Digital Commons Network^™

Central Nervous System Intravascular Lymphoma Leading To Rapidly Progressive Dementia, Christie G Turin, Kevin Ting, Anthony Bradshaw, S Richard Dunham, Karen Nunez-Wallace, Shital M Patel, Priti Dangayach, Stephanie Holdener, Weei-Chin Lin

Faculty, Staff and Students Publications

Intravascular lymphoma is an uncommon subtype of B-cell lymphoma with neoplastic cells limited to the lumen of small blood vessels. We report a case of a 52-year-old man who presented with constitutional symptoms and rapidly progressive dementia. He was found to have diffuse leptomeningeal and faint parenchymal enhancement on magnetic resonance imaging and was subsequently diagnosed with intravascular lymphoma following a brain biopsy. He responded remarkably well to systemic and intrathecal chemotherapy. The diagnosis and treatment of intravascular lymphoma have been guided by a few case reports and are largely based on expert opinion.

Plasmid-Based Reverse Genetics For Probing Phosphorylation-Dependent Viroplasm Formation In Rotaviruses, Jeanette M Criglar, Sue E Crawford, Mary K Estes

Faculty, Staff and Students Publications

Rotavirus (RV) replication occurs in cytoplasmic compartments, known as viroplasms, that are composed of viral and cellular proteins. Viroplasm formation requires RV nonstructural proteins NSP2 and NSP5 and cellular lipid droplets (LDs); however, the mechanisms required for viroplasm assembly remain largely unknown. We previously identified two conformationally-distinct forms of NSP2 (dNSP2, vNSP2) found in RV-infected cells that interact differentially with hypo- and hyperphosphorylated NSP5, respectively, and indicate a coordinated phosphorylation-dependent mechanism regulating viroplasm assembly. We also reported that phosphorylation of dNSP2 on serine 313 by the cellular kinase CK1α triggers the localization of vNSP2 to sites of viroplasm assembly and …

Protein-Functionalized Poly(Ethylene Glycol) Hydrogels As Scaffolds For Monolayer Organoid Culture, Reid L Wilson, Ganesh Swaminathan, Khalil Ettayebi, Carolyn Bomidi, Xi-Lei Zeng, Sarah E Blutt, Mary K Estes, K Jane Grande-Allen

Faculty, Staff and Students Publications

Stem cell-derived, organotypic in vitro models, known as organoids, have emerged as superior alternatives to traditional cell culture models due to their unparalleled ability to recreate complex physiological and pathophysiological processes. For this reason, they are attractive targets of tissue-engineering efforts, as constructs that include organoid technology would be expected to better simulate the many functions of the desired tissue or organ. While the 3D spheroidal architecture that is the default architecture of most organoid models may be preferred for some applications, 2D monolayer arrangements remain the preferred organization for many applications in tissue engineering. Therefore, in this work, we …

Helicobacter Pylori Diagnosis And Therapy In The Era Of Antimicrobial Stewardship, Akiko Shiotani, Priya Roy, Hong Lu, David Y Graham

Faculty, Staff and Students Publications

The diagnosis and therapy of Helicobacter pylori infection have undergone major changes based on the use the principles of antimicrobial stewardship and increased availability of susceptibility profiling. H. pylori gastritis now recognized as an infectious disease, as such there is no placebo response allowing outcome to be assessed in relation to the theoretically obtainable cure rate of 100%. The recent recognition of H. pylori as an infectious disease has changed the focus to therapies optimized to reliably achieve high cure rates. Increasing antimicrobial resistance has also led to restriction of clarithromycin, levofloxacin, or metronidazole to susceptibility-based therapies. Covid-19 resulted in …

Safety And Efficacy Of Fecal Microbiota Transplantation To Treat And Prevent Recurrent Clostridioides Difficile In Cancer Patients, Hiba Ali, Shruti Khurana, Weijie Ma, Yuanzun Peng, Zhi-Dong Jiang, Herbert Dupont, Hao Chi Zhang, Anusha S Thomas, Pablo Okhuysen, Yinghong Wang

Faculty, Staff and Students Publications

Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center.

Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline …

Alpha-Single Chains Of Collagen Type Vi Inhibit The Fibrogenic Effects Of Triple Helical Collagen Vi In Hepatic Stellate Cells, Christian Freise, Hyunho Lee, Christopher Chronowski, Doug Chan, Jessica Cziomer, Martin Rühl, Tarkan Dagdelen, Maik Lösekann, Ulrike Erben, Andre Catic, Werner Tegge, Detlef Schuppan, Rajan Somasundaram, Ergun Sahin

Faculty, Staff and Students Publications

The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat …

Open Problems In Extracellular Rna Data Analysis: Insights From An Ercc Online Workshop, Roger P Alexander, Robert R Kitchen, Juan Pablo Tosar, Matthew Roth, Pieter Mestdagh, Klaas E A Max, Joel Rozowsky, Karolina Elżbieta Kaczor-Urbanowicz, Justin Chang, Leonora Balaj, Bojan Losic, Eric L Van Nostrand, Emily Laplante, Bogdan Mateescu, Brian S White, Rongshan Yu, Aleksander Milosavljevic, Gustavo Stolovitzky, Ryan M Spengler

Faculty, Staff and Students Publications

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19–20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Wanda Phipatanakul, David T Mauger, Theresa W Guilbert, Leonard B Bacharier, Sandy Durrani, Daniel J Jackson, Fernando D Martinez, Anne M Fitzpatrick, Amparito Cunningham, Susan Kunselman, Lisa M Wheatley, Cindy Bauer, Carla M Davis, Bob Geng, Kirsten M Kloepfer, Craig Lapin, Andrew H Liu, Jacqueline A Pongracic, Stephen J Teach, James Chmiel, Jonathan M Gaffin, Matthew Greenhawt, Meera R Gupta, Peggy S Lai, Robert F Lemanske, Wayne J Morgan, William J Sheehan, Jeffrey Stokes, Peter S Thorne, Hans C Oettgen, Elliot Israel

Faculty, Staff and Students Publications

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In …

Spinal Cord Injury Provider Knowledge And Attitudes Toward Bacteriuria Management And Antibiotic Stewardship, Felicia Skelton, Sarah May, Larissa Grigoryan, Ivy Poon, Sally Ann Holmes, Lindsey Martin, Barbara W Trautner

Faculty, Staff and Students Publications

INTRODUCTION: Bacteriuria, either asymptomatic or urinary tract infection, is common in persons with spinal cord injury or disorder (SCI/D). In the Veterans Health Administration (VHA), conflicting clinical practice guidelines make appropriate bacteriuria management and antibiotic stewardship challenging.

OBJECTIVE: To explore SCI/D provider knowledge, attitudes, and teamwork around bacteriuria management during the VHA SCI/D annual examination.

DESIGN: Mixed methods.

SETTING: VHA SCI/D centers.

PARTICIPANTS: SCI/D staff providers and physical medicine and rehabilitation resident physicians.

MAIN OUTCOME MEASUREMENTS: Knowledge, safety, and teamwork scores on bacteriuria management using a validated questionnaire. Themes on barriers and facilitators to bacteriuria management during the SCI/D annual …

Postacute Covid-19: An Overview And Approach To Classification, Eva M Amenta, Amy Spallone, Maria C Rodriguez-Barradas, Hana M El Sahly, Robert L Atmar, Prathit A Kulkarni

Faculty, Staff and Students Publications

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other …

Organizational Readiness Assessment In Acute And Long-Term Care Has Important Implications For Antibiotic Stewardship For Asymptomatic Bacteriuria, Melanie C Goebel, Barbara W Trautner, Yiqun Wang, John N Van, Laura M Dillon, Payal K Patel, Dimitri M Drekonja, Christopher J Graber, Bhavarth S Shukla, Paola Lichtenberger, Christian D Helfrich, Anne Sales, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment.

METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale.

RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was …

Donor And Transplant Candidate Selection For Solid Organ Transplantation During The Covid-19 Pandemic, N Thao N Galvan, Nicolas F Moreno, Jay E Garza, Susan Bourgeois, Marion Hemmersbach-Miller, Bhamidipati Murthy, Katherine Timmins, Christine A O'Mahony, James Anton, Andrew Civitello, Puneet Garcha, Gabe Loor, Kenneth Liao, Alexis Shaffi, John Vierling, Rise Stribling, Abbas Rana, John A Goss

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating …

Chronic Ulcers And Malnutrition In An African Patient\, Timothy G Singer, Monica A Bray, Audrey Chan, Saki Ikeda, Brittany Walters, Maren Y Fuller, Carla Falco

Faculty, Staff and Students Publications

An 11-year-old female with a congenitally malformed left hand, sickle-cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared following trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months prior to transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous (IV) antibiotics and close management by a Pediatric Infectious Disease specialist working for a non-governmental organization (NGO) in …

A Case Of Streptococcal Surgical Site Infection Following Mohs Surgery, Kami B Lowery, John J Kohorst, C Helen Malone, Ikue Shimizu

Faculty, Staff and Students Publications

Group A β-hemolytic Streptococcal (GAS) cellulitis is an uncommon surgical site infection that presents with rapid onset of pain and swelling in the first few days after a procedure. Unlike staphylococcal cellulitis, GAS cellulitis lacks purulence and spreading erythema. The absence of these classic signs may delay the diagnosis of GAS cellulitis and lead to severe complications. We present the case of an immunosuppressed 49-year-old patient who developed swelling and severe pain at his incision site two days after undergoing Mohs micrographic surgery on his forehead. He was clinically diagnosed with GAS cellulitis and recovered with intravenous antibiotics. Unfortunately, there …

Validating Use Of Electronic Health Data To Identify Patients With Urinary Tract Infections In Outpatient Settings, George Germanos, Patrick Light, Roger Zoorob, Jason Salemi, Fareed Khan, Michael Hansen, Kalpana Gupta, Barbara Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

OBJECTIVE: To validate the use of electronic algorithms based on International Classification of Diseases (ICD)-10 codes to identify outpatient visits for urinary tract infections (UTI), one of the most common reasons for antibiotic prescriptions.

METHODS: ICD-10 symptom codes (e.g., dysuria) alone or in addition to UTI diagnosis codes plus prescription of a UTI-relevant antibiotic were used to identify outpatient UTI visits. Chart review (gold standard) was performed by two reviewers to confirm diagnosis of UTI. The positive predictive value (PPV) that the visit was for UTI (based on chart review) was calculated for three different ICD-10 code algorithms using (1) …

A Survey Of Dermatology Residents And Program Directors Assessing The Transition To Dermatology Residency, Christina Hopkins, Omid Jalali, Danielle Guffey, Harry Dao

Faculty, Staff and Students Publications

The transition from internship to residency is a critical period for trainees. This study investigated factors that influence the transition of residents from postgraduate year 1 (PGY-1) to dermatology residency. In June 2019, a program director–specific survey and a resident-oriented survey were administered via Survey Monkey. An email containing survey hyperlinks was sent via the Association of Professors of Dermatology Listserv to program directors, who were asked to forward the email to their current trainees. A total of 44 dermatology residents and 33 program directors responded. More than 58% of program directors identified a preliminary year in internal medicine as …

Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon

Faculty, Staff and Students Publications

INTRODUCTION: There is a need for a standardized approach to understand and assess clinical reasoning in medical learners. The Assessment of Reasoning Tool was developed based on prevalent theories and frameworks using a multidisciplinary expert panel. As the tool provides a standardized rubric for assessing clinical reasoning, we designed an interactive train-the-trainer workshop for clinical educators and education leaders interested in improving their teaching skills and/or introducing curricula surrounding diagnostic reasoning.

METHODS: In this workshop, participants were exposed to the major domains of diagnostic reasoning and how to apply it to the assessment of a learner's skills. Kolb's experiential learning …

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Low Yield Of Hepatitis C Infection In An Outreach Screening Program In Harris County, Texas, Hyun-Seok Kim, Rosalia Guerrero, Shane W Reader, Maria Daheri, Maya Balakrishnan, Catherine L Troisi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions.

Veterinarians’ Attitudes And Practices Regarding Opioid-Related Vet Shopping Practices In Tri-State Appalachian Counties: An Exploratory Study, Falguni C Patel, Jeffrey A Raines, Richard W Kim, Karen Gruszynski, Robert E Davis, Manoj Sharma, Gilbert Patterson, Jason W Johnson, Vinayak K Nahar

Faculty, Staff and Students Publications

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States.

RESULTS: …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T Melia, Armando Paez, Gail Reid, Lisa M Chirch, Vera P Luther, Brian G Blackburn, Federico Perez, Emily Abdoler, Daniel R Kaul, Susan Rehm, Nada Harik, Alice Barsoumian, Anna K Person, Heather Yun, J David Beckham, Susan Boruchoff, Paloma F Cariello, James B Cutrell, Christopher J Graber, Dong Heun Lee, Eileen Maziarz, Molly L Paras, Raymund R Razonable, Roseanne Ressner, Anne Chen, Brian Chow, Gerome Escota, Erica Herc, Andrew Johnson, Ryan C Maves, Obinna Nnedu, Heather Clauss, Prathit Kulkarni, Paul S Pottinger, Jose A Serpa, Tanaya Bhowmick, Marvin Bittner, Darcy Wooten, Beata Casanas, Rachel Shnekendorf, Emily A Blumberg

Faculty, Staff and Students Publications

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

A Broad-Spectrum Antiviral Molecule, Ql47, Selectively Inhibits Eukaryotic Translation, Mélissanne De Wispelaere, Margot Carocci, Dominique J Burri, William J Neidermyer, Calla M Olson, Imme Roggenbach, Yanke Liang, Jinhua Wang, Sean P J Whelan, Nathanael S Gray, Priscilla L Yang

Faculty, Staff and Students Publications

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the …

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.