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The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Advancing Medical Applications Of Cancer Nanotechnology: Highlighting Two Decades Of The Nci's Nanotechnology Characterization Laboratory Service To The Research Community, Rachael M Crist, Yechezkel Barenholz, Ahuva Cern, Kate N Clark, Pieter R Cullis, Cheryl Dean, Neil Desai, Mauro Ferrari, Matthieu Germain, Carmen A Giacomantonio, Emma Grabarnik, Piotr Grodzinski, Atara Hod, Barry E Kennedy, Ruvanthi N Kularatne, Glen S Kwon, Emmanuel Loeb, Erin B Noftall, Len Pagliaro, Morteza Rasoulianboroujeni, Alexander Roth, Darren Rowles, Kulbir Singh, Nicole F Steinmetz, Zhanna Yehtina, Yao Zhang, Daniel Zilbersheid, Jeffrey D Clogston, Stephan T Stern, Marina A Dobrovolskaia

Center for Medical Ethics and Health Policy Staff Publications

The Nanotechnology Characterization Laboratory (NCL) is a US federally funded resource providing characterization and expertise to the cancer nanomedicine research community. Founded as a formal partnership among the US National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the US National Institute of Standards and Technology (NIST), the NCL has spent two decades developing a one-of-a-kind service with broad multidisciplinary expertise to meet the needs of a rapidly evolving drug development field. To mark the 20th anniversary of the lab's founding, the NCL hosted a symposium to highlight the achievements of the cancer nanomedicine field, showcase novel, …

Placentas From Sars-Cov-2 Infection During Pregnancy Exhibit Foci Of Oxidative Stress And Dna Damage, Guilherme M Nobrega, Eliza R Mccoll, Arthur Antolini-Tavares, Renato T Souza, José Guilherme Cecatti, Maria Laura Costa, Indira U Mysorekar

Faculty, Staff and Students Publications

Problem: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.

Method of study: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Multidisciplinary Approach To Treating Complex Immune Dysregulation Disorders: An Adaptive Model For Institutional Implementation, Lauren A Henderson, Roshini S Abraham, Aisha Ahmed, Lindsey Blount, Scott W Canna, Natalia S Chaimowitz, Shanmuganathan Chandrakasan, Bria Coates, James A Connelly, Megan A Cooper, Christine N Duncan, Anthony French, Melissa Hazen, Michelle L Hermiston, Brian Nolan, Anish Ray, Melissa J Rose, Lisa Forbes Satter, Grant Schulert, Sara Kristen Sexson Tejtel, Tiphanie Vogel, Kelly Walkovich, Matt S Zinter, Edward M Behrens

Faculty, Staff and Students Publications

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]). However, published information on the composition and function of immMDTs is sparse, and there is little guidance for those seeking to establish or optimize an immMDT. To inform this review, we assembled a panel of …

Eradication Rates Of Empiric Helicobacter Pylori Treatment Regimens By Race/Ethnicity In A Predominantly Immigrant Us Population, Min J Kim, Isiah Gonzalez, Nia M Choi, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background: Helicobacter pylori infections are mostly treated empirically (without antibiotic susceptibility testing). Determining eradication rates of different treatment regimens can inform antibiotic resistance. Our aim was to examine eradication rates of empiric H. pylori treatments based on treatment regimen, race/ethnicity and previous treatment status in a multiethnic U.S.

Materials and methods: This was a retrospective cross-sectional study of patients with a positive H. pylori test from 7/2021 to 4/2022 at Harris Health (Houston, Texas) who had received treatment and eradication testing within 1 year. We compared eradication rates based on treatment regimen, race/ethnicity, and prior treatment and examined other possible …

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …

The Infected Diabetic Foot: Incidence And Risk Factors For Dehiscence After Surgery For Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Jayer Chung, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to assess the incidence, risk factors and clinical outcomes of dehiscence after foot surgery in diabetic patients. We used pooled patient‐level data from two randomised clinical trials with 240 diabetic patients who required foot surgery for infections. Most patients (n = 180, 75.0%) had surgical wound closure. We defined dehisced surgical wounds (DSW) when the surgical site was not completely epithelialized with no drainage after sutures/staples were removed with a 2‐week validation of healing. We evaluated the time to heal, re‐infection, re‐ulceration, hospital admissions and amputations. Moderate and severe infection was based on criteria of the …

Leveraging Human Microbiomes For Disease Prediction And Treatment, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision …

Cervical Cancer In Women With Hiv: A Call To Action For Equitable Prevention In Low- And Middle-Income Countries, Jonathan Klutse, Yeena Abla Tay, Dzidzor Aku Attoh, Emmanuel Frimpong Gyekye, Charlotte Borteley Bortey, Esenam Dzifa Buatsi, Charlayne Cherylyn Oppong, Helena Lamptey, Collins Stephen Ahorlu, George Boateng Kyei, Evelyn Yayra Bonney

2020-Current year OA Pubs

Cervical cancer is preventable; however, it remains the leading cause of death in low- and middle-income countries (LMICs). Women with HIV (WWHs) have a sixfold higher risk of developing and dying from cervical cancer than women without HIV. Cervical cancer can be prevented by vaccination against high-risk human papillomaviruses (hrHPVs) and by screening for and treating precancer cervical lesions. While these preventive measures are routinely available to WWHs in developed countries, they are lacking in most LMICs, where the burden of HIV and cervical cancer is the highest. To prevent cervical cancer deaths among WWHs in LMICs, it is imperative …

Th9 Cells Provide Protective Tb Immunity, Mei Xia, Azra Blazevic, Huan Ning, Christopher S Eickhoff, Chad E Storer, Richard D Head, Jianguo Liu, Jessica Jarvela, David Stoeckel, Erin Rakey, Jan Tennant, Daniel L Miller, Kathleen R Holloway, Richard F Silver, Daniel F Hoft

2020-Current year OA Pubs

INTRODUCTION: CD4+ Th9 cells have been associated with inflammatory and allergic diseases. IL-9/Th9 can function as both positive and negative immune regulators, but their protective effects against

METHODS: To study TB-specific Th9 protective effects, we generated Th9 cells from ESAT6-specific TCR transgenic mice and healthy human donors.

RESULTS: Both murine and human Th9 cells significantly inhibited intracellular mycobacterial growth. In both

DISCUSSION: Th9 cells can provide important protection against Mtb infection, and should be targeted with future TB vaccine strategies. Furthermore, Th9 cells appear to utilize a novel protective mechanism independent from Th1-mediated protective responses.

Molecular Chaperones At The Host-Virus Interface: Heat Shock Protein Roles In Hiv-1 And Emerging Insights For Hiv-2 And Dual Infection, Sabastine Eugene Arthur, Kirk Klogo, Emmanuel Kobina Mensah, Maame Ama Pentsiwa Cudjoe, Adomia Baaba Mensah, Nyamekye Amoabeng Ankrah, Catherine Laaripuoh Omosule, Evelyn Yayra Bonney, George Boateng Kyei

2020-Current year OA Pubs

Heat shock proteins (HSPs) are essential molecular chaperones involved in protein folding, cellular stress responses, and homeostasis. Recent studies reveal their critical and dual roles in the human immunodeficiency virus (HIV) life cycle, both promoting and restricting viral replication, latency, and immune modulation. This review synthesizes current evidence on how key HSP families, HSP70, HSP90, and HSP40, interact with HIV proteins such as Tat, Rev, Nef, and Vpx, affecting viral transcription, protein trafficking, and latency. We also highlight Heat Shock Factor 1 (HSF1) as a direct regulator of the HIV-1 long terminal repeat (LTR), facilitating latency reversal via recruitment of …

Barriers And Facilitators To Implementing A Task-Sharing Mental Health Intervention For Sickle Cell Disease Populations In Low- And Middle-Income Countries: A Qualitative Analysis Using The Consolidated Framework For Implementation Research (Cfir), John Patena, Leah Elster, Tania Hameed, Sumedha Kulkarni, Alden Yuanhong Lai, Annika C Sweetland, Joyce Gyamfi, Temitope Ojo, Angela Odoms-Young, Charmaine Royal, Emmanuel Peprah

2020-Current year OA Pubs

BACKGROUND: People living with Sickle Cell Disease (SCD) experience higher rates of common mental disorders (CMD). There is an alarming treatment gap in the provision of adequate mental health services for CMDs in low- and middle-income countries (LMIC). One solution is the implementation of task-sharing interventions such as the Friendship Bench which utilizes concepts of problem-solving therapy (PST). This investigation uses a qualitative study design to evaluate the acceptability and feasibility of implementing a PST-based task-sharing mental health intervention for SCD populations in LMICs using the Consolidated Framework for Implementation Research (CFIR).

METHODS: Purposive, convenience, and snowball sampling strategies were …

A Case Report Of Long-Latency Evoked Diaphragm Potentials After Exposure To Acute Intermittent Hypoxia In Post-West Nile Virus Meningoencephalitis, Joseph F. Welch, Erica A. Dale, Jayakrishnan Nair, Paul W. Davenport, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

We present a case report of a 42-year-old female with post-West Nile virus meningoencephalitis who exhibited unique, long-latency diaphragm potentials evoked by transcranial and cervical magnetic stimulation after exposure to acute intermittent hypoxia (AIH). The subject was recruited for a study investigating AIH effects on respiratory motor function in healthy individuals. She had contracted West Nile virus infection 5 years before assessment that resulted in hospitalization and persistent allodynia but was not reported to the research team. During the study, transcranial (TMS) and cervical (CMS) magnetic stimulation were performed before and 30-60 min after a single presentation of AIH [15, …

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen

Approved Car-T Therapies Have Reproducible Efficacy And Safety In Clinical Practice, Daniel Goyco Vera, Hiral Waghela, Mohamed Nuh, Jonathan Pan, Premal Lulla

Faculty, Staff and Students Publications

CAR-T cell therapy has established itself as a highly effective treatment for hematological malignancies. There are currently six commercial CAR-T products that have been FDA approved for diseases such as B-ALL, LBCL, MCL, FL, MM, and CLL/SLL. "Real-world" studies allow us to evaluate outcomes from the general population to determine their efficacy and safety compared to those who were included in the original trials. Based on several well conducted "Real-world" studies that represent diverse populations, we report that outcomes from the original trials that led to the approval of these therapies are comparable to those in practice.

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal

Faculty, Staff and Students Publications

BACKGROUND: The Triglyceride-glucose (TyG) index represents a simple, cost-effective, and valid proxy for insulin resistance. This surrogate marker has also been proposed as a predictor of metabolic and cardiovascular disease (CVD). In this descriptive review, we aimed to assess the utility of the TyG index as a predictive biomarker of cardiometabolic diseases.

METHODS: A search was conducted in PubMed, and Web of Science to identify cross-sectional and more importantly prospective studies examining the use of the TyG index as a predictive biomarker. The following terms were utilized in addition to the TyG index: "insulin resistance", "metabolic syndrome", "diabetes"; "cardiovascular diseases". …

Effects On Maternal And Pregnancy Outcomes Of First-Trimester Malaria Infection Among Nulliparous Women From Kenya, Zambia, And The Democratic Republic Of The Congo, Sequoia I. Leuba, Daniel Westreich, Carl L. Bose, Andrew F. Olshan, Steve M. Taylor, Antoinette Tshefu, Adrien Lokangaka, Waldemar A. Carlo, Elwyn Chomba, Musaku Mwenechanya, Edward A. Liechty, Sherri L. Bucher, Osayame A. Ekhaguere, Fabian Esamai, Paul Nyongesa, Saleem Jessani, Sarah Saleem, Robert L. Goldenberg, Janet L. Moore, Tracy L. Nolen, Jennifer Hemingway-Foday, Elizabeth M. Mcclure, Marion Koso-Thomas, Richard Derman, Matthew Hoffman, Steven R. Meshnick, Melissa Bauserman

Department of Medicine Faculty Papers

BACKGROUND: Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes.

METHODS: In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation.

RESULTS: Compared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth …

Rna-Dependent Rna Polymerase Of Predominant Human Norovirus Forms Liquid-Liquid Phase Condensates As Viral Replication Factories, Soni Kaundal, Ramakrishnan Anish, B Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E Crawford, Jeroen Pollet, Fabio Stossi, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. …

The Plasmodium Falciparum Ncr1 Transporter Is An Antimalarial Target That Exports Cholesterol From The Parasite's Plasma Membrane, Zhemin Zhang, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,

Influenza Knowledge And Barriers To Vaccination In Immunosuppressed Patients In The Pediatric Rheumatology Clinic., Julia G. Harris, Leslie Favier, Jordan T. Jones, Maria Ibarra, Michael J. Holland, Emily Fox, Kelly Jensen, Ashley K. Sherman, Ashley M. Cooper

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Most patients with a pediatric rheumatic disease are at increased risk of influenza due to immunosuppressive medication use. Despite initial quality improvement efforts, our influenza vaccination rate plateaued at 72%, which prompted a survey of patients and families to assess provider vaccine recommendations, influenza knowledge, and barriers to influenza vaccination.

METHODS: Patients on immunosuppressive medication or their parent were eligible to complete a survey between July 2019 and January 2020. Survey questions assessed demographics, rheumatology diagnosis, immunosuppressive medication(s), influenza vaccination recommendation, patient/parent influenza knowledge, and barriers to influenza vaccination. Influenza vaccination rates for immunosuppressed patients were acquired each influenza …

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …

Cutaneous Nodules Secondary To Mycobacterium Avium Complex In A Patient With Human Immunodeficiency Virus, Jay Patel, Shannon Sayyadioskoie, Hanna Siatecka, Theodore Rosen

Faculty, Staff and Students Publications

We present a patient with human immunodeficiency virus who developed multiple painful lesions that previously in the past had speciated as Cryptococcus neoformans cutaneously, and in the lung. Despite induction therapy for presumed re-infection, the patient did not improve so a biopsy was performed and this was speciated as Mycobacterium avium complex, with final diagnosis being disseminated Mycobacterium avium complex. This case highlights the importance of considering a broad differential diagnosis for any new lesions regardless of prior culture data.

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …

Correlation Of Genogroup I, Genotype 1 (Gi.1) Norovirus Neutralizing Antibody Levels With Gi.1 Histo-Blood Group Antigen-Blocking Antibody Levels, Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Background: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.

Methods: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.

Results: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.

Conclusions: Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate …

Elevated Ambient Temperature Associated With Reduced Infectious Disease Test Positivity Rates: Retrospective Observational Analysis Of Statewide Covid-19 Testing And Weather Across California Counties., Nicholas Wing-Ping Kwok, Joshua Pevnick, Keith Feldman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: From medication usage to the time of day, a number of external factors are known to alter human body temperature (BT), even in the absence of underlying pathology. In select cases, clinical guidance already suggests the consideration of clinical and demographic factors when interpreting BT, such as a decreased threshold for fever as age increases. Recent work has indicated factors impacting BT extend to environmental conditions including ambient temperature. However, the effect sizes of these relationships are often small, and it remains unclear if such relationships result in a meaningful impact on real-world health care practices.

OBJECTIVE: Temperature remains …

Staphylococcus Epidermidis St2 Strains Associated With Bloodstream Infections Contain A Unique Mobile Genetic Element Encoding A Plasmin Inhibitor, Amy A Gomez, Clara Kjerfve, Minseo Choi, Wen Liu, Kelly Churion, Sheila Thomas, Holger Rohde, Sam Shelburne, Jon T Skare, Magnus Hook, Srishtee Arora

Faculty, Staff and Student Publications

Staphylococcus epidermidis, a common commensal bacterium, is a leading cause of nosocomial catheter-associated bloodstream infections. S. epidermidis sequence type 2 (ST2) is specifically recognized globally for causing invasive disease. In this study, we identified a novel putative integrated conjugative element, pICE-Sepi-ST2, unique to the genomes of S. epidermidis ST2. Our investigation identified pICE-Sepi-ST2 in all ST2 isolates from bloodstream infections. Meanwhile, ST2 isolates from other infection sources, such as catheters, prosthetic joints, and fracture fixations, showed variable pICE-Sepi-ST2 prevalence. pICE-Sepi-ST2 encodes two putative cell wall anchored proteins that we have designated SesX and SesY. Biochemical characterization of SesY revealed …

Nomenclature For Human And Animal Fungal Pathogens And Diseases: A Proposal For Standardized Terminology, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Maiken Cavling Arendrup, Andrew Borman, Sharon Chen, Anuradha Chowdhary, Robert C Colgrove, Oliver A Cornely, David W Denning, Philippe J Dufresne, Laura Filkins, Jean-Pierre Gangneux, Josepa Gené, Andreas H Groll, Jaques Guillot, Gerhard Haase, Catriona Halliday, David L Hawksworth, Roderick Hay, Martin Hoenigl, Vit Hubka, Tomasz Jagielski, Hazal Kandemir, Sarah E Kidd, Julianne V Kus, June Kwon-Chung, Shawn R Lockhart, Jacques F Meis, Leonel Mendoza, Wieland Meyer, M Hong Nguyen, Yinggai Song, Tania C Sorrell, J Benjamin Stielow, Rachel Vilela, Roxana G Vitale, Nancy L Wengenack, P Lewis White, Luis Ostrosky-Zeichner, Sean X Zhang

Faculty, Staff and Student Publications

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately …