Diseases Commons^™

External Validation Of The Phoenix Sepsis Score In Children With Suspected Community-Acquired Sepsis, Elliot Long, Meredith Borland, Shane George, Shefali Jani, Eunicia Tan, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Ben Gelbart, Sarah Mcnab, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Charlotte Brad, Amanda Williams, Franz Babl

Department of Medicine Faculty Papers

IMPORTANCE: The novel Phoenix Sepsis Score and sepsis criteria were derived and validated using a multicountry dataset and proposed as a new definition for sepsis in children.

OBJECTIVE: To externally validate the Phoenix Sepsis Score and sepsis criteria in a cohort of children hospitalized with suspected community-acquired sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study used data from the multicenter, multicountry Sepsis Epidemiology in Australian and New Zealand Emergency Departments (SENTINEL) study, collected from 2021 to 2023 and including 90-day follow-up. Children admitted to the hospital through 11 emergency departments in Australia and New Zealand and treated with parenteral antibiotics …

Comparison Between Maia And Mp-3 In Healthy Subjects And Patients With Diabetes, Diabetic Retinopathy, And Age-Related Macular Degeneration, Anna Marmalidou, Haleema Siddiqui, Muhammad Usman Jamil, Kwang Min Woo, Antonio Yaghy, A. Yasin Alibhai, Hiroyuki Takahashi, Stephanie Kaiser, Keith Effert, Peter Zhao, Shilpa Desai, Christopher Robinson, Jay Duker, Nadia Waheed

SKMC Student Presentations and Publications

PURPOSE: The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.

METHODS: This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to …

Epstein-Barr Virus Sequence Variations Among The Understudied Nasopharyngeal Carcinoma Patients Of Diverse Ancestries In Southeast Asia, Hwee Sze Tee, Jingtong Liang, Norazlin Abdul Aziz, Xiang Zhou, Hamidah Akmal Hisham, Ke-En Tan, Yanhong Chen, Zuriani Burhanuddin, Johnny S.H. Kwan, Kwok-Wai Lo, Faridah Hassan, Sha'ariyah Bt Mohd Mokhtar, Alan Soo Beng Khoo, Miao Xu, Yat-Yuen Lim, Lu Ping Tan

Department of Medical Oncology Faculty Papers

Epstein-Barr virus (EBV) is associated with cancers, including lymphomas and nasopharyngeal carcinoma (NPC). To date, risk variants for NPC were mainly identified from Chinese populations, which dominated the world's total number of cases. Although Southeast Asia (SEA) countries have among the world's top yet intriguingly diverse NPC age-standardized incidence rates across subpopulations, data on EBV from SEA remains scarce. In this study, we examined 83 NPC patients of different ancestries for the presence of risk haplotypes associated with the Southern Chinese NPC and generated and analyzed 67 EBV sequences (from tissue, patient-derived xenografts and lymphoblastoid cell lines of 60 NPC …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

A Multicenter Training And Interrater Reliability Study Of The Based Score For Infantile Epileptic Spasms Syndrome, John R Mytinger, Dara V F Albert, Shawn C Aylward, Christopher W Beatty, Sonam Bhalla, Sonal Bhatia, Guy N Brock, Micheal A Ciliberto, Purva R Choudhari, Daniel J Clark, Jennifer Madan Cohen, Theresa M Czech, Megan M Fredwall, Ernesto Gonzalez-Giraldo, Chellamani Harini, Senyene E Hunter, Amanda G Sandoval Karamian, Akshat Katyayan, Isaac Kistler, Neil Kulkarni, Virginia B Liu, Corinne Mccabe, Thomas Murray, Kerri Neville, Shital H Patel, Spriha Pavuluri, Donald J Phillips, Debopam Samanta, Deepa Sirsi, Emily M Spelbrink, Carl E Stafstrom, Maija Steenari, Danielle S Takacs, Tyler Terrill, Linh Tran, Jorge Vidaurre, Daniel W Shrey

Faculty, Staff and Students Publications

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE).

METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 …

An Adaptive Antiretroviral Therapy Adherence Intervention For Youth With Hiv Through Text Message And Cell Phone Support With And Without Incentives: A Sequential Multiple Assignment Randomized Trial (Smart), Marvin E Belzer, Karen Macdonell, Demetria Cain, Samiran Ghosh, Richard Zhao, Julie Mcavoy-Banerjea, Sitaji Gurung, Sylvie Naar

Faculty, Staff and Student Publications

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL < 200 or adherence > 80% after the initial 3 months were rerandomized to usual care …

Temperature-Controlled Radiofrequency Treatment Of The Nasal Valve In Nasal Airway Obstruction Patients With Septal Deviation, Dennis M Tang, Philip G Chen, Arthur W Wu, William C Yao

Faculty, Staff and Student Publications

Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.

Plasma Cell-Rich Lymphoid Neoplasm In An Endocervical Polyp Of The Uterine Cervix In A Perimenopausal 52-Year-Old Woman, Anjali Patel, Jacqueline Haas, Angela Kueck

HCA Healthcare Journal of Medicine

Background

The adaptive immune system consists of T and B lymphocytes, with some B lymphocytes further differentiating into plasma cells that secrete antibodies and make up the humoral immune system. Extramedullary plasmacytoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and plasmablastic lymphoma are all plasma cell-rich lymphoid neoplasms that rarely present in the female genital tract. To date, few case reports of these malignancies arising within the uterine cervix exist.

Case Presentation

This case report describes a 52-year-old perimenopausal woman who presented to her primary obstetrician-gynecologist for an annual exam with the complaint of light spotting following an endometrial ablation that occurred …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev Sen, Omar Alwakaa, Christoph Griessenauer, Pascal Jabbour, Stavropoula Tjoumakaris, Jan-Karl Burkhardt, Robert Starke, Mustafa Baskaya, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng Chen, Spiros Blackburn, Mark Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman Patel, Hugo Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Department of Neurosurgery Faculty Papers

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

Associations Of Long-Term Exposure To Temperature With Coronary Artery Calcification Risk Among Middle-Aged Adults: The Coronary Artery Risk Development In Young Adults (Cardia) Study, Dandan Zhao, Jie Yao, Yuanfei Li, David R Jacobs, Yinan Zheng, Chunyu Liu, Yingbin Fu, Margaret M Deangelis, Donald Lloyd-Jones, Lifang Hou, Kai Zhang

Faculty, Staff and Students Publications

BACKGROUND: The impact of ambient temperature on population health has drawn increasing attention as climate change drives more extreme temperatures globally. However, little research has investigated its connection to subclinical cardiovascular diseases. This study aims to examine the impact of long-term exposure to temperature on coronary artery calcification (CAC) among middle-aged Black and White adults in four U.S. areas with varying climate and weather conditions.

METHODS: This study compiled long-term environmental temperature data and individual coronary artery Agatston score (0 vs. >0) from the Coronary Artery Risk Development in Young Adults study. It employed logistic regression and examined the influences …

Ultrasound-Triggered Release Of Vancomycin From A Novel Spinal Device: Antibiotic Release And Efficacy In Vivo, Lauren J. Delaney, Priscilla Machado, Ji-Bin Liu, Rachel Evans, Asia Winslow, Neil Zhao, Christopher K. Kepler, Rajkishen Narayanan, Teeto Ezeonu, Viren Soni, Gagan Kaushal, Rachel Hilliard, Thomas P. Schaer, Noreen J. Hickok, Flemming Forsberg

Department of Orthopaedic Surgery Faculty Papers

Post-surgical spinal infection occurs in up to 20 % of patients, despite aggressive peri-operative antibiotic treatments. To improve prophylaxis, we have designed and evaluated an ultrasound-activated prophylactic antibiotic release system to combat post-surgical bacterial survival. Polylactic acid (PLA) clips (1 cm³) were 3D-printed with an interior reservoir (0.8 cm³) for carrying drug payload, specifically vancomycin (VAN). Under IACUC approval, clips were surgically implanted into the spines of sheep (n = 9) and swine (n = 2) by removing the spinous process at several levels of the lumbar spine. In the sheep, clips were insonated and the …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi

Faculty, Staff and Student Publications

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.

Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam Jaber, Carin Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal Gandhi, Keith Pereira, Jay Giri, Sameer Khandhar, Khawaja Afzal Ammar, David Lasorda, Brian Stegman, Lucas Busch, David Dexter, Ezana Azene, Nikhil Daga, Fakhir Elmasri, Chandra Kunavarapu, Mark Rea, Joseph Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason Smith, Thomas Tamlyn, Gabriel Hernandez, Parth Rali, Torrey Schmidt, Jeffrey Bruckel, Juan Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian Bergmark, Bhavraj Khalsa, David Zlotnick, Jordan Castle, David O'Connor, C. Michael Gibson

Department of Radiology Faculty Papers

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Infection-Related Hospitalization And Incident Heart Failure: The Atherosclerosis Risk In Communities Study, Rebecca L Molinsky, Amil Shah, Melana Yuzefpolskaya, Bing Yu, Jeffrey R Misialek, Bruno Bohn, David Vock, Richard Maclehose, Barry A Borlaug, Paolo C Colombo, Chiadi E Ndumele, Junichi Ishigami, Kunihiro Matsushita, Pamela L Lutsey, Ryan T Demmer

Faculty, Staff and Student Publications

Background: The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.

Methods and results: We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987-1989). IRH was identified using select International Classification of Diseases (ICD) codes in hospital discharge records and was treated as a time-varying exposure. HF incidence was defined as the first occurrence …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Mid-Life Anti-Inflammatory Metabolites Are Inversely Associated With Long-Term Cardiovascular Disease Events, Anum Saeed, Chris Mckennan, Jiaxuan Duan, Yueh-Ning Yang, Kevin E Kip, David Finegold, Michael Vu, Justin Swanson, Oscar L Lopez, Ann Cohen, Mark Mapstone, Bing Yu, Christie M Ballantyne, Steven E Reis

Faculty, Staff and Student Publications

BACKGROUND: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

METHODS: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.1 ± 7.5 years old, 69.6% female, 43.6% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Logistic regression was used to assess the impact of metabolite levels on ASCVD risk (nonfatal MI, revascularisation, and cardiac mortality). We additionally explored the effect of genetic variants neighbouring ASCVD-related genes …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Characterizing Prodrome (Premonitory Phase) In Migraine: Results From The Prodrome Trial Screening Period, Todd Schwedt, Richard Lipton, Peter Goadsby, Chia-Chun Chiang, Brad Klein, Cory Hussar, Chengcheng Liu, Sung Yun Yu, Michelle Finnegan, Joel Trugman

College of Nursing Faculty Papers & Presentations

BACKGROUND AND OBJECTIVE: Limited data are available describing the frequency, severity, and consistency of prodromal symptoms followed by headache. This analysis of the PRODROME trial screening period characterized prodromal symptoms in people with migraine, including the most common symptoms and their severity, and the frequency and consistency with which prodromal symptoms were followed by headache.

METHODS: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial conducted in the United States that enrolled adults with 2-8 migraine attacks per month who stated they could identify prodromal symptoms that were reliably followed by a headache. The trial included a 60-day screening period …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …

Implementation Of Electronic Triggers To Identify Diagnostic Errors In Emergency Departments, Viralkumar Vaghani, Ashish Gupta, Usman Mir, Li Wei, Daniel R Murphy, Umair Mushtaq, Dean F Sittig, Andrew J Zimolzak, Hardeep Singh

Faculty, Staff and Students Publications

Importance: Missed diagnosis can lead to preventable patient harm.

Objective: To develop and implement a portfolio of electronic triggers (e-triggers) and examine their performance for identifying missed opportunities in diagnosis (MODs) in emergency departments (EDs).

Design, setting, and participants: In this retrospective medical record review study of ED visits at 1321 Veterans Affairs health care sites, rules-based e-triggers were developed and implemented using a national electronic health record repository. These e-triggers targeted 6 high-risk presentations for MODs in treat-and-release ED visits. A high-risk stroke e-trigger was applied to treat-and-release ED visits from January 1, 2016, to December 31, 2020. A …

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Examining Health Insurance And Non-Medical Challenges Among Vietnamese Americans In Texas During The Covid-19 Pandemic, Alexander Le, Saba Siddiqi, Celine Nguyen, Ben King, Paul Gerardo Yeh, Jannette Diep, Lauren Gilbert, Bich-May Nguyen

Faculty, Staff and Student Publications

When COVID-19 data on Asian Americans are available, they are frequently aggregated, concealing community-specific concerns. Consequently, there is limited COVID-19 literature on Vietnamese Americans. In this study, we investigated the association between health insurance coverage and non-medical challenges during the COVID-19 pandemic, in Vietnamese Americans in Texas. The NIH Community Engagement Alliance (CEAL) Common Survey 2 was administered electronically in English and Vietnamese and contained 23 questions about non-medical drivers of health, COVID-19 vaccination, and research participation. Vietnamese American adults in Texas were recruited between September 2021 and March 2022 via partnerships with community organizations. Responses were compared and analyzed …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …