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Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla Jul 2022

Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla

Faculty, Staff and Students Publications

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up …


Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu Jul 2022

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …


Analysis Of An Antibiotic Stewardship Program For Asymptomatic Bacteriuria In The Veterans Affairs Health Care System, Larissa Grigoryan, Aanand D Naik, Paola Lichtenberger, Christopher J Graber, Payal K Patel, Dimitri M Drekonja, Timothy P Gauthier, Bhavarth Shukla, Anne E Sales, Sarah L Krein, John N Van, Laura M Dillon, Sylvia J Hysong, Jennifer R Kramer, Annette Walder, David Ramsey, Barbara W Trautner Jul 2022

Analysis Of An Antibiotic Stewardship Program For Asymptomatic Bacteriuria In The Veterans Affairs Health Care System, Larissa Grigoryan, Aanand D Naik, Paola Lichtenberger, Christopher J Graber, Payal K Patel, Dimitri M Drekonja, Timothy P Gauthier, Bhavarth Shukla, Anne E Sales, Sarah L Krein, John N Van, Laura M Dillon, Sylvia J Hysong, Jennifer R Kramer, Annette Walder, David Ramsey, Barbara W Trautner

Faculty, Staff and Students Publications

IMPORTANCE: Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited.

OBJECTIVE: To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB.

DESIGN, SETTING, AND PARTICIPANTS: This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect …


Monkeypox: A Contemporary Review For Healthcare Professionals, Boghuma K Titanji, Bryan Tegomoh, Saman Nematollahi, Michael Konomos, Prathit A Kulkarni Jul 2022

Monkeypox: A Contemporary Review For Healthcare Professionals, Boghuma K Titanji, Bryan Tegomoh, Saman Nematollahi, Michael Konomos, Prathit A Kulkarni

Faculty, Staff and Students Publications

The ongoing 2022 multicountry outbreak of monkeypox is the largest in history to occur outside of Africa. Monkeypox is an emerging zoonotic disease that for decades has been viewed as an infectious disease with significant epidemic potential because of the increasing occurrence of human outbreaks in recent years. As public health entities work to contain the current outbreak, healthcare professionals globally are aiming to become familiar with the various clinical presentations and management of this infection. We present in this review an updated overview of monkeypox for healthcare professionals in the context of the ongoing outbreaks around the world.


Physician Assistant Global Advancement Through The Use Of Medical Relief Organizations, Kara Crafts Pa-C, Sarah Mistrot Pa-C, Mary Henningsgaard Pa-C, Kaley Morris Pa-C, Tamarrah Oliver Pa-C, Kevin Tran Pa-C, Trevor Crafts Md Jun 2022

Physician Assistant Global Advancement Through The Use Of Medical Relief Organizations, Kara Crafts Pa-C, Sarah Mistrot Pa-C, Mary Henningsgaard Pa-C, Kaley Morris Pa-C, Tamarrah Oliver Pa-C, Kevin Tran Pa-C, Trevor Crafts Md

Journal of Nursing & Interprofessional Leadership in Quality & Safety

Objectives: The physician assistant (PA) model has been adopted by many nations to alleviate health care disparities. The objective of the project is to understand how medical relief organizations are utilizing physician assistants and contributing to the advancement of the career globally.

Methods: A search was conducted to create a list of all U.S. based medical relief organizations. An 18-question online survey was sent to 493 organizations that met inclusion criteria.

Results: Total response rate of the survey was 56.2%. 75.6% of organizations reported using PAs on their medical relief projects, and PAs were used in clinic/hospital/and operative settings.

Conclusions: …


Worsening Glycemia Increases The Odds Of Intermittent But Not Persistent Staphylococcus Aureus Nasal Carriage In Two Cohorts Of Mexican American Adults, Heather T Essigmann, Craig L Hanis, Stacia M Desantis, William B Perkison, David A Aguilar, Goo Jun, D Ashley Robinson, Eric L Brown Jun 2022

Worsening Glycemia Increases The Odds Of Intermittent But Not Persistent Staphylococcus Aureus Nasal Carriage In Two Cohorts Of Mexican American Adults, Heather T Essigmann, Craig L Hanis, Stacia M Desantis, William B Perkison, David A Aguilar, Goo Jun, D Ashley Robinson, Eric L Brown

Faculty, Staff and Student Publications

Numerous host and environmental factors contribute to persistent and intermittent nasal Staphylococcus aureus carriage in humans. The effects of worsening glycemia on the odds of S. aureus intermittent and persistent nasal carriage was established in two cohorts from an adult Mexican American population living in Starr County, Texas. The anterior nares were sampled at two time points and the presence of S. aureus determined by laboratory culture and


Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris Jun 2022

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …


Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease, Sandra Pritzkow Jun 2022

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease, Sandra Pritzkow

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …


Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group Jun 2022

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …


Biochemical, Biophysical, And Immunological Characterization Of Respiratory Secretions In Severe Sars-Cov-2 Infections, Michael J Kratochvil, Gernot Kaber, Sally Demirdjian, Pamela C Cai, Elizabeth B Burgener, Nadine Nagy, Graham L Barlow, Medeea Popescu, Mark R Nicolls, Michael G Ozawa, Donald P Regula, Ana E Pacheco-Navarro, Samuel Yang, Vinicio A De Jesus Perez, Harry Karmouty-Quintana, Andrew M Peters, Bihong Zhao, Maximilian L Buja, Pamela Y Johnson, Robert B Vernon, Thomas N Wight, Carlos E Milla, Angela J Rogers, Andrew J Spakowitz, Sarah C Heilshorn, Paul L Bollyky Jun 2022

Biochemical, Biophysical, And Immunological Characterization Of Respiratory Secretions In Severe Sars-Cov-2 Infections, Michael J Kratochvil, Gernot Kaber, Sally Demirdjian, Pamela C Cai, Elizabeth B Burgener, Nadine Nagy, Graham L Barlow, Medeea Popescu, Mark R Nicolls, Michael G Ozawa, Donald P Regula, Ana E Pacheco-Navarro, Samuel Yang, Vinicio A De Jesus Perez, Harry Karmouty-Quintana, Andrew M Peters, Bihong Zhao, Maximilian L Buja, Pamela Y Johnson, Robert B Vernon, Thomas N Wight, Carlos E Milla, Angela J Rogers, Andrew J Spakowitz, Sarah C Heilshorn, Paul L Bollyky

Faculty, Staff and Student Publications

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e., resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percentages of solids and protein content were greatly elevated in COVID-19 compared with heathy control samples and closely resembled levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) were major components of respiratory secretions in COVID-19 and were likewise abundant in cadaveric lung tissues from these …


Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto Jun 2022

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …


Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo Jun 2022

Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of


Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee Jun 2022

Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee

Faculty, Staff and Student Publications

Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal …


Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino Jun 2022

Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino

Faculty, Staff and Students Publications

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over …


Assessing The Established Competency Categories Of The Biosafety, Infection Prevention, And Public Health Professions: A Guide For Addressing Needed Professional Development Training For The Current And Next Pandemic, Robert J Emery, Scott J Patlovich, Kristin G King, John M Lowe, Janelle Rios Jun 2022

Assessing The Established Competency Categories Of The Biosafety, Infection Prevention, And Public Health Professions: A Guide For Addressing Needed Professional Development Training For The Current And Next Pandemic, Robert J Emery, Scott J Patlovich, Kristin G King, John M Lowe, Janelle Rios

Faculty, Staff and Student Publications

A recent series of widespread infectious disease outbreaks has highlighted commonalities and differences between three key professions that operate on the front lines of response in support of research and/or direct healthcare providers: biosafety, infection prevention, and public health. This assessment, which builds upon previous study by the authors, examines the stated professional competency categories for these three areas, highlighting similarities and differences. This assessment is important as these professions are being drawn together in an operational environment driven by the current pandemic and inevitably future disease outbreaks. Cross-training opportunities for the various professions are proposed.


Hiv Response Interventions That Integrate Hiv Molecular Cluster And Social Network Analysis: A Systematic Review, Daniel J Gore, Kellie Schueler, Santhoshini Ramani, Arno Uvin, Gregory Phillips, Moira Mcnulty, Kayo Fujimoto, John Schneider Jun 2022

Hiv Response Interventions That Integrate Hiv Molecular Cluster And Social Network Analysis: A Systematic Review, Daniel J Gore, Kellie Schueler, Santhoshini Ramani, Arno Uvin, Gregory Phillips, Moira Mcnulty, Kayo Fujimoto, John Schneider

Faculty, Staff and Student Publications

Due to improved efficiency and reduced cost of viral sequencing, molecular cluster analysis can be feasibly utilized alongside existing human immunodeficiency virus (HIV) prevention strategies. The goal of this paper is to elucidate how HIV molecular cluster and social network analyses are being integrated to implement HIV response interventions. We searched PubMed, Scopus, PsycINFO, and Cochrane Library databases for studies incorporating both HIV molecular cluster and social network data. We identified 32 articles that combined analyses of HIV molecular sequences and social or sexual networks. All studies were descriptive. Six studies described network interventions informed by molecular and social data …


Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara Jun 2022

Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara

Faculty, Staff and Student Publications

Purpose: Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.

Experimental design: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.

Results: PD-L1-positive tumors exhibited increased …


Long-Term Outcomes Among Adolescent And Young Adult Survivors Of Acute Leukemia: A Surveillance, Epidemiology, And End Results Analysis, Amy M Berkman, Clark R Andersen, Branko Cuglievan, David C Mccall, Philip J Lupo, Susan K Parsons, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Tapan M Kadia, J A Livingston, Michael E Roth Jun 2022

Long-Term Outcomes Among Adolescent And Young Adult Survivors Of Acute Leukemia: A Surveillance, Epidemiology, And End Results Analysis, Amy M Berkman, Clark R Andersen, Branko Cuglievan, David C Mccall, Philip J Lupo, Susan K Parsons, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Tapan M Kadia, J A Livingston, Michael E Roth

Faculty, Staff and Student Publications

Background: There is a growing population of adolescent and young adult (AYA, age 15-39 years) acute leukemia survivors in whom long-term mortality outcomes are largely unknown.

Methods: The current study utilized the Surveillance, Epidemiology, and End Results (SEER) registry to assess long-term outcomes of AYA acute leukemia 5-year survivors. The impact of diagnosis age, sex, race/ethnicity, socioeconomic status, and decade of diagnosis on long-term survival were assessed utilizing an accelerated failure time model.

Results: A total of 1,938 AYA acute lymphoblastic leukemia (ALL) and 2,350 AYA acute myeloid leukemia (AML) survivors diagnosed between 1980 and 2009 were included with a …


A Prospective Randomized Study Comparing Ceftolozane/Tazobactam To Standard Of Care In The Management Of Neutropenia And Fever In Patients With Hematological Malignancies, Anne-Marie Chaftari, Ray Hachem, Alexandre E Malek, Victor E Mulanovich, Ariel D Szvalb, Ying Jiang, Ying Yuan, Shahnoor Ali, Rita Deeba, Patrick Chaftari, Issam Raad Jun 2022

A Prospective Randomized Study Comparing Ceftolozane/Tazobactam To Standard Of Care In The Management Of Neutropenia And Fever In Patients With Hematological Malignancies, Anne-Marie Chaftari, Ray Hachem, Alexandre E Malek, Victor E Mulanovich, Ariel D Szvalb, Ying Jiang, Ying Yuan, Shahnoor Ali, Rita Deeba, Patrick Chaftari, Issam Raad

Faculty, Staff and Student Publications

Background: With increased use of antibiotics in high-risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial, we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard of care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies.

Methods: We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21-28), and late follow-up (LFU; days 35-42).

Results: We …


Comprehensive Characterization Of Tumor Immune Landscape Following Oncolytic Virotherapy By Single-Cell Rna Sequencing, Divya Ravirala, Guangsheng Pei, Zhongming Zhao, Xiaoliu Zhang Jun 2022

Comprehensive Characterization Of Tumor Immune Landscape Following Oncolytic Virotherapy By Single-Cell Rna Sequencing, Divya Ravirala, Guangsheng Pei, Zhongming Zhao, Xiaoliu Zhang

Faculty, Staff and Student Publications

An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated. We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME. We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors. We also applied CellChat to analyze the complex interactions among the infiltrated immune cells. …


Peripheral Blood Gene Expression Profiling Shows Predictive Significance For Response To Mycophenolate In Systemic Sclerosis-Related Interstitial Lung Disease, Shervin Assassi, Elizabeth R Volkmann, W Jim Zheng, Xuan Wang, Holly Wilhalme, Marka A Lyons, Michael D Roth, Donald P Tashkin Jun 2022

Peripheral Blood Gene Expression Profiling Shows Predictive Significance For Response To Mycophenolate In Systemic Sclerosis-Related Interstitial Lung Disease, Shervin Assassi, Elizabeth R Volkmann, W Jim Zheng, Xuan Wang, Holly Wilhalme, Marka A Lyons, Michael D Roth, Donald P Tashkin

Faculty, Staff and Student Publications

OBJECTIVES: To characterise the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc)-related interstitial lung disease (ILD).

METHODS: PBC RNA samples from baseline and 12-month visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, were investigated by global RNA sequencing. Joint models were created to examine the predictive significance of

RESULTS: 134 patients with SSc-ILD (CYC=69 and MMF=65) were investigated. CYC led to an upregulation of erythropoiesis, inflammation …


Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang Jun 2022

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …


Part I Antimicrobial Resistance: Bacterial Pathogens Of Dermatologic Significance And Implications Of Rising Resistance, Saira George, Fiorinda F Muhaj, Celine D Nguyen, Stephen K Tyring Jun 2022

Part I Antimicrobial Resistance: Bacterial Pathogens Of Dermatologic Significance And Implications Of Rising Resistance, Saira George, Fiorinda F Muhaj, Celine D Nguyen, Stephen K Tyring

Faculty, Staff and Student Publications

Although the COVID-19 pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance crisis. In dermatology, antibiotics are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of antimicrobial resistance and review resistance concerns related to dermatology-relevant bacterial …


Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán Jun 2022

Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán

Faculty, Staff and Student Publications

Background: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.

Methods: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.

Results: A total of 211 patients were included. Mean age was 35.6 years. …


Role Of The Chemokine System In Liver Fibrosis: A Narrative Review, Kyle L Poulsen, Christina K Cajigas-Du Ross, Jarod K Chaney, Laura E Nagy Jun 2022

Role Of The Chemokine System In Liver Fibrosis: A Narrative Review, Kyle L Poulsen, Christina K Cajigas-Du Ross, Jarod K Chaney, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Liver fibrosis is a disease with characteristics of an aberrant wound healing response. Fibrosis is commonly the end-stage for chronic liver diseases like alcohol-associated liver disease (ALD), metabolic-associated liver disease, viral hepatitis, and hepatic autoimmune disease. Innate immunity contributes to the progression of many diseases through multiple mechanisms including production of pro-inflammatory mediators, leukocyte infiltration and tissue injury. Chemokines and their receptors orchestrate accumulation and activation of immune cells in tissues and are associated with multiple liver diseases; however, much less is known about their potential roles in liver fibrosis. This is a narrative review of current …


Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, David R Boulware, Nathan C Bahr, Cornelius J Clancy, Thomas S Harrison, Carol A Kauffman, Thuy Le, Marisa H Miceli, Eleftherios Mylonakis, M Hong Nguyen, Luis Ostrosky-Zeichner, Thomas F Patterson, John R Perfect, Andrej Spec, Dimitrios P Kontoyiannis, Peter G Pappas Jun 2022

Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, David R Boulware, Nathan C Bahr, Cornelius J Clancy, Thomas S Harrison, Carol A Kauffman, Thuy Le, Marisa H Miceli, Eleftherios Mylonakis, M Hong Nguyen, Luis Ostrosky-Zeichner, Thomas F Patterson, John R Perfect, Andrej Spec, Dimitrios P Kontoyiannis, Peter G Pappas

Faculty, Staff and Student Publications

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these …


Discovery Of The First Lyticstaphylococcus Pseudintermedius/ Staphylococcus Aureus Polyvalent Bacteriophages, Haroldo Hernandez Santos, Justin Clark, Austen Terwilliger, Anthony Maresso Jun 2022

Discovery Of The First Lyticstaphylococcus Pseudintermedius/ Staphylococcus Aureus Polyvalent Bacteriophages, Haroldo Hernandez Santos, Justin Clark, Austen Terwilliger, Anthony Maresso

Faculty, Staff and Students Publications

Background:

There are no verified lytic Staphylococcus pseudintermedius phages in the literature and few temperate phage genomes in databases. S. pseudintermedius is an opportunistic zoonotic pathogen of great importance in veterinary and human medicine.

Materials and Methods:

We discovered phages against canine-derived S. pseudintermedius isolates by screening dog feces, hair, and skin swabs. Fourteen new phages were isolated and characterized by genomic analysis, transmission electron microscopy, and host range determination.

Results:

Three phages—DH2, DH5, and DS10, a phage K variant—were predicted lytic by sequencing, a designation supported by mitomycin C induction. All three are S. pseudintermedius and Staphylococcus aureus polyvalent …


Syphilis In The Esophagus, Ronan Allencherril, Paul Nicholls, Shilpa Jain, Robert Sealock, Priti Dangayach Jun 2022

Syphilis In The Esophagus, Ronan Allencherril, Paul Nicholls, Shilpa Jain, Robert Sealock, Priti Dangayach

Faculty, Staff and Students Publications

This report documents a unique case of syphilis with esophageal involvement. Such a presentation is exceedingly rare in the modern era, particularly among patients without human immunodeficiency virus. Most instances were documented in the 1900s and earlier. Our patient presented with months of odynophagia and recurrent oral lesions. He was found to have a sizeable esophageal ulcer on endoscopy, with biopsy confirming the diagnosis of syphilis. His symptoms quickly resolved with intramuscular penicillin. This case highlights the importance of keeping a broad differential for odynophagia and suspicious lesions, cutaneous or mucosal.


Social And Demographic Disparities In The Severity Of Multisystem Inflammatory Syndrome In Children, Fabio Savorgnan, Sebastian Acosta, Alexander Alali, Axel Moreira, Ananth Annapragada, Craig G Rusin, Saul Flores, Rohit S Loomba, Alvaro Moreira Jun 2022

Social And Demographic Disparities In The Severity Of Multisystem Inflammatory Syndrome In Children, Fabio Savorgnan, Sebastian Acosta, Alexander Alali, Axel Moreira, Ananth Annapragada, Craig G Rusin, Saul Flores, Rohit S Loomba, Alvaro Moreira

Faculty, Staff and Students Publications

Social constructs are known risk factors for multisystem inflammatory syndrome in children. A review of 206 patients demonstrated that children who were non-Hispanic Black, over the age of 12 years or living in a disadvantaged neighborhood associated with severe multisystem inflammatory syndrome in children (intensive care unit admission, intubation and/or vasopressor use).


Mucosal Immunology Of The Ocular Surface, Cintia S De Paiva, Anthony J St Leger, Rachel R Caspi Jun 2022

Mucosal Immunology Of The Ocular Surface, Cintia S De Paiva, Anthony J St Leger, Rachel R Caspi

Faculty, Staff and Students Publications

The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories. Dry eye, a dysfunction of the lacrimal glands and/or Meibomian glands, which can both cause, or arise from, sensory defects, including those caused …