Digital Commons Network^™

Ultrapotent Broadly Neutralizing Human-Llama Bispecific Antibodies Against Hiv-1, Jianliang Xu, Tongqing Zhou, Krisha Mckee, Baoshan Zhang, Cuiping Liu, Alexandra F Nazzari, Amarendra Pegu, Chen-Hsiang Shen, Jordan E Becker, Michael F Bender, Payton Chan, Anita Changela, Ridhi Chaudhary, Xuejun Chen, Tal Einav, Young Do Kwon, Bob C Lin, Mark K Louder, Jonah S Merriam, Nicholas C Morano, Sijy O'Dell, Adam S Olia, Reda Rawi, Ryan S Roark, Tyler Stephens, I-Ting Teng, Emily Tourtellott-Fogt, Shuishu Wang, Eun Sung Yang, Lawrence Shapiro, Yaroslav Tsybovsky, Nicole A Doria-Rose, Rafael Casellas, Peter D Kwong

Faculty, Staff and Student Publications

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM …

Provider Experiences With Daily Use Of Elastomeric Half-Mask Respirators In Health Care, Morgan Lane, Lisa Pompeii, Janelle Rios, Elisa Benavides, Marie Kasbaum, Scott Patlovich, Luis Ostrosky-Zeichner, Adam Hornbeck, Caitlin Mcclain, Rohan Fernando, Margaret Sietsema, Colleen Kraft

Faculty, Staff and Student Publications

Background: During public health emergencies, demand for N95 filtering facepiece respirators (N95 FFRs) can outpace supply. Elastomeric half-mask respirators (EHMRs) are a potential alternative that are reusable and provide the same or higher levels of protection. This study sought to examine the practical aspects of EHMR use among health care personnel (HCP).

Methods: Between September and December 2021, 183 HCPs at 2 tertiary referral centers participated in this 3-month EHMR deployment, wearing the EHMR whenever respiratory protection was required according to hospital protocols (ie, when an N95 FFR would typically be worn) and responding to surveys about their experience.

Results: …

Sequencing Of Kaposi’S Sarcoma Herpesvirus (Kshv) Genomes From Persons Of Diverse Ethnicities And Provenances With Kshv-Associated Diseases Demonstrate Multiple Infections, Novel Polymorphisms, And Low Intra-Host Variance, Vickie A Marshall, Elena M Cornejo Castro, Charles A Goodman, Nazzarena Labo, Isabella Liu, Nicholas C Fisher, Kyle N Moore, Ananthakrishnan Nair, Taina Immonen, Brandon F Keele, Mark N Polizzotto, Thomas S Uldrick, Yunxiang Mu, Tanuja Saswat, Laurie T Krug, Kevin M Mcbride, Kathryn Lurain, Ramya Ramaswami, Robert Yarchoan, Denise Whitby

Faculty, Staff and Student Publications

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. …

Health-Related Quality Of Life In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, Bortezomib, And Dexamethasone: Patient-Reported Outcomes From Griffin, Rebecca Silbermann, Jacob Laubach, Jonathan L Kaufman, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Katharine S Gries, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

In the phase 2 GRIFFIN trial (ClinicalTrials.gov identifier: NCT02874742), daratumumab added to lenalidomide, bortezomib, and dexamethasone (D-RVd) improved depth of response and progression-free survival (PFS) versus lenalidomide, bortezomib, and dexamethasone (RVd) alone in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) collected using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30-item (QLQ-C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module 20-item (QLQ-MY20), and EuroQol 5-Dimension 5-Level (EQ-5D-5L) tools on day 1 of cycles 1, 2, and 3; on day 21 of cycle 4 (end of …

Mycophenolate Mofetil Is Associated With Inferior Overall Survival In Cytomegalovirus-Seropositive Patients With Acute Myeloid Leukemia Undergoing Hematopoietic Cell Transplantation, Rima M Saliba, Stephanie J Lee, Paul A Carpenter, Geoffrey R Hill, Catherine J Lee, Amin Alousi, May Daher, George Chen, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall, Rohtesh S Mehta

Faculty, Staff and Student Publications

No abstract provided.

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, Valeria Fumagalli, Dominic Van Den Heuvel, Larissa Belz, Gulnoza Sobirova, Zhe Zhang, Anna Titova, Alejandro Martinez Navarro, Kami Pekayvaz, Michael Lorenz, Louisa Von Baumgarten, Jan Kranich, Tobias Straub, Bastian Popper, Vanessa Zheden, Walter Anton Kaufmann, Chenglong Guo, Guido Piontek, Saskia Von Stillfried, Peter Boor, Marco Colonna, Sebastian Clauß, Christian Schulz, Thomas Brocker, Barbara Walzog, Christoph Scheiermann, William C Aird, Claus Nerlov, Konstantin Stark, Tobias Petzold, Stefan Engelhardt, Michael Sixt, Robert Hauschild, Martina Rudelius, Robert A J Oostendorp, Matteo Iannacone, Matthias Heinig, Steffen Massberg

Faculty, Staff and Student Publications

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK …

A Novel Treponema Pallidum Subspecies Pallidum Strain Associated With A Painful Oral Lesion Is A Member Of A Potentially Emerging Nichols-Related Subgroup, Maria Rosa Velasquez, Bridget D De Lay, Diane G Edmondson, Gary P Wormser, Steven J Norris, Kaitlin Cafferky, Eric Munzer, Ciril-Christian Rizk, Marina Keller

Faculty, Staff and Student Publications

Background: Early syphilitic lesions are typically painless; however, several recent case studies have included patients with tender lesions and no evidence of concurrent infections. Here we present the manifestations and serological and molecular findings of a patient from New York State with a painful tongue lesion.

Methods: The diagnosis of syphilis was based on a combination of physical examination, serologic, pathologic, and immunohistochemical findings. DNA obtained from a formalin-fixed, paraffin-embedded biopsy was used to characterize the infecting pathogen using polymerase chain reaction, multilocus sequence typing, and whole-genome sequencing methods.

Results: Polymerase chain reaction and multilocus sequence typing of the biopsy …

Impact Of Antiretroviral Therapy During Acute Or Early Hiv Infection On Virologic And Immunologic Outcomes: Results From A Multinational Clinical Trial, Trevor A Crowell, Justin Ritz, Lu Zheng, Asma Naqvi, Joshua C Cyktor, Joseph Puleo, Brian Clagett, Javier R Lama, Cecilia Kanyama, Susan J Little, Susan E Cohn, Sharon A Riddler, Ann C Collier, Sonya L Heath, Pornphen Tantivitayakul, Beatriz Grinsztejn, Roberto C Arduino, James F Rooney, Gert U Van Zyl, Robert W Coombs, Lawrence Fox, Jintanat Ananworanich, Joseph J Eron, Scott F Sieg, John W Mellors, Eric S Daar

Faculty, Staff and Student Publications

Objective: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.

Design: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia.

Methods: HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and …

Combination Therapy With Novel Agents For Acute Myeloid Leukaemia: Insights Into Treatment Of A Heterogenous Disease, Wei-Ying Jen, Hagop Kantarjian, Tapan M Kadia, Courtney D Dinardo, Ghayas C Issa, Nicholas J Short, Musa Yilmaz, Gautam Borthakur, Farhad Ravandi, Naval G Daver

Faculty, Staff and Student Publications

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1

Implementation Strategies To Improve Hiv Care Cascade Outcomes In Low- And Middle-Income Countries: A Systematic Review From 2014 To 2021, Sita Lujintanon, Ingrid Eshun-Wilson, Noelle Le Tourneau, Laura Beres, Sheree Schwartz, Stefan Baral, Ryan Thompson, Ashley Underwood, Branson Fox, Elvin H Geng, Christopher G Kemp

2020-Current year OA Pubs

INTRODUCTION: In low- and middle-income countries (LMICs), which are disproportionately affected by the HIV epidemic and manage limited resources, optimized implementation strategies are needed to enhance the efficiency of the HIV response. Assessing strategy usage to date could identify research gaps and inform future implementation efforts. We conducted a systematic review to describe the features and distributions of published implementation strategies attempting to improve HIV treatment service delivery and outcomes.

METHODS: We searched PubMed, Embase, and CINAHL and screened abstracts and full texts published between 1 January 2014 and 27 August 2021, for English-language studies conducted in LMICs that described …

Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings

2020-Current year OA Pubs

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies.

METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis …

Estimating The Potential Value Of Msm-Focused Evidence-Based Implementation Interventions In Three Ending The Hiv Epidemic Jurisdictions In The United States: A Model-Based Analysis, Benjamin Enns, Elvin H Geng, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Improving the delivery of existing evidence-based interventions to prevent and diagnose HIV is key to Ending the HIV Epidemic in the United States. Structural barriers in the access and delivery of related health services require municipal or state-level policy changes; however, suboptimal implementation can be addressed directly through interventions designed to improve the reach, effectiveness, adoption or maintenance of available interventions. Our objective was to estimate the cost-effectiveness and potential epidemiological impact of six real-world implementation interventions designed to address these barriers and increase the scale of delivery of interventions for HIV testing and pre-exposure prophylaxis (PrEP) in three …

Management Of Extracorporeal Membrane Oxygenation Anticoagulation In The Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Ariane Willems, Marc M Anders, Alejandro V Garcia, Adam M Vogel, Andrew R Yates, Jennifer A Muszynski, Peta M A Alexander, Katherine Steffen, Sitaram Emani, Alison Gehred, Elizabeth Lyman, Lakshmi Raman

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference.

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. Evidence tables were constructed …

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative (Peace) Consensus Conference, Peta M A Alexander, Melania M Bembea, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed S Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Christopher Almond, Marc M Anders, Gail M Annich, Leonardo R Brandão, Wayne Chandler, Megan Delaney, Robert Digeronimo, Sitaram Emani, Samir K Gadepalli, Alejandro V Garcia, Bereketeab Haileselassie, Robert Hyslop, Martin C J Kneyber, Lisa Baumann Kreuziger, Jennifer Le, Laura Loftis, Ali B V Mcmichael, D Michael Mcmullan, Paul Monagle, Kathleen Nicol, Matthew L Paden, Jason Patregnani, John Priest, Leslie Raffini, Lindsay M Ryerson, Steven R Sloan, Jun Teruya, Andrew R Yates, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.

DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any …

Progressive Thrombocytopenia, Splenomegaly, And Abnormal Tone In An Infant With Growth Faltering, Gal Barak, Gail Demmler-Harrison, Linda Rossetti, Venée N Tubman, Ameya S Walimbe, Rathi Asaithambi

Faculty, Staff and Students Publications

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but …

Priorities For Clinical Research In Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Jennifer A Muszynski, Melania M Bembea, Alison Gehred, Elizabeth Lyman, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Peta M A Alexander

Faculty, Staff and Students Publications

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus.

DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children.

DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third …

Dyspneic And Pink, Christian Inchaustegui, Sarvari Yellapragada, Jack Badawy, Ameer Ahmed, Andrew White, Zaven Sargsyan

Faculty, Staff and Students Publications

No abstract provided.

Anticoagulant Medications: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative Consensus Conference, Katherine Cashen, Arun Saini, Leonardo R Brandão, Jennifer Le, Paul Monagle, Katie M Moynihan, Lindsay M Ryerson, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski, Peta M A Alexander, Heidi J Dalton

Faculty, Staff and Students Publications

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the medications used for anticoagulation for pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE (PEACE).

DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION: Included studies assessed anticoagulation used in pediatric ECMO.

DATA EXTRACTION: Two authors reviewed all citations independently, with a third reviewer adjudicating any conflicts. Eighteen references were used for data extraction as well as for creation of recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS: …

Enteric Fever In Children: An Epidemiological And Clinical Review Of Cases In Southeast Texas, Zachary C Foughty, Denver T Niles, Andrea T Cruz

Faculty, Staff and Students Publications

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.

Advanced Hiv Disease And Associated Factors Among Young People Aged 15-24 Years At A Tertiary Hospital In Sierra Leone: A Cross-Sectional Study, Mamadu Baldeh, Samuel Kizito, Sulaiman Lakoh, Daniel Sesay, Samuel Adeyemi Williams, Umu Barrie, Frida Dennis, Dimbintsoa Rakotomalala Robinson, Franck Lamontagne, Franck Amahowe, Patrick Turay, Ozge Sensoy Bahar, Elvin Geng, Fred M Ssewamala

2020-Current year OA Pubs

BACKGROUND: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 - 24 years seeking medical services at a major public hospital in Sierra Leone.

METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone …

Changes In Plasma Concentrations Of Per- And Polyfluoroalkyl Substances After Bariatric Surgery In Adolescents From The Teen-Longitudinal Assessment Of Bariatric Surgery (Teen-Labs) Study, Brittney O Baumert, Sandrah P Eckel, Jesse A Goodrich, Zhenjiang Li, Nikos Stratakis, Douglas I Walker, Yinqi Zhao, Fabian Christoph Fischer, Scott Bartell, Damaskini Valvi, Xiangping Lin, Zoe Coates Fuentes, Thomas Inge, Justin Ryder, Todd Jenkins, Rohit Kohli, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate …

Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo

Faculty, Staff and Student Publications

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Update On Outbreak Of Fungal Meningitis Among Us Residents Who Received Epidural Anesthesia At Two Clinics In Matamoros, Mexico, Dallas J Smith, Jeremy A W Gold, Tom Chiller, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Vladimir Brian Gonzalez Cortes, Celida Duque Molina, Samantha Williams, Axel A Vazquez Deida, Katrina Byrd, Peter G Pappas, Thomas F Patterson, Nathan P Wiederhold, George R Thompson, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Background: Public health officials are responding to an outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at 2 clinics (River Side Surgical Center and Clinica K-3) in Matamoros, Mexico, during 1 January to 13 May 2023. This report describes outbreak epidemiology and outlines interim diagnostic and treatment recommendations.

Methods: Interim recommendations for diagnosis and management were developed by the Mycoses Study Group Research Education and Consortium (MSGERC) based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. …

A Randomized, Double-Blind, Phase 3 Safety And Efficacy Study Of Ridinilazole Versus Vancomycin For Treatment Of Clostridioides Difficile Infection: Clinical Outcomes With Microbiome And Metabolome Correlates Of Response, Pablo C Okhuysen, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI.

METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), …

Viral And Host Factors Are Associated With Mortality In Hospitalized Patients With Covid-19, Neil R Aggarwal, Jacquie Nordwall, Dominique L Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A Ginde, Awori J Hayanga, Helene Highbarger, Mark Holodniy, Juan P Horcajada, Mamta K Jain, Kami Kim, Sylvain Laverdure, Jens Lundgren, Ven Natarajan, Hien H Nguyen, Sarah L Pett, Andrew Phillips, Garyphallia Poulakou, David A Price, Philip Robinson, Angela J Rogers, Uriel Sandkovsky, Katy Shaw-Saliba, Jeffrey M Sturek, Barbara W Trautner, Michael Waters, Cavan Reilly

Faculty, Staff and Students Publications

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid …

A Phase 2 Clinical Trial To Evaluate The Safety, Reactogenicity, And Immunogenicity Of Different Prime-Boost Vaccination Schedules Of 2013 And 2017 A(H7n9) Inactivated Influenza Virus Vaccines Administered With And Without As03 Adjuvant In Healthy Us Adults, Christina A Rostad, Robert L Atmar, Emmanuel B Walter, Sharon Frey, Jeffery L Meier, Amy C Sherman, Lilin Lai, Rachel Tsong, Carol M Kao, Vanessa Raabe, Hana M El Sahly, Wendy A Keitel, Jennifer A Whitaker, Michael J Smith, Kenneth E Schmader, Geeta K Swamy, Getahun Abate, Patricia Winokur, Wendy Buchanan, Kaitlyn Cross, Ashley Wegel, Yongxian Xu, Inci Yildirim, Satoshi Kamidani, Nadine Rouphael, Paul C Roberts, Mark J Mulligan, Evan J Anderson

Center for Medical Ethics and Health Policy Staff Publications

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 …

Chagas Disease In Immunocompromised Patients, Eva H Clark, Louisa A Messenger, Jeffrey D Whitman, Caryn Bern

Faculty, Staff and Students Publications

As Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various …