Medical Specialties Commons^™

New Records Of Ornithodoros Turicata (Ixodida: Argasidae) In Rural And Urban Sites In The Mexican States Of Aguascalientes And Zacatecas Indicate The Potential For Tick-Borne Relapsing Fever, Edwin Vázquez-Guerrero, José Luis González-Quiroz, María Lilia Domínguez-López, Alexander R Kneubehl, Aparna Krishnavajhala, Michael W Curtis, Alejandro Ponce-Mendoza, Paulina Estrada-De Los Santos, Job E Lopez, J Antonio Ibarra

Faculty, Staff and Students Publications

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. …

Assessing The Severity Of Cervical Dystonia: Ask The Doctor Or Ask The Patient?, Adam C Cotton, Laura Scorr, William Mcdonald, Cynthia Comella, Joel S Perlmutter, Christopher G Goetz, Joseph Jankovic, Laura Marsh, Stewart Factor, H A Jinnah

Faculty, Staff and Students Publications

BACKGROUND: Assessing disease severity can be performed using either clinician-rated scales (CRS) or patient-rated outcome (PRO) tools. These two measures frequently demonstrate poor correlations.

OBJECTIVES: To determine if the correlation between a CRS and PRO for motor features of cervical dystonia (CD) improves by accounting for non-motor features.

METHODS: Subjects with CD (N = 209) were evaluated using a CRS (Toronto Western Spasmodic Torticollis Rating Scale, TWSTRS) and a PRO (Cervical Dystonia Impact Profile, CDIP-58).

RESULTS: Linear regression revealed a weak correlation between the two measures, even when considering only the motor subscales of each. The strength of this relationship …

Robot-Assisted Resection Of Tricuspid Valve Papillary Fibroelastoma, Nancy Wang, Zachary Gray, Joseph G Rogers, Kenneth K Liao

Faculty, Staff and Students Publications

We report 3 cases of papillary fibroelastoma of the tricuspid valve. Two of them manifested with atypical symptoms of chest pressure and chest pain. Robot-assisted resection was performed to remove the mass while preserving the native valve. All patients recovered well. The 2 symptomatic patients experienced complete symptom resolution. We demonstrate the safety and feasibility of robotic resection in treating tricuspid valve papillary fibroelastoma.

Cardiometabolic Predictors Of High-Risk Ccta Phenotype In A Diverse Patient Population, Toshiki Kuno, Javier Arce, Michael Fattouh, Sharmila Sarkar, John P Skendelas, Jonathan Daich, Aldo L Schenone, Lili Zhang, Carlos J Rodriguez, Salim S Virani, Piotr J Slomka, Leslee J Shaw, Eric E Williamson, Daniel S Berman, Mario J Garcia, Damini Dey, Leandro Slipczuk

Faculty, Staff and Students Publications

Introduction: Low-attenuation non-calcified plaque (LAP) burden and vascular inflammation by pericoronary adipose tissue (PCAT) measured from coronary CT angiography (CCTA) have shown to be predictors of cardiovascular outcomes. We aimed to investigate the relationships of cardiometabolic risk factors including lipoprotein(a) and epicardial adipose tissue (EAT) with CCTA high-risk imaging biomarkers, LAP and vascular inflammation.

Methods: The patient population consisted of consecutive patients who underwent CCTA for stable chest pain and had a complete cardiometabolic panel including lipoprotein(a). Plaque, PCAT and EAT were measured from CT using semiautomated software. Elevated LAP burden and PCAT attenuation were defined as ≥4% and ≥70.5 …

Studying Ultra-Rare Variants In Stx1a Uncovers A Novel Neurodevelopmental Disorder, Esmeralda Villavicencio Gonzalez, Ryan S Dhindsa

Faculty, Staff and Students Publications

No abstract provided.

Characterizing Control Of Memory Cd8 T Cell Differentiation By Btb-Zf Transcription Factor Zbtb20, Nicholas K Preiss, Yasmin Kamal, Owen M Wilkins, Chenyang Li, Fred W Kolling, Heidi W Trask, Young-Kwang Usherwood, Chao Cheng, Hildreth R Frost, Edward J Usherwood

Faculty, Staff and Students Publications

Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory …

Children’S Oncology Group’S 2023 Blueprint For Research: Non-Hodgkin Lymphoma, Nader Kim El-Mallawany, Sarah Alexander, Mark Fluchel, Robert J Hayashi, Eric J Lowe, Lisa Giulino-Roth, Birte Wistinghausen, Michelle Hermiston, Carl E Allen

Faculty, Staff and Students Publications

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. …

Examining Whether Genetic Variants Moderate The Skeletal Effects Of Selective Serotonin Reuptake Inhibitors In Older Adolescents And Young Adults, Ifeoma Ezenwabachili, Emira Deumic Shultz, James A Mills, Vicki Ellingrod, Chadi A Calarge

Faculty, Staff and Students Publications

Objective: To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Methods: Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin …

Implantable Penile Prosthesis For Erectile Dysfunction: Insurance Coverage In The United States, Mohit Khera, Joshua P Langston, Matthew E Pollard, Denise Asafu-Adjei, Natalie C Edwards, Krista D Nitschelm, Mital Patel, Samir K Bhattacharyya

Faculty, Staff and Students Publications

Introduction: A manufacturer's benefit verification database was evaluated to ascertain United States health plan insurance coverage for implantable penile prostheses for erectile dysfunction.

Methods: All-payer and employer-sponsored health plan benefit verification databases were queried to determine implantable penile prosthesis approval status. For the all-payer analysis, data by payer were available and presented for 2019-2021 to assess approval status varied by payer and over time. For the employer-sponsored health plan analysis, data by payer were available from 2018-2021.

Results: Benefit verification records for the all-payer database were available for 3,167 patients in 2019, 3,016 in 2020, and 2,837 in 2021. Insurance …

The Novel Salt-M Score Predicts 1-Year Post-Transplant Mortality In Patients With Severe Acute-On-Chronic Liver Failure, Ruben Hernaez, Constantine J Karvellas, Yan Liu, Sophie-Caroline Sacleux, Saro Khemichian, Lance L Stein, Kirti Shetty, Christina C Lindenmeyer, Justin R Boike, Douglas A Simonetto, Robert S Rahimi, Prasun K Jalal, Manhal Izzy, Michael S Kriss, Gene Y Im, Ming V Lin, Janice H Jou, Brett E Fortune, George Cholankeril, Alexander Kuo, Nadim Mahmud, Fasiha Kanwal, Faouzi Saliba, Vinay Sundaram, Thierry Artzner, Rajiv Jalan, Multi-Organ Dysfunction And Evaluation For Liver Transplantation (Model) Consortium

Faculty, Staff and Students Publications

Background & aims: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS).

Methods: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up …

Managing The Symptom Burden Associated With Maintenance Dialysis: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Rajnish Mehrotra, Sara N Davison, Ken Farrington, Jennifer E Flythe, Marjorie Foo, Magdalena Madero, Rachael L Morton, Yusuke Tsukamoto, Mark L Unruh, Michael Cheung, Michel Jadoul, Wolfgang C Winkelmayer, Edwina A Brown, Conference Participants

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney …

Global Sumoylation In Mouse Oocytes Maintains Oocyte Identity And Regulates Chromatin Remodeling And Transcriptional Silencing At The End Of Folliculogenesis, Shawn M Briley, Avery A Ahmed, Tessa E Steenwinkel, Peixin Jiang, Sean M Hartig, Karen Schindler, Stephanie A Pangas

Faculty, Staff and Students Publications

Meiotically competent oocytes in mammals undergo cyclic development during folliculogenesis. Oocytes within ovarian follicles are transcriptionally active, producing and storing transcripts required for oocyte growth, somatic cell communication and early embryogenesis. Transcription ceases as oocytes transition from growth to maturation and does not resume until zygotic genome activation. Although SUMOylation, a post-translational modification, plays multifaceted roles in transcriptional regulation, its involvement during oocyte development remains poorly understood. In this study, we generated an oocyte-specific knockout of Ube2i, encoding the SUMO E2 enzyme UBE2I, using Zp3-cre+ to determine how loss of oocyte SUMOylation during folliculogenesis affects oocyte development. Ube2i Zp3-cre+ female …

Revision Tracheotomy Complicated By History Of Follicular B-Cell Lymphoma, Sarah Ustrell, Jordan K Simmons, Garrett Henkle, Adam R Szymanowski

Faculty, Staff and Students Publications

This case report presents a 65-year-old woman with multiple complications during a revision tracheotomy including subcutaneous emphysema and a pneumothorax. Management of her airway was complicated by a history of recurrent follicular B-cell lymphoma associated with extensive cervical lymphadenopathy. We detail the importance of heightened clinical awareness and the use of intraoperative safety adjuncts when performing revision tracheostomies.

Small-Molecule Chemical Probes For The Potential Therapeutic Targets In Alcoholic Liver Diseases, Ashish Dogra, Feng Li

Faculty, Staff and Students Publications

Alcoholic liver disease (ALD) encompasses a range of conditions resulting from prolonged and excessive alcohol consumption, causing liver damage such as alcoholic fatty liver, inflammation, fibrosis, and cirrhosis. Alcohol consumption contributes to millions of deaths each year. So far, the effective treatments for ALD are limited. To date, the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption, and only few specialized medicines are in the market for the treatment of patients suffering from ALD. Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development. In this review, we …

Deficiencies With Cage-Aid Questionnaire In Identifying Nonmedical Opioid Use-A Report Of Two Cases, Jaya Amaram-Davila, Patricia Bramati, Laura Gammon, Tarun Mallipeddi, Olivia Jastrzemski, Matthew D Clark, Joseph Arthur, Akhila Reddy, Eduardo Bruera

Faculty, Staff and Students Publications

Background: The CAGE-AID questionnaire (Cut-down, Annoyed, Guilty, Eye-opener scale Adapted to Include Drugs) is used to screen patients for substance use disorder and nonmedical opioid use (NMOU). Major pain guidelines encourage using such screening tools for all patients including cancer patients before initiating opioids. We present two cases where the CAGE-AID results did not accurately identify the risk for NMOU.

Case description: Patient 1 is a male in his 60s with metastatic prostate cancer was admitted for uncontrolled pain. Imaging revealed extensive spinal metastasis, needing initiation of methadone and hydromorphone. The CAGE-AID score was positive, placing him at risk for …

Revisiting The Use Of Antibiotics To Prevent Copd Exacerbation: Is Doxycycline The Answer?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Il17a Blockade With Ixekizumab Suppresses Muvb Signaling In Clinical Psoriasis, Scott A Ochsner, Mesias Pedroza, Rudolf T Pillich, Venkatesh Krishnan, Bruce W Konicek, Ernst R Dow, So Young Park, Sandeep K Agarwal, Neil J Mckenna

Faculty, Staff and Students Publications

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets …

Public Reporting For Coronary Artery Bypass Graft Surgery: The Quest For The Optimal Scorecard, Hiba Ghandour, Aaron J Weiss, Mario Gaudino, Michael Halkos, Danny Chu, Bradley S Taylor, John Puskas, Deepak L Bhatt, Marco Zenati, John Stulak, Todd Rosengart, Husam H Balkhy, Eugene H Blackstone, Lars G Svensson, Faisal G Bakaeen, Ozgun Erten, Tara Karamlou, Edward G Soltesz, A Marc Gillinov, Anthony Warmuth, Eric E Roselli, Nicholas G Smedira

Faculty, Staff and Students Publications

Objective: A number of publicly available rating algorithms are used to assess hospital performance in coronary artery bypass grafting (CABG). However, concerns remain that these algorithms fail to correlate with each other and inadequately capture the case complexity of individual center practices.

Methods: Composite star ratings for isolated CABG from the Society of Thoracic Surgeons public reporting database were extracted for 2018-2019. U.S. News & World Report Best Hospitals was used to extract CABG ratings as well as overall cardiology and heart surgery ranking, and the Centers for Medicare & Medicaid Services Hospital Compare was used to extract CABG volume …

A Novel Grk3-Hdac2 Regulatory Pathway Is A Key Direct Link Between Neuroendocrine Differentiation And Angiogenesis In Prostate Cancer Progression, Samira Naderinezhad, Guoliang Zhang, Zheng Wang, Dayong Zheng, Mohit Hulsurkar, Michael Bakhoum, Ning Su, Han Yang, Tao Shen, Wenliang Li

Faculty, Staff and Students Publications

The mechanisms underlying the progression of prostate cancer (PCa) to neuroendocrine prostate cancer (NEPC), an aggressive PCa variant, are largely unclear. Two prominent NEPC phenotypes are elevated NE marker expression and heightened angiogenesis. Identifying the still elusive direct molecular links connecting angiogenesis and neuroendocrine differentiation (NED) is crucial for our understanding and targeting of NEPC. Here we found that histone deacetylase 2 (HDAC2), whose role in NEPC has not been reported, is one of the most upregulated epigenetic regulators in NEPC. HDAC2 promotes both NED and angiogenesis. G protein-coupled receptor kinase 3 (GRK3), also upregulated in NEPC, is a critical …

Immune Infiltration In Tumor And Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes In Early-Stage Lung Cancer, Chao Cheng, Thinh T Nguyen, Mabel Tang, Xinan Wang, Chongming Jiang, Yanhong Liu, Ivan Gorlov, Olga Gorlova, John Iafrate, Michael Lanuti, David C Christiani, Christopher I Amos

Faculty, Staff and Students Publications

INTRODUCTION: In recent years, the proportion of patients with NSCLC diagnosed at an early stage has increased continuously.

METHODS: In this study, we analyzed samples and data collected from 119 samples from 67 early stage patients with NSCLC, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-sequencing analysis with high sequencing depth.

RESULTS: We found that immune-related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples than in tumor samples. In survival analysis, the infiltration of certain immune cell types in tumor, but not adjacent …

Disparities In Cancer Mortality Patterns: A Comprehensive Examination Of Us Rural And Urban Adults, 1999–2020, Itunu O Sokale, Syed Ahsan Raza, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cancer mortality rates overall in the U.S. have decreased significantly; however, the rate of decline has not been uniform across sociodemographic groups. We aimed to compare trends in cancer mortality rates from 1999 to 2020 between rural and urban individuals and to examine whether any rural-urban differences are uniform across racial and ethnic groups.

METHODS: We used U.S.-wide data from the National Center for Health Statistics, for all cancer deaths among individuals aged 25 years or older. We estimated average annual percentage change (AAPC) in age-standardized cancer mortality rates in the U.S. by cancer type, rural-urban status, sex, and …

The Transcription Factor Chrebp Links Mitochondrial Lipidomes To Mitochondrial Morphology And Progression Of Diabetic Kidney Disease, Li Li, Jianyin Long, Koki Mise, Naravat Poungavrin, Philip L Lorenzi, Iqbal Mahmud, Lin Tan, Pradip K Saha, Yashpal S Kanwar, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

A substantial body of evidence has established the contributions of both mitochondrial dynamics and lipid metabolism to the pathogenesis of diabetic kidney disease (DKD). However, the precise interplay between these two key metabolic regulators of DKD is not fully understood. Here, we uncover a link between mitochondrial dynamics and lipid metabolism by investigating the role of carbohydrate-response element-binding protein (ChREBP), a glucose-responsive transcription factor and a master regulator of lipogenesis, in kidney podocytes. We find that inducible podocyte-specific knockdown of ChREBP in diabetic db/db mice improves key biochemical and histological features of DKD in addition to significantly reducing mitochondrial fragmentation. …

Association Between Right Heart Catheterization Hemodynamics And Glycosylated Hemoglobin Levels In Adults With Heart Failure With Reduced Ejection Fraction, Gaspar Del Rio-Pertuz, Cristina Morataya, Kanak Parmar, Zeyad Elharabi, Daniel Davis, Mostafa Abohelwa, Ozman Ochoa, Alison Tran, Kenneth Nugent, David Paniagua, Erwin Argueta-Sosa

Faculty, Staff and Students Publications

UNLABELLED: This study hypothesized that elevated glycosylated hemoglobin (HbA1c) levels are associated with abnormal right heart catheterization (RHC) hemodynamic parameters in patients with heart failure with reduced ejection fraction (HFrEF) and no prior diagnosis of diabetes.

METHODS: Retrospective cohort study of adult patients with HFrEF and no prior diagnosis of diabetes who underwent RHC and had HbA1c levels measured 30 days before or after the RHC. This study excluded patients who had received blood transfusions within 90 days prior to HbA1c measurement and patients with known diabetes. Univariate and multivariate regression analyses adjusted for age, sex, and BMI were used …

A Defect In Mitochondrial Fatty Acid Synthesis Impairs Iron Metabolism And Causes Elevated Ceramide Levels, Debdeep Dutta, Oguz Kanca, Seul Kee Byeon, Paul C Marcogliese, Zhongyuan Zuo, Rishi V Shridharan, Jun Hyoung Park, Undiagnosed Diseases Networ, Guang Lin, Ming Ge, Gali Heimer, Jennefer N Kohler, Matthew T Wheeler, Benny A Kaipparettu, Akhilesh Pandey, Hugo J Bellen

Faculty, Staff and Students Publications

In most eukaryotic cells, fatty acid synthesis (FAS) occurs in the cytoplasm and in mitochondria. However, the relative contribution of mitochondrial FAS (mtFAS) to the cellular lipidome is not well defined. Here we show that loss of function of Drosophila mitochondrial enoyl coenzyme A reductase (Mecr), which is the enzyme required for the last step of mtFAS, causes lethality, while neuronal loss of Mecr leads to progressive neurodegeneration. We observe a defect in Fe-S cluster biogenesis and increased iron levels in flies lacking mecr, leading to elevated ceramide levels. Reducing the levels of either iron or ceramide suppresses the neurodegenerative …

The Reviewer Academy Of The Society Of Critical Care Medicine: Key Principles And Strategic Plan, Peta M A Alexander, Rebecca A Aslakson, Erin F Barreto, Jan Hau Lee, Heather Meissen, Brenda M Morrow, Lama Nazer, Richard D Branson, Kirby P Mayer, Natalie Napolitano, Meghan B Lane-Fall, Andrea Sikora, Preeti R John, R Phillip Dellinger, Margaret Parker, Andrew Argent, Adjoa Boateng, Thomas P Green, Sapna R Kudchadkar, David M Maslove, Megan A Rech, Lauren R Sorce, Robert C Tasker, Timothy G Buchman, Paul A Checchia

Faculty, Staff and Students Publications

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected …

Differences In Hyperandrogenism Related To Early Detection Of Non-Classical Congenital Adrenal Hyperplasia On Second Newborn Screen, Bonnie Mccann-Crosby, Mark C Liang, Mitchell E Geffner, Christina M Koppin, Nicole R Fraga, V Reid Sutton, Lefkothea P Karaviti, Gagandeep Bhullar, Mimi S Kim

Faculty, Staff and Students Publications

Screening for congenital adrenal hyperplasia (CAH) remains heterogenous across geographies—we sought to determine the proportion of non-classical CAH (NCAH) detection by one vs. two newborn screens (NBS) in two U.S. regions. Data were collected at tertiary centers in Houston (HOU) and Los Angeles (LA) on 35 patients with NCAH, comparing patients identified via the NBS vs. during childhood, 17-hydroxyprogesterone (17-OHP) levels, genotype, and phenotype. The NBS filter-paper 17-OHP levels and daily cutoffs were recorded on initial and second screens. In all, 53% of patients with NCAH in the HOU cohort were identified as infants via the second NBS. Patients identified …

Comparison Of Bivalent And Monovalent Sars-Cov-2 Variant Vaccines: The Phase 2 Randomized Open-Label Covail Trial, Angela R Branche, Nadine G Rouphael, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Evan J Anderson, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Elissa Malkin, Jeffrey M Bethony, Edward E Walsh, Daniel S Graciaa, Hady Samaha, Amy C Sherman, Stephen R Walsh, Getahun Abate, Zacharoula Oikonomopoulou, Hana M El Sahly, Thomas C S Martin, Satoshi Kamidani, Michael J Smith, Benjamin G Ladner, Laura Porterfield, Maya Dunstan, Anna Wald, Tamia Davis, Robert L Atmar, Mark J Mulligan, Kirsten E Lyke, Christine M Posavad, Megan A Meagher, David S Stephens, Kathleen M Neuzil, Kuleni Abebe, Heather Hill, Jim Albert, Kalyani Telu, Jinjian Mu, Teri C Lewis, Lisa A Giebeig, Amanda Eaton, Antonia Netzl, Samuel H Wilks, Sina Türeli, Mamodikoe Makhene, Sonja Crandon, David C Montefiori, Mat Makowski, Derek J Smith, Seema U Nayak, Paul C Roberts, John H Beigel, Covail Study Group

Faculty, Staff and Students Publications

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs …

Safety And Efficacy Of Long-Term Deutetrabenazine Use In Children And Adolescents With Tics Associated With Tourette Syndrome: An Open-Label Extension Study, Joseph Jankovic, Barbara Coffey, Daniel O Claassen, Joohi Jimenez-Shahed, Barry J Gertz, Elizabeth A Garofalo, David A Stamler, Maria Wieman, Juha-Matti Savola, Eran Harary, Jessica Alexander, Hadas Barkay, Mark Forrest Gordon

Faculty, Staff and Students Publications

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics.

OBJECTIVE: To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS.

METHODS: Alternatives for Reducing Tics in TS (ARTISTS) open-label extension (OLE) (NCT03567291) was a 54-week, global, phase 3, open-label extension study of deutetrabenazine (6-48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2-week randomized withdrawal period. Participants (6-16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by …

Characterization And Quantification Of Adeno-Associated Virus Capsid-Loading States By Multi-Wavelength Analytical Ultracentrifugation With Ultrascan, Amy Henrickson, Xiaozhe Ding, Austin G Seal, Zhe Qu, Lauren Tomlinson, John Forsey, Viviana Gradinaru, Kazuhiro Oka, Borries Demeler

Faculty, Staff and Students Publications

Aim:

We present multi-wavelength (MW) analytical ultracentrifugation (AUC) methods offering superior accuracy for adeno-associated virus characterization and quantification.

Methods:

Experimental design guidelines are presented for MW sedimentation velocity and analytical buoyant density equilibrium AUC.

Results:

Our results were compared with dual-wavelength AUC, transmission electron microscopy and mass photometry. In contrast to dual-wavelength AUC, MW-AUC correctly quantifies adeno-associated virus capsid ratios and identifies contaminants. In contrast to transmission electron microscopy, partially filled capsids can also be detected and quantified. In contrast to mass photometry, first-principle results are obtained.

Conclusion:

Our study demonstrates the improved information provided by MW-AUC, highlighting the utility …

Transfusion Reactions Associated With Covid-19 Convalescent Plasma In Outpatient Clinical Trials, Moises A Huaman, Jay S Raval, James H Paxton, Giselle S Mosnaim, Bela Patel, Shweta Anjan, Barry R Meisenberg, Adam C Levine, Christi E Marshall, Anusha Yarava, Aarthi G Shenoy, Sonya L Heath, Judith S Currier, Yuriko Fukuta, Janis E Blair, Emily S Spivak, Joann R Petrini, Patrick B Broderick, William Rausch, Marieelena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Seble G Kassaye, Malathi Ram, Ying Wang, Piyali Das, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Daniel E Ford, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, Stephan Ehrhardt, Bryan Lau, Sheriza N Baksh, David M Shade, Arturo Casadevall, Daniel F Hanley, Jiangda Ou, Thomas J Gniadek, Alyssa Ziman, Shmuel Shoham, Kelly A Gebo, Evan M Bloch, Aaron A R Tobian, David J Sullivan, Jonathan M Gerber

Faculty, Staff and Students Publications

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.

RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 …