Digital Commons Network^™

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Volker Kiessling, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …

Second Annual Research Symposium Program With Abstracts, Office Of Research Affairs, Boonshoft School Of Medicine

Boonshoft School of Medicine Research Symposium

The program booklet is a compilation of abstracts from oral and poster presentations at Wright State University's First Annual Boonshoft School of Medicine Medical Research Symposium held on April 13, 2023.

Psychosocial Interventions Among Patients With Cancer And Their Family Caregivers In The Sub-Saharan Region: A Systematic Review, Ting Guan, Yousef Qan’Ir, Jamie Conklin, Chifundo Colleta Zimba, Agatha Bula, Wongani Jumbo, Kondwani Wella, Patrick Mapulanga, Samuel A.M. Bingo, Evelyn Chilemba, Jennifer Haley, Nilda Peragallo Montano, Ashley Leak Bryant, Lixin Song

Social Work - All Scholarship

Cancer is becoming a public health issue in the Sub-Saharan Africa (SSA).

This systematic review aims to synthesise psychosocial interventions and

their effects on the health outcomes of adult cancer patients and their

family caregivers in SSA. We identified eligible publications in English

language from PubMed, Cumulative Index of Nursing and Allied Health

Literature Plus with Full Text, Embase, APA PsycInfo, Scopus, and

African Index Medicus databases. We included psychosocial

interventions targeted adult cancer patients/survivors or their family

caregivers in SSA. This review identified five psychosocial interventions

from six studies that support adult cancer patients and their family

caregivers in …

Low And Differential Polygenic Score Generalizability Among African Populations Due Largely To Genetic Diversity, Kristin Tsuo, Ying Wang, Rahul Gupta, Lethukuthula L Nkambule, Heather Zar, Dan J Stein, Eugene Kinyanda, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRSs) in simulations across Africa and in empirical data from South Africa, Uganda, and the United Kingdom to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South African individuals, we find that PRS accuracy is low for all traits but varies across …

Development Of A Corticosteroid-Immunosuppressed Mouse Model To Study The Pathogenesis And Therapy Of Influenza-Associated Pulmonary Aspergillosis, Sebastian Wurster, Jezreel Pantaleón García, Nathaniel D Albert, Ying Jiang, Keerthi Bhoda, Yongxing Wang, Scott Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, 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 …

Application Of A Novel Lytic Jerseyvirus Phage Lpsent1 For The Biological Control Of The Multidrug-Resistant Salmonella Enteritidis In Foods, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Khloud M. Algothmi, Ahmed Esmael

Nebraska Center for Virology: Faculty Publications

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including …

Internal Medicine Residency Newsletter, April 2023, Amani Khalouf, Amir Mahmoud, Anas M. Hashem

Rochester Regional Health authored publications and proceedings

A newsletter created by and for the Rochester General Hospital Internal Medicine Residency Program.

This issue:

1. A word from the PD
2. News & announcements
3. Resident corner
4. Awards and scholarship
5. Conferences and deadlines
6. Introducing IMRC
7. Article of the month
8. Community outreach activities
9. Happy birthday!
10. Crossword puzzle

The Sars-Cov-2 Utr’S Intrudes Host Rbp’S And Modulates Cellular Splicing, Anjali Singh, Kush Kumar Pandey, Shubham Kumar Agrawal, Rupesh K. Srivastava, Sankar Bhattacharyya, Bhupendra Verma

Nebraska Center for Virology: Faculty Publications

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of posttranscriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3’UTRs of the …

Pre-Transplant Evaluation Period Efficiency Through The Use Of An Electronic Scheduling Template, Christy Dawn Byrd

Student Scholarly Projects

Practice Problem: Candidacy for transplant evaluation is a complex and lengthy evaluation process. Delays in National Organ Registry have significant unfavorable impacts on patient outcomes as 22 people a day die awaiting a lifesaving treatment. Operational efficiencies can improve the pre-transplant evaluation period and significantly improve patient outcomes.

PICOT: In an outpatient transplant clinic (P), will leveraging an evidence-based scheduling template (I) compared to the current practice of first available appointment (C) reduce the evaluation period by 66% from a 3–4-week evaluation to a 1-week evaluation resulting in expedited listing on the National Organ Registry (O), when applied over …

Increases In Group A Streptococcal Infections In The Pediatric Population In Houston, Tx, 2022, Aya Aboulhosn, Misu A Sanson, Luis Alberto Vega, Maria G Segura, Lauren M Summer, J Chase Mcneil

Faculty, Staff and Student Publications

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.

Longitudinal Global Transcriptomic Profiling Of Preclinical Systemic Sclerosis Reveals Molecular Changes Associated With Disease Progression, Chiara Bellocchi, Lorenzo Beretta, Xuan Wang, Marka A Lyons, Maurizio Marchini, Vincenzo Carbonelli, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To investigate peripheral blood cell (PBCs) global gene expression profile of SSc at its preclinical stage (PreSSc) and to characterize the molecular changes associated with progression to a definite disease over time.

Material and methods: Clinical data and PBCs of 33 participants with PreSSc and 16 healthy controls (HCs) were collected at baseline and follow-up (mean 4.2 years). Global gene expression profiling was conducted by RNA sequencing and a modular analysis was performed.

Results: Comparison of baseline PreSSc to HCs revealed 2889 differentially expressed genes. Interferon signalling was the only activated pathway among top over-represented pathways. Moreover, 10 modules …

Increases In Group A Streptococcal Infections In The Pediatric Population In Houston, Tx, 2022, Lauren M Summer

Faculty, Staff and Student Publications

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.

A Comprehensive Review Of Covid-19: Associated Endocrine Manifestations, Saif Khan Md, Maryam Karim Mbbs, Vasu Gupta, Heenam Goel Md, Rohit Jain Md

Articles

Coronavirus disease 2019 (COVID-19) has played a significant part in systematic damage, affecting lives and leading to significant mortality. The endocrine system is one of the systems affected by this pandemic outbreak. The relationship between them has been identified in previous and ongoing research. The mechanism through which severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can achieve this is similar to that for organs that express angiotensin-converting enzyme 2 receptors, which is the primary binding site of the virus. Endocrine cells widely express angiotensin-converting enzyme 2 receptors and transmembrane serine protease 2, the primary mediators initiating the acute phase of the disease. …

Pediatric Malaria With Respiratory Distress: Prognostic Significance Of Point-Of-Care Lactate, Catherine Mitran, Robert Opoka, Andrea Conroy, Sophie Namasopo, Kevin Kain, Michael Hawkes

Paediatrics and Child Health, East Africa

Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed a pooled analysis of Ugandan children under five years of age hospitalized with malaria and RD from three past studies. In total, 1324 children with malaria and RD (median age 1.4 years, 46% female) from 21 health facilities were included. Median lactate level at admission was 4.6 mmol/L (IQR 2.6–8.5) and 586 patients (44%) had hyperlactatemia (lactate …

Berberine Disrupts Staphylococcal Proton Motive Force To Cause Potent Anti-Staphylococcal Effects, Neil Zhao, Selin Isguven, Rachel Evans, Thomas P Schaer, Noreen J. Hickok

Department of Orthopaedic Surgery Faculty Papers

The presence of antibiotic resistance has increased the urgency for more effective treatments of bacterial infections. Biofilm formation has complicated this issue as biofilm bacteria become tolerant to antibiotics due to environmental factors such as nutrient deprivation and adhesion. In septic arthritis, a disease with an 11% mortality rate, bacteria in synovial fluid organize into floating, protein-rich, bacterial aggregates (mm-cm) that display depressed metabolism and antibiotic tolerance. In this study, Staphylococcus aureus (S. aureus), which is the most common pathogen in septic arthritis, was tested against different inhibitors that modulate bacterial surface protein availability and that should decrease bacterial aggregation. …

2023 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2023 Annual Research Day conference.

Refugees Living With Dementia: Assessing The Barriers To Healthcare Access In Crisis-Affected Populations In Lebanon And Switzerland, And The Role Humanitarian Actors Have On Addressing Them, Pedro Gomez

Independent Study Project (ISP) Collection

As life expectancies increase in many places around the world, the prevalence of aging populations has increased. Consequently, increased numbers of people globally, especially in developing countries, have been diagnosed with conditions associated with old age. Dementia, a group of conditions associated with impaired cognitive functions, is among these. Notwithstanding, many developing countries have done poorly with regards to diagnosing and treating dementia, with some cultures not even having a word to describe the condition. (ADI 2022). The lack of a diagnosis and knowledge about dementia for some refugee communities has led to healthcare challenges in their host countries (Corfield …

The Effects Of Stigma Against Hiv And Tuberculosis On Patient Mental Health And Healthcare-Seeking Behavior In Dharamshala, Isabel Powell

Independent Study Project (ISP) Collection

HIV and tuberculosis are highly impactful diseases in India, causing severe morbidity, mortality, and suffering for millions. The stigmatization of these diseases unnecessarily exacerbates suffering for those afflicted and their families, compounding to the existing physical and emotional burden of diagnosis. Individual interviews with healthcare workers were conducted at Delek Hospital and the Tibetan Children’s Village in order to identify the existence and effects of stigma in the Tibetan refugee population in Dharamshala. Respondents reported an extremely high burden of tuberculosis in the community, complicated by the refugee status and unique infrastructural challenges of the population. The burden of HIV …

What Makes A Family: How An Empowerment-Based Health Care Delivery Model Employs Family Planning To Positively Impact Families In Rural Maharashtra: A Study In Jamkhed, Ahmadneger, Sezin Sakmar

Independent Study Project (ISP) Collection

The paper examines how an empowerment-based health care delivery model employs family planning services to positively impact families in rural Maharashtra. Family planning services provide those with the ability to become pregnant the option to control their own reproductive lives, whether they choose in favor of or against having children. Contraceptive use advances people’s human rights to choose whether they want to bear children and how many children they want, and people should have the choice of their preferred contraceptive method. The paper examines this issue within the framework of the Comprehensive Rural Health Project’s Jamkhed Model. Through the Jamkhed …

Outcomes Among Heart Failure Patients Hospitalized For Acute Pulmonary Embolism And Covid-19 Infection: Insight From The National Inpatient Sample, Bruce Adrian Casipit, Sahana Tito, Isaac Ogunmola, Abiodun Idowu, Shivaraj Patil, Kevin Lo, Behnam Bozorgnia

Einstein Health Papers

There is paucity of data regarding the outcomes of hospitalized acute pulmonary embolism (PE) patients with heart failure (HF) and Coronavirus Disease 2019 (COVID-19) infection. We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study to investigate the outcomes of hospitalized acute PE patients with HF and COVID-19, looking at its impact on in-hospital mortality, thrombolysis, and thrombectomy utilization as well as hospital length of stay (LOS). A total of 23,413 hospitalized acute PE patients with HF were identified in our study, of which 1.26% (n = 295/23,413) had COVID-19 infection. Utilizing a stepwise survey …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

Utilizing The System Engineering Trade Study Analysis Method To Analyze Patient Aeromedical Evacuation, Sara Shaghaghi, Jeremy M. Slagley, Michael E. Miller, Gaiven Varshney

Faculty Publications

The US Air Force has gone through many aeromedical patient isolation transport system designs. The first designs were developed in response to the Ebola outbreak in 2014 and, more recently, the COVID-19 pandemic. The trade study analysis part of the system engineering design method was used to analyze the historic and current aeromedical patient contamination control transport systems. A trade study is a process that evaluates alternatives based upon various “-ilities”, such as reconfigurability, flexibility, durability, cost, and more, and performs a systematic analysis to aid designers in producing a ‘good’ design alternative given the large set of possible solutions. …

Accuracy Of Therapeutic Drug Monitoring In Vancomycin And The Pharmacist Role: A Retrospective Case-Series, Kateryna Parkhomenko

Senior Theses

Vancomycin is a mainstay of therapy for treating virulent and resistant infections, especially methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin requires therapeutic drug monitoring (TDM) for optimal dosing and treatment. This requires pharmacists to calculate a dosing regimen that correlates to appropriate goal vancomycin concentrations in the blood. Dosing vancomycin can be difficult, as it varies on a patient’s weight, renal function, age, etc. Doses may have to be adjusted in response to out-of-range concentrations, which requires further pharmacy calculations. Inaccurate dosing poses a risk to patient safety and places a resource and time burden on pharmacists. If vancomycin dosing methods …

In Vitro Activity Of Eravacycline And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Kenneth Rolston, Bahgat Gerges, Lior Nesher, Samuel A Shelburne, Randall Prince

Faculty, Staff and Student Publications

BACKGROUND: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.

OBJECTIVES: We evaluated the

METHODS: Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.

RESULTS: Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were …

Letter To The Editor: Quality Criteria For Computational Models Predicting Individual Outcomes In Car-T Cell Therapy, Anna M Mc Laughlin, Cassian Yee

Faculty, Staff and Student Publications

No abstract provided.

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Veronica Brady, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

The In Vitro Activity Of Delafloxacin And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Bahgat Gerges, Kenneth Rolston, Samuel A Shelburne, Joel Rosenblatt, Randall Prince

Faculty, Staff and Student Publications

BACKGROUND: Fluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the

METHODS: Antimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.

RESULTS: Delafloxacin was more active than ciprofloxacin and levofloxacin against

CONCLUSIONS: Delafloxacin is more active than ciprofloxacin and levofloxacin against

A Non-Antibiotic-Disrupted Gut Microbiome Is Associated With Clinical Responses To Cd19-Car-T Cell Cancer Immunotherapy, Christoph K Stein-Thoeringer, Neeraj Y Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Matthias A Fante, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Raphael E Steiner, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Michael L Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Müller-Tidow, Frederick L Locke, Marco L Davila, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Hendrik Poeck, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Michael D Jain, Robert R Jenq, Eran Elinav

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals …