We used Cox models to examine the association of OH with CVD or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1,170 (5.7%) instances of OH among those assigned a standard BP goal, and 1,057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of CVD events (primary outcome: HR 1.06; 95%CI: 0.78,1.44). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (HR 1.77; 1.11,2.82) and bradycardia (HR 1.94; 1.19,3.15), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of CVD events and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

Second-Line Lenvatinib In Patients With Recurrent Endometrial Cancer, Ignace Vergote, Matthew A Powell, Michael G Teneriello, David S Miller, Agustin A Garcia, Olga N Mikheeva, Mariusz Bidzinski, Cristina Ligia Cebotaru, Corina E Dutcus, Min Ren, Tadashi Kadowaki, Yasuhiro Funahashi, Richard T Penson

Open Access Publications

OBJECTIVE: This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as second-line therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes.

METHODS: An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after …

Temporal Trends And Geographic Variations In Mortality Rates From Prescription Opioids: Lessons From Florida And West Virginia, Sarah A Palumbo, Charles H Hennekens, Janet D Robishaw, Robert S Levine

Faculty, Staff and Students Publications

OBJECTIVES: To explore temporal trends and geographic variations in mortality from prescription opioids from 1999 to 2016.

METHODS: Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death files were used to calculate age-adjusted rates and 95% confidence intervals (CIs) and create spatial cluster maps.

RESULTS: From 1999 to 2016, counties in West Virginia experienced the highest overall mortality rates in the United States from prescription opioids. Specifically, from 1999 to 2004, the highest rate in West Virginia of 24.87/100,000 (95% CI 17.84-33.73) was the fourth highest in the United States. From 2005 to …

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …

Staged Laser Interstitial Thermal Therapy (Litt) Treatments To Left Insular Low-Grade Glioma, Daniel M. Hafez, Caroline Liekweg, Eric C. Leuthardt

2020-Current year OA Pubs

BACKGROUND AND IMPORTANCE: Low-grade insular gliomas remain challenging tumors for aggressive resection because of the numerous functional and vascular structures surrounding them. Because of the potential morbidities associated with open surgical resection, less invasive techniques may confer a more optimal balance between cytoreduction and surgical complications. For this reason, we evaluated the use of laser interstitial thermal therapy (LITT) for resection of a dominant hemisphere oligodendroglioma World Health Organization (WHO) grade II in a 68-yr-old patient by use of multiple staged surgeries for its resection.

CLINICAL PRESENTATION: Patient KK was a 68-yr-old female who was found to have a large, …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias: Executive Summary, Edmond M Cronin, Phillip Cuculich, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Correction Of Respiratory Artifacts In Mri Head Motion Estimates, Damien A. Fair, Abraham Z. Snyder, Andrew N. Van, Jonathan M. Koller, Amy E. Mirro, Jacqueline M Hampton, Babatunde Adeyemo, Timothy O. Laumann, Deanna J. Greene, Deann M. Barch, Steven E. Petersen, Nico U. F. Dosenbach, Et Al.

2020-Current year OA Pubs

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated …

Polr1b And Neural Crest Cell Anomalies In Treacher Collins Syndrome Type 4, Elodie Sanchez, Tomi L Toler, Walton Nephi, Marcia Willing, Et Al.

2020-Current year OA Pubs

PURPOSE: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2-1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation. To date, three genes have been identified: TCOF1, POLR1C, and POLR1D. Despite a large number of patients with a molecular diagnosis, some remain without a known genetic anomaly.

METHODS: We performed exome sequencing for four individuals with TCS but who were negative for pathogenic variants in the known causative genes. The effect of the pathogenic variants was investigated in zebrafish.

RESULTS: …

Mail-Back Envelopes For Retrieval Of Opioids After Pediatric Surgery, Adam C Adler, Ammar N Yamani, Caitlin D Sutton, Danielle M Guffey, Arvind Chandrakantan

Faculty, Staff and Students Publications

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery.

METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well …

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

Targeted Therapy For Advanced Salivary Gland Carcinoma Based On Molecular Profiling: Results From Mypathway, A Phase Iia Multiple Basket Study, R Kurzrock, D W Bowles, H Kang, F Meric-Bernstam, J Hainsworth, D R Spigel, R Bose, H Burris, C J Sweeney, M S Beattie, S Blotner, K Schulze, V Cuchelkar, C Swanton

2020-Current year OA Pubs

BACKGROUND: Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics.

PATIENTS AND METHODS: MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab [high tumor mutational burden (TMB)]. The primary endpoint is the objective response rate …

Characterization Of Urinary Concentrations Of Heavy Metals Among Socioeconomically Disadvantaged Black Pregnant Women, Inkyu Han, Kristina W Whitworth, Xueying Zhang, Masoud Afshar, Pamela D Berens, Elaine Symanski

Faculty, Staff and Student Publications

The objective of this study was to characterize exposures to metals using biological samples collected on socioeconomically disadvantaged black pregnant women. We obtained 131 anonymous urine samples provided by black pregnant women visiting a Medicaid-serving prenatal clinic in Houston, TX, from March 27, 2017 to April 11, 2017. We analyzed urine samples for 15 metals including cadmium (Cd), arsenic (As), lead (Pb), and nickel (Ni) and for creatinine and cotinine. We found that median concentrations of zinc (Zn), selenium (Se), and aluminum (Al) among black pregnant women in this study were 1.5 to 3 times higher than levels reported among …

How To Stop The Bleed: First Care Provider Model For Developing Public Trauma Response Beyond Basic Hemorrhage Control, Joshua P Bobko, Dylan J Badin, Leila Danishgar, Kate Bayhan, Kevin J Thompson, William J Harris, R. Todd Baldridge, Gerald R Fortuna

Open Access Publications

INTRODUCTION: Since 2013, the First Care Provider (FCP) model has successfully educated the non-medical population on how to recognize life-threatening injuries and perform interventions recommended by the Committee for Tactical Emergency Casualty Care (C-TECC) and the Hartford Consensus in the disaster setting. Recent programs, such as the federal "Stop The Bleed" campaign, have placed the emphasis of public training on hemorrhage control. However, recent attacks demonstrate that access to wounded, recognition of injury, and rapid evacuation are equally as important as hemorrhage control in minimizing mortality. To date, no training programs have produced a validated study with regard to training …

Simulation-Based Mastery Learning Compared To Standard Education For Discussing Diagnostic Uncertainty With Patients In The Emergency Department: A Randomized Controlled Trial., Danielle M. Mccarthy, Rhea E. Powell, Kenzie A. Cameron, David H. Salzman, Dimitrios Papanagnou, Amanda Doty, Benjamin E. Leiby, Katherine Piserchia, Matthew R. Klein, Xiao C. Zhang, William C. Mcgaghie, Kristin L. Rising

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications.

METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to …

Development Of An Abbreviated Symptom Score For The Neonatal Abstinence Syndrome., I. Chervoneva, S. C. Adeniyi-Jones, F. Blanco, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument.

STUDY DESIGN: Retrospective cohort.

RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element …

Immune Checkpoint Modulation Enhances Hiv-1 Antibody Induction., Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G. Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O. Saunders, Rafi Ahmed, John R. Mascola, Garnett Kelsoe, Frederick W. Alt, Barton F. Haynes

Manuscripts, Articles, Book Chapters and Other Papers

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

Proof-Of-Concept Study Of The Efficacy Of A Microbiota-Directed Complementary Food Formulation (Mdcf) For Treating Moderate Acute Malnutrition, Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed

Open Access Publications

BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy …

Outcomes Of Inflammatory Bowel Disease In Patients With Eosinophil-Predominant Colonic Inflammation, Tarik Alhmoud, Anas Gremida, Diego Colom Steele, Imaneh Fallahi, Wael Tuqan, Nina Nandy, Mahmoud Ismail, Barakat Aburajab Altamimi, Meng-Jun Xiong, Audra Kerwin, David Martin

Pathology Research and Scholarship

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear.

METHODS: This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded.

RESULTS: 142 treatment-naïve IBD patients were included. Mean age was 39 …

Treatment De-Escalation For Hpv-Associated Oropharyngeal Squamous Cell Carcinoma With Radiotherapy Vs. Trans-Oral Surgery (Orator2): Study Protocol For A Randomized Phase Ii Trial., Anthony C Nichols, Pencilla Lang, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Kevin Fung, John R De Almeida, Andrew Bayley, David P Goldstein, Antoine Eskander, Zain Husain, Houda Bahig, Apostolos Christopoulous, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle Macneil, Adrian Mendez, Eric Winquist, Nancy Read, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Martin Corsten, Murali Rajaraman, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Shamir Chandarana, Robyn Banerjee, Joseph Dort, T Wayne Matthews, Robert Hart, Paul Kerr, Samuel Dowthwaite, Michael Gupta, Han Zhang, Jim Wright, Christina Parker, Bret Wehrli, Keith Kwan, Julie Theurer, David A Palma

Paediatrics Publications

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. …

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014., Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

Dynamic Imaging Of Ldh Inhibition In Tumors Reveals Rapid In Vivo Metabolic Rewiring And Vulnerability To Combination Therapy, Nobu Oshima, Ryo Ishida, Shun Kishimoto, Kristin Beebe, Jeffrey R. Brender, Kazutoshi Yamamoto, Daniel Urban, Ganesha Rai, Michelle S. Johnson, Gloria Benavides, Giuseppe L. Squadrito, Dan Crooks, Joseph Jackson, Abhinav Joshi, Bryan T. Mott, Jonathan H. Shrimp, Michael A. Moses, Min-Jung Lee, Akira Yuno, Tobie D. Lee, Xin Hu, Tamara Anderson, Donna Kusewitt, Helen H. Hathaway, Ajit Jadhav, Didier Picard, Jane B. Trepel, James B. Mitchell, Gordon M. Stott, William Moore, Anton Simeonov, Larry A. Sklar, Jeffrey P Norenberg, W Marston Linehan, David J. Maloney, Chi V. Dang, Alex G. Waterson, Matthew Hall, Victor M. Darley-Usmar, Murali C. Krishna, Leonard M. Neckers

Pathology Research and Scholarship

The reliance of many cancers on aerobic glycolysis has stimulated efforts to develop lactate dehydrogenase (LDH) inhibitors. However, despite significant efforts, LDH inhibitors (LDHi) with sufficient specificity and in vivo activity to determine whether LDH is a feasible drug target are lacking. We describe an LDHi with potent, on-target, in vivo activity. Using hyperpolarized magnetic resonance spectroscopic imaging (HP-MRSI), we demonstrate in vivo LDH inhibition in two glycolytic cancer models, MIA PaCa-2 and HT29, and we correlate depth and duration of LDH inhibition with direct anti-tumor activity. HP-MRSI also reveals a metabolic rewiring that occurs in vivo within 30 min …

Global Longitudinal Strain And Cardiac Events In Patients With Immune Checkpoint Inhibitor-Related Myocarditis., Magid Awadalla, Syed S Mahmood, John D Groarke, Malek Z O Hassan, Anju Nohria, Adam Rokicki, Sean P Murphy, Nathaniel D Mercaldo, Lili Zhang, Daniel A Zlotoff, Kerry L Reynolds, Raza M Alvi, Dahlia Banerji, Shiying Liu, Lucie M Heinzerling, Maeve Jones-O'Connor, Rula B Bakar, Justine V Cohen, Michael C Kirchberger, Ryan J Sullivan, Dipti Gupta, Connor P Mulligan, Sachin P Shah, Sarju Ganatra, Muhammad A. Rizvi Md, Gagan Sahni, Carlo G Tocchetti, Donald P Lawrence, Michael Mahmoudi, Richard B Devereux, Brian J Forrestal, Anant Mandawat, Alexander R Lyon, Carol L Chen, Ana Barac, Judy Hung, Paaladinesh Thavendiranathan, Michael H Picard, Franck Thuny, Stephane Ederhy, Michael G Fradley, Tomas G Neilan

Department of Medicine

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.

OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.

METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not …

The Impact Of An Undergraduate Biology Class On Donor Recruitment At A Hospital-Based Blood Donor Center, Alexis R. Peedin, Yara A. Park, Marshall A. Mazepa, Thomas Neish, Jay S. Raval, R Chad Siniard

Pathology Research and Scholarship

OBJECTIVES: A biology class, BIOL 294H, taught undergraduates about platelet donation while partnering with the University of North Carolina's (UNC's) hospital-based Blood Donation Center to recruit apheresis platelet donors. We identified our platelet donors' demographics and learned how BIOL 294H affected recruitment.

METHODS: Every platelet donor presenting to the UNC Blood Donation Center from February 7, 2017, to March 10, 2017, was asked to complete an electronic 10-question survey.

RESULTS: A total of 159 unique donors completed the survey; 64% were female and 75% were between ages 18 and 25 years. Overall, 70% were UNC undergraduate students. Over half (56%) …