Digital Commons Network^™

Apoe4, Age, And Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia, Jayakrishnan Nair, Joseph F. Welch, Alexandria B. Marciante, Tingting Hou, Qing Lu, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

Rational

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.

Objectives

Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).

Methods

In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures …

Irf7 And Unc93b1 Variants In An Infant With Recurrent Herpes Simplex Virus Infection., Megan H. Tucker, Wei Yu, Heather Menden, Sheng Xia, Carl F. Schreck, Margaret Gibson, Daniel A. Louiselle, T Pastinen, Nikita Raje, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a …

Selective Immune Suppression Using Interleukin-6 Receptor Inhibitors For Management Of Immune-Related Adverse Events, Faisal Fa'ak, Maryam Buni, Adewunmi Falohun, Huifang Lu, Juhee Song, Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Muhammad Osama Awiwi, Nourel Hoda Tahon, Khaled M Elsayes, Kaysia Ludford, Emma J Montazari, Julia Chernis, Maya Dimitrova, Sabina Sandigursky, Jeffrey A Sparks, Osama Abu-Shawer, Osama Rahma, Uma Thanarajasingam, Ashley M Zeman, Rafee Talukder, Namrata Singh, Sarah H Chung, Petros Grivas, May Daher, Ala Abudayyeh, Iman Osman, Jeffrey Weber, Jean H Tayar, Maria E Suarez-Almazor, Noha Abdel-Wahab, Adi Diab

Faculty, Staff and Student Publications

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.

METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.

RESULTS: We identified a total of 92 patients …

Dementias Among Older Males And Females In The U.S. Medicare System With And Without Hiv, Xiaoying Yu, Yong-Fang Kuo, Mukaila A Raji, Abbey B Berenson, Jacques Baillargeon, Thomas P Giordano

Faculty, Staff and Students Publications

Background: Despite the growing concern that people with HIV (PWH) will experience a disproportionate burden of dementia as they age, very few studies have examined the sex-specific prevalence of dementia, including Alzheimer disease and related dementias (AD/ADRD) among older PWH versus people without HIV (PWOH) using large national samples.

Methods: We constructed successive cross-sectional cohorts including all PWH aged 65+ years from U.S. Medicare enrollees and PWOH in a 5% national sample of Medicare data from 2007 to 2019. All AD/ADRD cases were identified by ICD-9-CM/ICD-10-CM diagnosis codes. Prevalence of AD/ADRD was calculated for each calendar year by sex-age strata. …

Physiological Age By Artificial Intelligence-Enhanced Electrocardiograms As A Novel Risk Factor Of Mortality In Kidney Transplant Candidates, Elizabeth C Lorenz, Isabella Zaniletti, Bradley K Johnson, Tanya M Petterson, Walter K Kremers, Carrie A Schinstock, Hatem Amer, Andrea L Cheville, Nathan K Lebrasseur, Wolfgang C Winkelmayer, Sankar D Navaneethan, Abraham Baez-Suarez, Zachi I Attia, Francisco Lopez-Jimenez, Paul A Friedman, Cassie C Kennedy, Andrew D Rule

Faculty, Staff and Students Publications

BACKGROUND: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality.

METHODS: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality.

RESULTS: Of the 2183 patients evaluated, 59.1% were male, …

Divergent Clinical Presentations And Outcomes Among Children And Adolescents With Kaposi Sarcoma In Malawi And Tanzania, Liane R Campbell, Allison Silverstein, Erin Peckham-Gregory, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Jason M Bacha, Carrie L Kovarik, Parth S Mehta, Toni Chanroo, Asulwisye Kapesa, Beatrice Malingoti, Rizine Mzikamanda, Nmazuo W Ozuah, Carl E Allen, Michael E Scheurer, Nader K El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.

Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania.

Results: …

Impact Of The Covid-19 Pandemic On The Education And Procedural Volume Of Fellows In Critical Care Medicine – A Cross-Sectional Survey, Orlando Garner, Kanta Velamuri, Kristen Staggers, Andrea Barbara Braun

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has changed the way medical education is delivered. The purpose of this study was to assess the impact of the COVID-19 pandemic on the education and procedural volume of critical care and pulmonary critical care fellows.

METHODS: We conducted a cross-sectional, internet-based, voluntary, anonymous, national survey of adult critical care fellows and academic attending physicians in critical care and pulmonary critical care fellowship programs in the United States between December 2020 and February 2021. Survey questions covered both didactic and non-didactic aspects of education and procedural volumes. Answers were ranked on a 5-point Likert scale. Survey …

Home-Based Tdcs For Apathy In Alzheimer’S Disease: A Protocol For A Randomized Double-Blinded Controlled Pilot Study, Antonio L Teixeira, Laís Bhering Martins, Thiago Macedo E Cordeiro, Lijin Jose, Robert Suchting, Holly M Holmes, Ron Acierno, Hyochol Ahn

Faculty, Staff and Student Publications

BACKGROUND: Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based …

Sex-Biased Immunological Processes Drive Hidradenitis Suppurativa, Kelly Z. Young, Peter Dimitrion, Li Zhou, Indra Adrianto, Qing-Sheng Mi

Dermatology Articles

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can manifest with abscesses, sinus tracts, and scarring in the intertriginous areas of the body. HS is characterized by immune dysregulation, featuring elevated levels of myeloid cells, T helper (Th) cells, and pro-inflammatory cytokines, particularly those involved in Th1- and Th17-mediated immunity. In most epidemiological studies, HS shows a strong female sex bias, with reported female-to-male ratios estimated at roughly 3:1, suggesting that sex-related factors contribute to HS pathophysiology. In this article, we review the role of intrinsic and extrinsic factors that contribute to immunological differences between the sexes and …

Adad2 Functions In Spermiogenesis And Pirna Biogenesis In Mice, Yonggang Lu, Ippei Nagamori, Hisato Kobayashi, Kanako Kojima-Kita, Kenjiro Shirane, Hsin-Yi Chang, Toru Nishimura, Takayuki Koyano, Zhifeng Yu, Julio M Castañeda, Makoto Matsuyama, Satomi Kuramochi-Miyagawa, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

BACKGROUND: Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.

OBJECTIVES: This study aimed to investigate the cause of male sterility in Adad2 mutant mice and to understand the molecular functions of ADAD2.

MATERIALS AND METHODS: Adad2 homozygous mutant mouse lines, Adad2

RESULTS: Adad2–/– and Adad2Δ/Δ mice exhibit male-specific sterility due to abnormal spermiogenesis. ADAD2 interacts with multiple RNA-binding proteins involved in …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Matthew D Neal, Lucy Z Kornblith, Michelle N Gong, Harmony R Reynolds, Mary Cushman, Andrew D Althouse, Patrick R Lawler, Bryan J Mcverry, Keri S Kim, Lisa Baumann Kreuziger, Scott D Solomon, Mikhail N Kosiborod, Scott M Berry, Grant V Bochicchio, Marco Contoli, Michael E Farkouh, Joshua D Froess, Sheetal Gandotra, Yonatan Greenstein, Erinn M Hade, Nicholas Hanna, Kristin Hudock, Robert C Hyzy, Fátima Ibáñez Estéllez, Nicole Iovine, Ashish K Khanna, Pooja Khatri, Bridget-Anne Kirwan, Matthew E Kutcher, Eric Leifer, George Lim, Renato D Lopes, Jose L Lopez-Sendon, James F Luther, Lilia Nigro Maia, John G Quigley, Lana Wahid, Jennifer G Wilson, Ryan Zarychanski, Andrei Kindzelski, Mark W Geraci, Judith S Hochman, Activ-4a Investigators

Faculty, Staff and Students Publications

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Grant V Bochicchio, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

Extended Analysis Of Hiv Infection In Cisgender Men And Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir For Hiv Prevention: Hptn 083, Mark A Marzinke, Jessica M Fogel, Zhe Wang, Estelle Piwowar-Manning, Ryan Kofron, Amber Moser, Pradip Bhandari, Ryann Gollings, Lane R Bushman, Lei Weng, Elias K Halvas, John Mellors, Peter L Anderson, Deborah Persaud, Craig W Hendrix, Marybeth Mccauley, Alex R Rinehart, Marty St Clair, Susan L Ford, James F Rooney, Adeola Adeyeye, Suwat Chariyalertsak, Kenneth Mayer, Roberto C Arduino, Myron S Cohen, Beatriz Grinsztejn, Brett Hanscom, Raphael J Landovitz, Susan H Eshleman

Faculty, Staff and Student Publications

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections …

Zoster-Associated Prothrombotic Plasma Exosomes And Increased Stroke Risk, Andrew N Bubak, Christina Coughlan, Janelle Posey, Anthony J Saviola, Christy S Niemeyer, Serena W R Lewis, Sara Bustos Lopez, Adriana Solano, Stephen K Tyring, Cassidy Delaney, Keith B Neeves, Ravi Mahalingam, Kirk C Hansen, Maria A Nagel

Faculty, Staff and Student Publications

Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited.

OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring.

DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC …

Tsks Localizes To Nuage In Spermatids And Regulates Cytoplasmic Elimination During Spermiation, Keisuke Shimada, Soojin Park, Seiya Oura, Taichi Noda, Akane Morohoshi, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding …

Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel

Faculty, Staff and Students Publications

Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …

Ideal Cardiovascular Health, Biomarkers, And Coronary Artery Disease In Persons With Hiv, Pamela S Douglas, Sara Mccallum, Michael T Lu, Triin Umbleja, Kathleen V Fitch, Borek Foldyna, Markella V Zanni, Evelynne S Fulda, Gerald S Bloomfield, Carl J Fichtenbaum, Edgar T Overton, Judith A Aberg, Carlos D Malvestutto, Tricia H Burdo, Roberto C Arduino, Ken S Ho, Michael T Yin, Heather J Ribaudo, Steven K Grinspoon

Faculty, Staff and Student Publications

OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).

DESIGN: Cross-sectional.

METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).

RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH …

Association Of Glucose-6-Phosphate Dehydrogenase Deficiency With Outcomes In Us Veterans With Covid-19, Sarah H Elsea, Javad Razjouyan, Kyung Min Lee, Julie A Lynch, Sharyl Martini, Lavannya M Pandit

Faculty, Staff and Students Publications

IMPORTANCE: The underlying biological risk factors for severe outcome due to SAR-CoV-2 infection are not well defined.

OBJECTIVE: To determine the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency and severity of COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included analysis of 24 700 veterans with G6PD enzyme testing prior to January 1, 2020, obtained through the US Veterans Health Administration national databases. These veterans were cross-referenced with the Veterans Administration COVID-19 Shared Data Resource for SARS-CoV-2 testing from February 15, 2020, to January 1, 2021. The final study population consisted of 4811 veterans who tested positive for SARS-CoV-2. Statistical …

State Variation In Squamous Cell Carcinoma Of The Anus Incidence And Mortality, And Association With Hiv/Aids And Smoking In The United States, Haluk Damgacioglu, Yueh-Yun Lin, Ana Patricia Ortiz, Chi-Fang Wu, Zahed Shahmoradi, Shiang Shiuan Shyu, Ruosha Li, Alan G Nyitray, Keith Sigel, Gary M Clifford, Naomi Jay, Vivian Colon Lopez, Gregory M Barnell, Elizabeth Y Chiao, Elizabeth A Stier, Karen J Ortiz-Ortiz, Jeslie M Ramos-Cartagena, Kalyani Sonawane, Ashish A Deshmukh

Faculty, Staff and Student Publications

PURPOSE: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues.

METHODS: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance …

Incidence And Clearance Of Anal Human Papillomavirus Infection In 16 164 Individuals, According To Human Immunodeficiency Virus Status, Sex, And Male Sexuality: An International Pooled Analysis Of 34 Longitudinal Studies, Feixue Wei, Marc T Goodman, Ningshao Xia, Jun Zhang, Anna R Giuliano, Gypsyamber D'Souza, Nancy A Hessol, Maarten F Schim Van Der Loeff, Jianghong Dai, Karin Neukam, Alexandra De Pokomandy, I Mary Poynten, Ronald B Geskus, Joaquin Burgos, Isabelle Etienney, Anna-Barbara Moscicki, Maria Gabriella Donà, Maura L Gillison, Alan G Nyitray, Rebecca G Nowak, Evy Yunihastuti, Huachun Zou, Carmen Hidalgo-Tenorio, Nittaya Phanuphak, Jean-Michel Molina, Alice M Schofield, Stephen Kerr, Song Fan, Yong Lu, Jason J Ong, Admire T Chikandiwa, Sirinya Teeraananchai, Nicola Squillace, Dorothy J Wiley, Joel M Palefsky, Damien Georges, Catharina J Alberts, Gary M Clifford

Faculty, Staff and Student Publications

Background: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.

Methods: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their …

Risk Factors For Ebola Virus Persistence In Semen Of Survivors In Liberia, Jonathan Dyal, Aaron Kofman, Jomah Z Kollie, John Fankhauser, Romeo Orone, Moses J Soka, Uriah Glaybo, Armah Kiawu, Edna Freeman, Giovanni Giah, Henry D Tony, Mylene Faikai, Mary Jawara, Kuku Kamara, Samuel Kamara, Benjamin Flowers, Mohammed L Kromah, Rodel Desamu-Thorpe, James Graziano, Shelley Brown, Maria E Morales-Betoulle, Deborah L Cannon, Kaihong Su, Susanne L Linderman, Mateusz Plucinski, Eric Rogier, Richard S Bradbury, W Evan Secor, Katherine E Bowden, Christi Phillips, Mary N Carrington, Yeon-Hwa Park, Maureen P Martin, Maria Del Pilar Aguinaga, Robert Mushi, Dana L Haberling, Elizabeth D Ervin, John D Klena, Moses Massaquoi, Tolbert Nyenswah, Stuart T Nichol, David E Chiriboga, Desmond E Williams, Steven H Hinrichs, Rafi Ahmed, Benjamin T Vonhm, Pierre E Rollin, Lawrence J Purpura, Mary J Choi

Faculty, Staff and Student Publications

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen.

METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within …

Safety And Tolerability Of Ser-109 As An Investigational Microbiome Therapeutic In Adults With Recurrent Clostridioides Difficile Infection: A Phase 3, Open-Label, Single-Arm Trial, Matthew D. Sims, Sahil Khanna, Paul Feuerstadt, Thomas J. Louie, Colleen R. Kelly, Edward S. Huang, Elizabeth L. Hohmann, Elaine E. L Wang, Caterina Oneto, Stuart H. Cohen, Charles S. Berenson, Louis Korman, Christine Lee, Bret Lashner, Colleen S. Kraft, Mayur Ramesh, Michael Silverman, Darrell S. Pardi, Ananya De, Asli Memisoglu, David A. Lombardi, Brooke R. Hasson, Barbara H. Mcgovern, Lisa Von Moltke

Infectious Diseases Articles

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR …

Circulation Of Rhinoviruses And/Or Enteroviruses In Pediatric Patients With Acute Respiratory Illness Before And During The Covid-19 Pandemic In The Us., Danielle A. Rankin, Andrew J. Spieker, Ariana Perez, Anna L. Stahl, Herdi K. Rahman, Laura S. Stewart, Jennifer E. Schuster, Joana Y. Lively, Zaid Haddadin, Varvara Probst, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Mary A. Staat, Elizabeth P. Schlaudecker, Monica M. Mcneal, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Susan I. Gerber, Meredith Mcmorrow, Brian Rha, James D. Chappell, Rangaraj Selvarangan, Claire M. Midgley, Natasha B. Halasa, Nvsn Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting.

OBJECTIVE: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought …

Monoclonal Antibody For The Prevention Of Respiratory Syncytial Virus In Infants And Children: A Systematic Review And Network Meta-Analysis, Mingyao Sun, Honghao Lai, Feiyang Na, Sheng Li, Xia Qiu, Jinhui Tian, Zhigang Zhang, Long Ge

Faculty, Staff and Student Publications

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.

OBJECTIVE: To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.

DATA SOURCES: In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.

STUDY SELECTION: Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, …

Safety And Tolerability Of Ser-109 As An Investigational Microbiome Therapeutic In Adults With Recurrent Clostridioides Difficile Infection: A Phase 3, Open-Label, Single-Arm Trial, Matthew D Sims, Sahil Khanna, Paul Feuerstadt, Thomas J Louie, Colleen R Kelly, Edward S Huang, Elizabeth L Hohmann, Elaine E L Wang, Caterina Oneto, Stuart H Cohen, Charles S Berenson, Louis Korman, Christine Lee, Bret Lashner, Colleen S Kraft, Mayur Ramesh, Michael Silverman, Darrell S Pardi, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke

Faculty, Staff and Student Publications

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR …

A Survey With Interventional Components Delivered On Tablet Devices Versus Usual Care To Increase Pre-Exposure Prophylaxis Uptake Among Cisgender Black Women: A Pilot Randomized Controlled Trial, Mandy J Hill, Angela M Heads, Robert Suchting, Angela L Stotts

Faculty, Staff and Student Publications

BACKGROUND: Cisgender (cis) Black women in the USA are more likely to become HIV positive during their lifetime than other women. We developed and implemented a behavioral intervention, Increasing PrEP (iPrEP), the first pilot randomized controlled trial (RCT) aimed at motivating cis Black women to be willing to use PrEP for HIV prevention and attend an initial PrEP clinic visit following an emergency department visit.

METHODS: Eligible participants were Black cisgender women ages 18-55 years who acknowledged recent condomless sex and substance use. Participants were randomized to iPrEP or usual care (UC). iPrEP is a survey-based intervention designed to raise …

Factors Associated With Prevalent Mycobacterium Tuberculosis Infection And Disease Among Adolescents And Adults Exposed To Rifampin-Resistant Tuberculosis In The Household, Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra De Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio Da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, Actg A5300/Impaact 2003 Phoenix Feasibility Study Team

Journal Articles: Infectious Diseases

BACKGROUND: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations.

METHODS: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated …

Hpv-Related Oropharyngeal Cancer Early Detection In Gay And Bisexual Men Is An “Orphan” Practice: A Qualitative Analysis Among Healthcare Providers, I Niles Zoschke, Sarah L Bennis, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene Flash, Michael W Ross

Faculty, Staff and Student Publications

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer.

Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences …