Digital Commons Network^™

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

T Cell Fate Decisions During Memory Cell Generation With Aging, Ines Sturmlechner, Abhinav Jain, Yunmei Mu, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

The defense against infectious diseases, either through natural immunity or after vaccinations, relies on the generation and maintenance of protective T cell memory. Naïve T cells are at the center of memory T cell generation during primary responses. Upon activation, they undergo a complex, highly regulated differentiation process towards different functional states. Naïve T cells maintained into older age have undergone epigenetic adaptations that influence their fate decisions during differentiation. We review age-sensitive, molecular pathways and gene regulatory networks that bias naïve T cell differentiation towards effector cell generation at the expense of memory and Tfh cells. As a result, …

Microfluidic Paper-Based Device Coupled With 3d Printed Imaging Box For Colorimetric Detection In Resource-Limited Settings, Vijay Vaishampayan, Oinam Robita Chanu, Balasubramanian Sivasamy, Muthamilselvi Ponnuchamy, Varshini Karthik, Ambar Pendharkar, Lohith Srinivas Thotakura, Aryan Prabhu, Venkatesan Dhananjeyan, Ashish Kapoor

Faculty, Staff and Student Publications

Rapid and effective methods for the detection of analytes such as water contaminants, food adulterants and biomolecules are essential for the protection of public health and environmental protection. Most of the currently established analytical techniques need sophisticated equipment, centralized testing facilities, costly operations, and trained personnel. Such limitations make them inaccessible to the general populace, particularly in regions with limited resources. The emergence of microfluidic devices offers a promising alternative to overcome several such constraints. This work describes a protocol for fabricating a low-cost, open-source paper-based microfluidic device using easily available tools and materials for colorimetric detection of analytes. The …

Making Waves: Integrating Wastewater Surveillance With Dynamic Modeling To Track And Predict Viral Outbreaks, Tin Phan, Samantha Brozak, Bruce Pell, Jeremiah Oghuan, Anna Gitter, Tao Hu, Ruy M Ribeiro, Ruian Ke, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Wastewater surveillance has proved to be a valuable tool to track the COVID-19 pandemic. However, most studies using wastewater surveillance data revolve around establishing correlations and lead time relative to reported case data. In this perspective, we advocate for the integration of wastewater surveillance data with dynamic within-host and between-host models to better understand, monitor, and predict viral disease outbreaks. Dynamic models overcome emblematic difficulties of using wastewater surveillance data such as establishing the temporal viral shedding profile. Complementarily, wastewater surveillance data bypasses the issues of time lag and underreporting in clinical case report data, thus enhancing the utility and …

Lymphocytic Choriomeningitis Virus In Person Living With Hiv, Connecticut, Usa, 2021, Jonathan Dyal, Shiv Gandhi, Caitlin M Cossaboom, Austin Leach, Ketan Patel, Marjorie Golden, Joseph Canterino, Marie-Louise Landry, Debi Cannon, Mary Choi, Inna Krapiunaya, John D Klena, Trevor Shoemaker

Faculty, Staff and Student Publications

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

Rare Case Of Pediatric Post-Transplant Lymphoproliferative Disorder Presenting With Pleural Masses Complicated By Pleural Effusions, Erini Nessim Kostandy, David Wan, Essam Imseis

Faculty, Staff and Student Publications

Post-transplant lymphoproliferative disorder is a complication in organ transplant recipients characterized by uncontrolled proliferation of B-lymphocytes, occurring in 6% of pediatric patients, with risk factors including primary Epstein-Barr virus infection, intensity of immunosuppression, and cytomegalovirus infection. The clinical symptoms are often nonspecific, and it is associated with a high mortality rate if left untreated. We describe a rare case of post-transplant lymphoproliferative disorder who presented with pleural-based masses resulting in pleural effusions.

Monkeypox Presenting As A Hand Consult In The Emergency Department: Two Case Reports, David T Mitchell, James A Mentz, Yuewei Wu-Fienberg, Wendy Chen, Matthew R Greives, Erik S Marques

Faculty, Staff and Student Publications

The ongoing outbreak of the monkeypox virus (now referred to as "mpox") was deemed a public health emergency by the World Health Organization in 2022. The United States now reports the highest number of mpox cases, with 29 980 cases and 21 deaths as of January 11, 2023. The most common presenting symptom is a pruritic, vesicular rash that commonly involves the hands. While covering hand call, our division has encountered 2 cases of mpox in the emergency department for which the chief complaint was a hand lesion. Because hand surgeons will be called upon to make an initial diagnosis, …

Top Ten Tips Palliative Care Clinicians Should Know About Working With Adults Receiving Extracorporeal Membrane Oxygenation, Astrid Grouls, Krista Dobbie, Kathleen Neuendorf, Shunichi Nakagawa, Alisha Young, William E Rosa, Bindu Akkanti

Faculty, Staff and Student Publications

Extracorporeal membrane oxygenation (ECMO) is an invasive intervention that is both resource- and labor-intensive. It can also be emotionally challenging for all involved. Palliative care (PC) clinicians can support adult patients, families, surrogate decision makers, and the interdisciplinary team (IDT) throughout ECMO, starting at the time of ECMO initiation through discontinuation and to bereavement in the event of a patient's death. In addition to knowing the basics of ECMO circuitry, indications to start ECMO, and the complex decision points throughout treatment, PC clinicians must understand the critical need for specialist and IDT coordination when discussing prognosis and resuscitation, clarifying goals …

Reduced Digestion Of Circulating Genomic Dna In Systemic Sclerosis Patients With The Dnase1l3 R206c Variant\, Brian Skaug, Xinjian Guo, Yuanteng Jeff Li, Julio Charles, Kay T Pham, Jacob Couturier, Dorothy E Lewis, Claudia Bracaglia, Ivan Caiello, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: Polymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs).

Methods: The ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected …

Interstitial Lung Abnormalities After Hospitalization For Covid-19 In Patients With Cancer: A Prospective Cohort Study, Sungryong Noh, Christopher Bertini, Isabel Mira-Avendano, Maryam Kaous, Bela Patel, Saadia A Faiz, Vickie R Shannon, Diwakar D Balachandran, Lara Bashoura, Roberto Adachi, Scott E Evans, Burton Dickey, Carol Wu, Girish S Shroff, Joanna-Grace Manzano, Bruno Granwehr, Shannon Holloway, Kodwo Dickson, Alyssa Mohammed, Mayoora Muthu, Hui Song, Caroline Chung, Jia Wu, Lyndon Lee, Ying Jiang, Fareed Khawaja, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients.

METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and …

Alliance For Innovation On Maternal Health: Consensus Bundle On Sepsis In Obstetric Care., Melissa E Bauer, Catherine Albright, Malavika Prabhu, R Phillips Heine, Chelsea Lennox, Christie Allen, Carol Burke, April Chavez, Brenna L Hughes, Susan Kendig, Maile Le Boeuf, Elliott Main, Tiffany Messerall, Luis D Pacheco, Laura Riley, Rachel Solnick, Andrew Youmans, Ronald Gibbs

Women’s Health Articles

Sepsis in obstetric care is one of the leading causes of maternal death in the United States, with Black, Asian/Pacific Islander, and American Indian/Alaska Native obstetric patients experiencing sepsis at disproportionately higher rates. State maternal mortality review committees have determined that deaths are preventable much of the time and are caused by delays in recognition, treatment, and escalation of care. The "Sepsis in Obstetric Care" patient safety bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people by preventing infection and recognizing and treating infection early to prevent progression to sepsis. This is …

Antimicrobial Mitochondrial Reactive Oxygen Species Induction By Lung Epithelial Immunometabolic Modulation, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleón García, Miguel M Leiva-Juárez, David L Goldblatt, Fahad Gulraiz, Lisandra Vila Ellis, Jichao Chen, Michael K Longmire, Sri Ramya Donepudi, Philip L Lorenzi, Hao Wang, Lee-Jun Wong, Michael J Tuvim, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs' intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in …

Rapidly Progressing Autoimmune Hemolytic Anemia In A Pediatric Patient With Covid-19., Julia E. Kononowicz, M. Farhan Ali, William Palko, Sean Pyper, Nisha Agasthya

Manuscripts, Articles, Book Chapters and Other Papers

SARS-CoV-2 is a novel virus that is known to have a predilection for complications associated with the respiratory system. Although COVID-19 has a wide spectrum of manifestations, the pathophysiology of severe illness remains poorly understood but is thought to be associated with fulminant cytokine release. While severe complications secondary to COVID-19 in the pediatric population are considered rare, they do happen. Children with and without comorbidities have required intensive care unit admissions for respiratory distress and, more notably, multisystem inflammatory syndrome in children (MIS-C). While MIS-C is associated with hematologic complications, such as thrombocytopenia and coagulopathies, it is not associated …

Diversity, Equity, And Inclusion In The Melanoma Research Community, Marie E Portuallo, David Y Lu, Gretchen M Alicea, Joel Bolling, Rebecca Lee, Jennifer Mcquade, Allison Betof Warner, Michael Davies, Ashani Weeraratna, Jessie Villanueva, Vito W Rebecca

Faculty, Staff and Student Publications

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant …

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Rebecca M Legere, Angelica R Allegro, Yvonne Affram, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …

New Records Of Ornithodoros Turicata (Ixodida: Argasidae) In Rural And Urban Sites In The Mexican States Of Aguascalientes And Zacatecas Indicate The Potential For Tick-Borne Relapsing Fever, Edwin Vázquez-Guerrero, José Luis González-Quiroz, María Lilia Domínguez-López, Alexander R Kneubehl, Aparna Krishnavajhala, Michael W Curtis, Alejandro Ponce-Mendoza, Paulina Estrada-De Los Santos, Job E Lopez, J Antonio Ibarra

Faculty, Staff and Students Publications

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. …

Transfusion Reactions Associated With Covid-19 Convalescent Plasma In Outpatient Clinical Trials, Moises A Huaman, Jay S Raval, James H Paxton, Giselle S Mosnaim, Bela Patel, Shweta Anjan, Barry R Meisenberg, Adam C Levine, Christi E Marshall, Anusha Yarava, Aarthi G Shenoy, Sonya L Heath, Judith S Currier, Yuriko Fukuta, Janis E Blair, Emily S Spivak, Joann R Petrini, Patrick B Broderick, William Rausch, Marieelena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Seble G Kassaye, Malathi Ram, Ying Wang, Piyali Das, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Daniel E Ford, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, Stephan Ehrhardt, Bryan Lau, Sheriza N Baksh, David M Shade, Arturo Casadevall, Daniel F Hanley, Jiangda Ou, Thomas J Gniadek, Alyssa Ziman, Shmuel Shoham, Kelly A Gebo, Evan M Bloch, Aaron A R Tobian, David J Sullivan, Jonathan M Gerber

Faculty, Staff and Students Publications

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.

RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 …

Myths And Methodologies: Cardiopulmonary Exercise Testing For Surgical Risk Stratification In Patients With An Abdominal Aortic Aneurysm; Balancing Risk Over Benefit, Damian M Bailey, Richard G Davies, George A Rose, Michael H Lewis, Ahmed Abd Aldayem, Chistopher P Twine, Wael Awad, Matti Jubouri, Idhrees Mohammed, Carlos A Mestres, Edward P Chen, Joseph S Coselli, Ian M Williams, Mohamad Bashir, International Academic Surgical Consortium (Thalamus)

Faculty, Staff and Students Publications

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring …

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

An Unusual Presentation Of Infective Endocarditis, Ethan J. Peterson, Jordan Jackson, Syed M. Zaidi, Jorge Perez

HCA Healthcare Journal of Medicine

Introduction

Leukocytoclastic vasculitis is the inflammation of small blood vessels due to leukocyte migration that comprises a wide range of differentials. It can be caused by autoimmune disorders, infections, neoplasms, or certain medications and warrants prompt recognition and therapy for optimal patient outcomes.

Case Presentation

Here we present a case of a 37-year-old male who presented with a painful, petechial rash on his torso and extremities. Skin biopsy revealed leukocytoclastic vasculitis, thereby prompting a comprehensive investigation into the underlying etiology leading to the diagnosis of Pseudomonas aeruginosa infective endocarditis.

Conclusion

Pseudomonas aeruginosa is a rare cause of infective endocarditis with …

Covid-19 Disease Characterization And Outcomes Comparison In Pediatrics, Rachel Rowland, Abigail Schauble, Brendon Cornett

HCA Healthcare Journal of Medicine

Background

It has been reported that children experience less severe COVID-19 symptoms than adults; however, the literature that supports this idea is evolving. The purpose of this study was to retrospectively characterize hospitalized COVID-19-positive pediatric patients with a focus on the assessment of risk factors for poorer outcomes, mortality, and evaluation of interventions utilized and associated clinical outcomes.

Methods

We conducted a multi-center retrospective chart review of patients 18 years old or younger who were COVID-19 positive and admitted to any US HCA Healthcare Pediatric service line between January 1, 2020, and November 30, 2020. We identified 6081 children across …

Loss Of Stearoyl-Coa Desaturase 2 Disrupts Inflammatory Response In Macrophages, Joseph B Lin, Amy Mora, Tzu Jui Wang, Andrea Santeford, Darksha Usmani, Marianne M Ligon, Indira U Mysorekar, Rajendra S Apte

Faculty, Staff and Students Publications

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of

Isolated Cerebral Mucormycosis And Aspergillosis Coinfection In An Immunocompromised Adult, George Sun, Allison Weiss, Joy Zhao, Mitchell Silver, Michael Demaio, Sara Dehbashi

Department of Neurology Faculty Papers

Opportunistic fungal infections are a major cause of mortality in immunosuppressed patients, with mucormycosis and aspergillosis as two of the most commonly identified fungal organisms. Coinfection with mucormycosis and aspergillosis is rare, but cases have been reported in literature, most commonly presenting as disseminated invasive fungal infection with cerebrorhino-orbital involvement in an immunocompromised patient. Infections are most commonly caused by direct implantation of spores with localised angioinvasion. Haematogenous spread is rare, with most cases secondary to haematological malignancies or intravenous drug use. Coinfection with mucormycosis and aspergillosis portends a poor prognosis, with a high mortality rate. Thus, prompt recognition and …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Temporal Dynamics Of Genetically Heterogeneous Extended-Spectrum Cephalosporin-Resistant Escherichia Coli Bloodstream Infections, William C Shropshire, Benjamin Strope, Selvalakshmi Selvaraj Anand, Jordan Bremer, Patrick Mcdaneld, Micah M Bhatti, Anthony R Flores, Awdhesh Kalia, Samuel A Shelburne

Faculty, Staff and Student Publications

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. …

Exploration Of A Potential Desirability Of Outcome Ranking Endpoint For Complicated Intra-Abdominal Infections Using 9 Registrational Trials For Antibacterial Drugs, Tori Kinamon, Ramya Gopinath, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Sumati Nambiar, Peter Kim, Helen W Boucher

Faculty, Staff and Student Publications

BACKGROUND: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI).

METHODS: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we …

Antibiotic Use Without A Prescription: A Multisite Survey Of Patient, Health System, And Encounter Characteristics, Larissa Grigoryan, Michael K Paasche-Orlow, Osvaldo Alquicira, Lindsey Laytner, Matthew Schlueter, Richard L Street, Juanita Salinas, Kenneth Barning, Hammad Mahmood, Thomas W Porter, Fareed Khan, Jean L Raphael, Fabrizia Faustinella, Barbara W Trautner

Faculty, Staff and Students Publications

Background: Using antibiotics without a prescription is potentially unsafe and may increase the risk of antimicrobial resistance. We evaluated the effect of patient, health system, and clinical encounter factors on intention to use antibiotics without a prescription that were (1) purchased in the United States, (2) obtained from friends or relatives, (3) purchased abroad, or (4) from any of these sources.

Methods: The survey was performed January 2020-June 2021 in 6 publicly funded primary care clinics and 2 private emergency departments in Texas, United States. Participants included adult patients visiting 1 of the clinical settings. Nonprescription use was defined as …

Effects Of Surface Treatment Method Forming New Nano/Micro Hierarchical Structures On Attachment And Proliferation Of Osteoblast-Like Cells, Jae-Seung Im, Hyunsuk Choi, Hyun-Wook An, Tae-Yub Kwon, Min-Ho Hong

Faculty, Staff and Student Publications

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution-a hydrogen peroxide-sodium bicarbonate mixture-on the surface properties and contact angles of osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. …

Multiomic Investigations Into Lung Health And Disease, Sarah E Blutt, Cristian Coarfa, Josef Neu, Mohan Pammi

Faculty, Staff and Students Publications

Diseases of the lung account for more than 5 million deaths worldwide and are a healthcare burden. Improving clinical outcomes, including mortality and quality of life, involves a holistic understanding of the disease, which can be provided by the integration of lung multi-omics data. An enhanced understanding of comprehensive multiomic datasets provides opportunities to leverage those datasets to inform the treatment and prevention of lung diseases by classifying severity, prognostication, and discovery of biomarkers. The main objective of this review is to summarize the use of multiomics investigations in lung disease, including multiomics integration and the use of machine learning …