Digital Commons Network^™

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Steven L Mcafee, Aj S Bottoms, Vesselina Toncheva, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Faculty, Staff and Student Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

High All-Cause Mortality And Increasing Proportion Of Older Adults With Tuberculosis In Texas, 2008–2020, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Lana Yamba, Blanca I Restrepo

Faculty, Staff and Student Publications

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Distinct Autoantibody Profiles Across Checkpoint Inhibitor Types And Toxicities, Hong Mu-Mosley, Mitchell S Von Itzstein, Farjana Fattah, Jialiang Liu, Chengsong Zhu, Yang Xie, Edward K Wakeland, Jason Y Park, Brad S Kahl, Catherine S Diefenbach, David E Gerber

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymphoma. Cycle 2 Day 1 (C2D1) autoantibody levels were compared to pre-treatment baseline. Across 112 autoantibodies tested, we generally observed increases in ipilimumab-containing regimens, with decreases noted in the nivolumab arm. Among 15 autoantibodies with significant changes at C2D1, all nivolumab cases exhibited decreases, with more than 90% of ipilimumab-exposed cases showing increases. Autoantibody …

Global Prevalence Of Aspirin Use For Primary Prevention Of Cardiovascular Disease: A Cross-Sectional Study Of Nationally Representative, Individual-Level Data, Sang Gune K Yoo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Neoadjuvant Chemoimmunotherapy For Nsclc: A Systematic Review And Meta-Analysis, Mark Sorin, Connor Prosty, Louis Ghaleb, Kathy Nie, Khaled Katergi, Muhammad H Shahzad, Laurie-Rose Dubé, Aline Atallah, Anikka Swaby, Matthew Dankner, Trafford Crump, Logan A Walsh, Pierre O Fiset, Boris Sepesi, Patrick M Forde, Tina Cascone, Mariano Provencio, Jonathan D Spicer

Faculty, Staff and Student Publications

IMPORTANCE: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

OBJECTIVE: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

DATA SOURCES: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of …

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Student Publications

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

Design, setting, and participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Caron A Jacobson, Sairah Ahmed, David B Miklos, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

Factors Associated With The Ability Of Us Nursing Homes To Accept Residents With Severe Obesity, Cynthia Mcmahan, Bianca Shieu, Alison Trinkoff, Nicholas Castle, David G Wolf, Steven Handler, John A Harris

Faculty, Staff and Student Publications

Objectives: Severe obesity in nursing home (NH) residents is associated with specialized care needs, limited mobility, and challenges in daily living. The COVID-19 pandemic strained NH resources and exacerbated staffing shortages. This study aimed to assess the ability of US NHs to accept and care for residents with severe obesity post-COVID, as well as associated NH factors.

Design: Cross-sectional nationwide survey of NH administrators (2021-2022).

Setting and participants: 290 NHs from a national sample (n = 224) and a targeted sample in Massachusetts and New Jersey (n = 66).

Methods: A survey designed to assess how NHs approach admitting and …

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals: A Secondary Cross-Protocol Analysis Of 4 Randomized Trials, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

IMPORTANCE: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

OBJECTIVE: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Assessment Of Illness Severity In Adults Hospitalized With Acute Respiratory Tract Infection Due To Influenza, Respiratory Syncytial Virus, Or Human Metapneumovirus, Ann R Falsey, Edward E Walsh, Stacey L House, Yannick Vandendijck, Marita Stevens, Eric K H Chan, Gabriela Ispas

2020-Current year OA Pubs

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs).

METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection …

A Physiological Approach To Renal Clearance: From Premature Neonates To Adults, Nick Holford, Conor J. O'Hanlon, Karel Allegaert, Brian Anderson, Amilcar Falcão, Nicolas Simon, Yoke Lin Lo, Alison H. Thomson, Catherine M.T. Sherwin, Evelyne Jacqz-Aigrain, Carolina Llanos-Paez, Stefanie Hennig, Linas Mockus, Carl Kirkpatrick

Pediatrics Faculty Publications

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct …

Does A Reduction In Receiving Assistance With Daily Activities Among Older Adults In Mexico Indicate An Increase In Unmet Needs Or A Decrease In Needs For Care?, Brian Downer, Rafael Samper-Ternent, Philip Cantu, Matthew Miller, Rebeca Wong

Faculty, Staff and Student Publications

OBJECTIVES: The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

METHODS: We selected Mexican Health and Aging Study participants aged 60-76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if …

Potential Impact Of Annual Vaccination With Reformulated Covid-19 Vaccines: Lessons From The Us Covid-19 Scenario Modeling Hub, Sung-Mok Jung, Sara L Loo, Emily Howerton, Lucie Contamin, Claire P Smith, Erica C Carcelén, Katie Yan, Samantha J Bents, John Levander, Jessi Espino, Joseph C Lemaitre, Koji Sato, Clifton D Mckee, Alison L Hill, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Alessandro Vespignani, Erik T Rosenstrom, Sebastian A Rodriguez-Cartes, Julie S Ivy, Maria E Mayorga, Julie L Swann, Guido España, Sean Cavany, Sean M Moore, T Alex Perkins, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srini Venkatramanan, Aniruddha Adiga, Benjamin Hurt, Brian Klahn, Joseph Outten, Jiangzhuo Chen, Henning Mortveit, Amanda Wilson, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Anil Vullikanti, Bryan Lewis, Madhav Marathe, Harry Hochheiser, Michael C Runge, Katriona Shea, Shaun Truelove, Cécile Viboud, Justin Lessler

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval).

METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Faculty, Staff and Student Publications

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19: A Secondary Analysis Of The Activ-1 Im Randomized Clinical Trial, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik, Activ-1 Im Study Group

2020-Current year OA Pubs

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Prescription And Dispensation Of Qt-Prolonging Medications In Individuals Receiving Hemodialysis, Virginia Wang, Chin-Hua Lily Wang, Magdalene M Assimon, Patrick H Pun, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

IMPORTANCE: Individuals with dialysis-dependent kidney failure have numerous risk factors for medication-related adverse events, including receipt of care by multiple clinicians and initiation of some QT-prolonging medications with known risk of torsades de pointes (TdP), which is associated with higher risk of sudden cardiac death. Little is known about the prescription and dispensation patterns of QT-prolonging medications among people receiving dialysis, hindering efforts to reduce drug-related harm from these and other medications in this high-risk population.

OBJECTIVE: To examine prescription and dispensation patterns of QT-prolonging medications with known TdP risk and selected interacting medications prescribed to individuals receiving hemodialysis.

DESIGN, …

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

Efficacy And Feasibility Of Short-Stretch Compression Therapy For Filarial Lymphedema In Sri Lanka, Jaimee M Hall, Nirmitha Lalindi De Silva, Janaka Ruben, Sandani S Thilakarathne, Thishan Channa Yahathugoda, Philip J Budge

2020-Current year OA Pubs

The WHO-recommended essential package of care (EPC) for filarial limb lymphedema consists of daily limb washing, entry lesion management, limb protection, exercises, and elevation. Decongestive therapy (DT) with compression bandaging by trained lymphedema therapists adds additional benefit but is unavailable for most in low- and middle-income countries (LMICs). To determine whether DT using self-adjustable, short-stretch compression garments (SSCG), prefitted using portable, three-dimensional infrared imaging (3DII), would be effective and feasible in LMIC settings, we conducted a pilot 6-week, interventional, single-group, open-label pilot study in Galle, Sri Lanka. Ten participants with Dreyer stage 3 lymphedema used SSCG for 2 weeks after …

Case 9-2024: An 84-Year-Old Man With A Fall, Zaven Sargsyan, Sunita D Srivastava, Virginia A Triant, Brian B Ghoshhajra

Faculty, Staff and Students Publications

No abstract provided.

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

Outpatient Covid-19 Convalescent Plasma Recipient Antibody Thresholds Correlated To Reduced Hospitalizations Within A Randomized Trial, Han-Sol Park, Anna Yin, Caelan Barranta, John S Lee, Christopher A Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E Fernandez, Owen R Baker, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie Elena 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, Jay S Raval, Seble G Kassaye, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N Baksh, Janna R Shapiro, Jiangda Ou, Yu Bin Na, Maria D Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J Betenbaugh, Alyssa Ziman, Daniel F Hanley, Arturo Casadevall, Shmuel Shoham, Evan M Bloch, Kelly A Gebo, Aaron Ar Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND

COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.

METHODS

This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors …

The Immunopathological Landscape Of Human Pre-Tcrα Deficiency: From Rare To Common Variants., Marie Materna, Ottavia M Delmonte, Marita Bosticardo, Mana Momenilandi, Peyton E Conrey, Bénédicte Charmeteau-De Muylder, Clotilde Bravetti, Rebecca Bellworthy, Axel Cederholm, Frederik Staels, Christian A Ganoza, Samuel Darko, Samir Sayed, Corentin Le Floc'h, Masato Ogishi, Darawan Rinchai, Andrea Guenoun, Alexandre Bolze, Taushif Khan, Adrian Gervais, Renate Krüger, Mirjam Völler, Boaz Palterer, Mahnaz Sadeghi-Shabestari, Anne Langlois De Septenville, Chaim A Schramm, Sanjana Shah, John J Tello-Cajiao, Francesca Pala, Kayla Amini, Jose S Campos, Noemia Santana Lima, Daniel Eriksson, Romain Lévy, Yoann Seeleuthner, Soma Jyonouchi, Manar Ata, Fatima Al Ali, Anna Stittrich, Caroline Deswarte, Anaïs Pereira, Jérôme Mégret, Tom Le Voyer, Paul Bastard, Laureline Berteloot, Michaël Dussiot, Natasha Vladikine, Paula P Cardenas, Emmanuelle Jouanguy, Mashael Alqahtani, Amal Hasan, Thangavel Alphonse Thanaraj, Jérémie Rosain, Fahd Al Qureshah, Vito Sabato, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Flore Rozenberg, Elie Haddad, Jose R Regueiro, Maria L Toribio, Judith R Kelsen, Mansoor Salehi, Shahram Nasiri, Mehdi Torabizadeh, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Nasimeh Vatandoost, Hossein Moravej, Seyed Mohammad Akrami, Mohsen Mazloomrezaei, Aurélie Cobat, Isabelle Meyts, Etsushi Toyofuku, Madoka Nishimura, Kunihiko Moriya, Tomoyuki Mizukami, Kohsuke Imai, Laurent Abel, Bernard Malissen, Fahd Al-Mulla, Fowzan Sami Alkuraya, Nima Parvaneh, Horst Von Bernuth, Christian Beetz, Frédéric Davi, Daniel C Douek, Rémi Cheynier, David Langlais, Nils Landegren, Nico Marr, Tomohiro Morio, Mohammad Shahrooei, Rik Schrijvers, Sarah E Henrickson, Hervé Luche, Luigi D Notarangelo, Jean-Laurent Casanova, Vivien Béziat

Faculty Research 2024

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–a T cell receptor (pre-TCRa) expression. Low circulating naive ab T cell counts at birth persisted over time, with normal memory ab and high gd T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue ab T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive ab T cell …

Efficacy And Safety Of Rezafungin And Caspofungin In Candidaemia And Invasive Candidiasis: Pooled Data From Two Prospective Randomised Controlled Trials, George R Thompson 3rd, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.

METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) …

Declining Prevalence Of Trichomonas Vaginalis Diagnosed By Wet Mount In A Cohort Of U.S. Women With And Without Hiv, Elizabeth M Daubert, Jodie Dionne, Jessica Atrio, Andrea K Knittel, Seble G Kassaye, Dominika Seidman, Amanda Long, Susan Brockmann, Igho Ofotokun, Margaret A Fischl, L Stewart Massad, Kathleen M Weber

2020-Current year OA Pubs

No abstract provided.

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …

Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham

Faculty, Staff and Students Publications

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs).

Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).

Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the …

Prevention And Potential Treatment Strategies For Respiratory Syncytial Virus, Bo-Wen Sun, Peng-Peng Zhang, Zong-Hao Wang, Xia Yao, Meng-Lan He, Rui-Ting Bai, Hao Che, Jing Lin, Tian Xie, Zi Hui, Xiang-Yang Ye, Li-Wei Wang

Faculty, Staff and Student Publications

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and …

Pharmacokinetic-Pharmacodynamic Evidence From A Phase 3 Trial To Support Flat-Dosing Of Rifampicin For Tuberculosis, Huy X. Ngo, Ava Y. Xu, Gustavo E. Velásquez, Nan Zhang, Vincent K. Chang, Ekaterina V. Kurbatova, William C. Whitworth, Erin Sizemore, Kia Bryant, Wendy Carr, Marc Weiner, Kelly E. Dooley, Melissa Engle, Susan E. Dorman, Payam Nahid, Susan Swindells, Richard E. Chaisson, Pheona Nsubuga, Madeleine Lourens, Rodney Dawson, Radojka M. Savic

Journal Articles: Infectious Diseases

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes.

METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months; TB-related unfavorable outcomes at 9, 12, and 18 months using …

Highly Variable Timing Renders Immunotherapy Efficacy And Toxicity Impractical Biomarkers Of One Another In Clinical Practice, Mitchell S Von Itzstein, Yuqiu Yang, Yiqing Wang, David Hsiehchen, Thomas Y Sheffield, Farjana Fattah, Vinita Popat, Murtaza Ahmed, Jade Homsi, Jonathan E Dowell, Sawsan Rashdan, Jay Lohrey, Hans J Hammers, Randall S Hughes, Tao Wang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.

Methods: Using …