Internal Medicine Commons^™

Community-Acquired Pneumonia: The Importance Of The Early Detection Of Drug-Resistant Organisms, Sai Doppalapudi, Muhammad Adrish

Faculty, Staff and Students Publications

Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States. While community-acquired pneumonia (CAP) is generally considered an acute time-limited illness, it is associated with high long-term mortality, with nearly one-third of patients requiring hospitalization dying within one year. An increasing trend of detecting multidrug-resistant (MDR) organisms causing CAP has been observed, especially in the Western world. In this editorial, we discuss about a publication by Jatteppanavar

Driving Pressure Decoded: Precision Strategies In Adult Respiratory Distress Syndrome Management, Muhammad Adrish, Sai Doppalapudi, Dmitry Lvovsky

Faculty, Staff and Students Publications

Mechanical ventilation (MV) is an important strategy for improving the survival of patients with respiratory failure. However, MV is associated with aggravation of lung injury, with ventilator-induced lung injury (VILI) becoming a major concern. Thus, ventilation protection strategies have been developed to minimize complications from MV, with the goal of relieving excessive breathing workload, improving gas exchange, and minimizing VILI. By opting for lower tidal volumes, clinicians seek to strike a balance between providing adequate ventilation to support gas exchange and preventing overdistension of the alveoli, which can contribute to lung injury. Additionally, other factors play a role in optimizing …

Social Determinants Of Health And Other Predictors In Initiation Of Treatment With Cdk4/6 Inhibitors For Hr+/Her2- Metastatic Breast Cancer, Ravi K Goyal, Sean D Candrilli, Susan Abughosh, Hua Chen, Holly M Holmes, Michael L Johnson

Faculty, Staff and Student Publications

In hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) have replaced endocrine therapy alone as the standard of care; however, several barriers to treatment initiation still exist. We assessed social determinants of health (SDOH) and other factors associated with the initiation of CDK4/6i for HR+/HER2- MBC in the Medicare population. Using a retrospective cohort design, patients aged ≥65 years and diagnosed during 2015-2017 were selected from the SEER-Medicare database. Time from MBC diagnosis to first CDK4/6i initiation was the study outcome. The effect of SDOH measures and other predictors on the …

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …

Specific Gravity Improves Identification Of Clinically Significant Quantitative Proteinuria From The Dipstick Urinalysis, Meredith C Mcadams, L Parker Gregg, Pin Xu, Song Zhang, Michael Li, Ella Carroll, Vaishnavi Kannan, Duwayne L Willett, S Susan Hedayati

Faculty, Staff and Students Publications

KEY POINTS: Urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio are frequently obtained and represent possible tools for screening for proteinuria and thus early CKD. Adding specific gravity to dipstick proteinuria improves the ability to screen patients with clinically significant proteinuria and can be used to identify patients with early CKD.

BACKGROUND: CKD is often underdiagnosed during early stages when GFR is preserved because of underutilization of testing for quantitative urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR). Semiquantitative dipstick proteinuria (DSP) on urinalysis is widely obtained but not accurate for identifying clinically significant proteinuria.

METHODS: We identified all patients …

The Association Of Self-Reported Sleep And Circadian Measures With Glycemic Control And Diabetes Complications Among Young Adults With Type 2 Diabetes, Dorit Koren, Kristen L Knutson, Brian K Burke, Kimberly L Drews, Fida Bacha, Lorraine Katz, Marsha D Marcus, Siripoom Mckay, Kristen Nadeau, Babak Mokhlesi, Today Study Group

Children’s Nutrition Research Center Staff Publications

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were …

Fibroblast Subpopulations In Systemic Sclerosis: Functional Implications Of Individual Subpopulations And Correlations With Clinical Features, Honglin Zhu, Hui Luo, Brian Skaug, Tracy Tabib, Yi-Nan Li, Yongguang Tao, Alexandru-Emil Matei, Marka A Lyons, Georg Schett, Robert Lafyatis, Shervin Assassi, Jörg H W Distler

Faculty, Staff and Student Publications

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal …

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …

Pegvaliase For The Treatment Of Phenylketonuria: Final Results Of A Long-Term Phase 3 Clinical Trial Program, Cary O Harding, Nicola Longo, Hope Northrup, Stephanie Sacharow, Rani Singh, Janet A Thomas, Jerry Vockley, Roberto T Zori, Kaleigh Bulloch Whitehall, Joshua Lilienstein, Kristin Lindstrom, Drew G Levy, Shaun Jones, Barbara K Burton

Faculty, Staff and Student Publications

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled blood Phe concentrations (>600 μmol/L) despite prior management. Aggregated results from the PRISM clinical trials demonstrated substantial and sustained reductions in blood Phe with a manageable safety profile, but also noted individual variation in time to and dose needed for a first response. This analysis reports longer-term aggregate findings …

Adverse Pregnancy Outcomes And Long-Term Mortality In Women, Casey Crump, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Importance: Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions.

Objective: To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.

Design, setting, and participants: This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had …

A Prospective Observational Study Of Disease Severity And Mortality In Hispanic American Patients With Systemic Sclerosis, Bochra Jandali, Marka Lyons, Julio Charles, Meng Zhang, Samuel Theodore, Claudia Pedroza, Maureen D Mayes, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To characterize disease manifestations in Hispanic American patients with systemic sclerosis (SSc) in comparison with non-Hispanic White and Black patients.

Methods: Longitudinal clinical characteristics were collected prospectively in the Genetics versus Environment in Scleroderma Outcome Study cohort. All patients fulfilled the classification criteria for SSc and had a disease duration less than five years at enrollment.

Results: A cohort of 427 patients, consisting of 124 Hispanic, 220 non-Hispanic White, and 83 non-Hispanic Black participants were examined. At enrollment, Hispanic patients were significantly younger but had longer disease duration, higher frequency of U1-RNP positivity as well as concurrent systemic lupus …

Covid-19 Ethics: Unique Aspects And A Review As Of Early 2024, Wayne X Shandera

Faculty, Staff and Students Publications

COVID-19 presents a variety of ethical challenges in a set of arenas, arenas not always considered in past pandemics. These challenges include issues related to autonomy, distributive ethics, and the establishment of policies of equity and justice. Methods are a literature review based on regular editing of an online textbook during the COVID-19 outbreak and a literature review using key ethical terms. Patients are confronted with new issues related to autonomy. Providers need to expand their concepts of ethical issues to include decisions based on proportionality and public health ethics. The public health sector needs to assess the beneficence of …

Cystatin C Use For Ckd Detection In The Veterans Health Administration System: A Qualitative Study Of Barriers And Facilitators, Julio A Lamprea-Montealegre, Abigail Shapiro, Natalie A B Bontrager, Dena E Rifkin, Simerjot K Jassal, Lucile Parker Gregg, Sankar D Navaneethan, Krista Navarra, Michael G Shlipak, Michelle M Estrella, Virginia Wang

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: The measurement of cystatin C has been recommended to enhance chronic kidney disease (CKD) detection and risk stratification in clinical practice. This study gathered insights into the perceptions and experiences of clinical staff regarding the use of cystatin C in CKD detection within the Veterans Health Administration (VHA) system.

STUDY DESIGN: A qualitative approach was employed to explore barriers and facilitators of clinical staff regarding the use of cystatin C in CKD detection within the VHA system. The Organizational Theory of Implementation Effectiveness informed the development of a semistructured interview guide.

SETTING & PARTICIPANTS: Health care providers, …

Persistent ∆Fosb Expression Limits Recurrent Seizure Activity And Provides Neuroprotection In The Dentate Gyrus Of App Mice, Gabriel S Stephens, Jin Park, Andrew Eagle, Jason You, Manuel Silva-Pérez, Chia-Hsuan Fu, Sumin Choi, Corey P St Romain, Chiho Sugimoto, Shelly A Buffington, Yi Zheng, Mauro Costa-Mattioli, Yin Liu, A J Robison, Jeannie Chin

Faculty, Staff and Student Publications

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection …

Autologous Her2-Specific Car T Cells After Lymphodepletion For Advanced Sarcoma: A Phase 1 Trial, Meenakshi Hegde, Shoba Navai, Christopher Derenzo, Sujith K Joseph, Khaled Sanber, Mengfen Wu, Ahmed Z Gad, Katherine A Janeway, Matthew Campbell, Dolores Mullikin, Zeid Nawas, Catherine Robertson, Pretty R Mathew, Huimin Zhang, Birju Mehta, Raksha R Bhat, Angela Major, Ankita Shree, Claudia Gerken, Mamta Kalra, Rikhia Chakraborty, Sachin G Thakkar, Olga Dakhova, Vita S Salsman, Bambi Grilley, Natalia Lapteva, Adrian Gee, Gianpietro Dotti, Riyue Bao, Ahmed Hamed Salem, Tao Wang, Malcolm K Brenner, Helen E Heslop, Winfried S Wels, M John Hicks, Stephen Gottschalk, Nabil Ahmed

Faculty, Staff and Students Publications

In this prospective, interventional phase I study (NCT00902044) for patients with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T-cells (HER2-CART) after lymphodepletion with cyclophosphamide (Cy) +/− fludarabine (Flu): 1×108 T-cells/m2 after Flu (cohort A) or Flu/Cy (cohort B), and 1×108 CAR-positive T-cells/m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2-CART after lymphodepletion. The determination of antitumor responses was the secondary outcome. Thirteen patients were treated in 14 enrollments with 7 receiving multiple infusions. HER2-CART expanded after 19 of 21 infusions. Nine of 12 patients in cohorts A and …

Challenges And Implications For Substance Use And Mental Healthcare Among Under-Resourced Women In The Covid-19 Era, Maria C Mejia, Alicia Kowalchuk, Sandra J Gonzalez, Muktha Nair, Lisa Webb, Nadine Scamp

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic exacerbated disparities in mental healthcare and substance use disorder (SUD) treatment access, especially in under-resourced communities. This study aimed to comprehend the experiences of under-resourced women with SUD during the pandemic, their knowledge and attitudes toward it, and its impact on substance use and treatment access.

METHODS: A cross-sectional study included 66 under-resourced women receiving medically managed withdrawal treatment at a community residential SUD center. Data collection occurred between November 2021 and August 2022, utilizing a 75-item instrument covering COVID-19 exposure and its impact on health, substance use, treatment access, vaccination status, beliefs, and knowledge. Descriptive …

Identification Of Sleep Phenotypes In Copd Using Machine Learning-Based Cluster Analysis, Javad Razjouyan, Nicola A Hanania, Sara Nowakowski, Ritwick Agrawal, Amir Sharafkhaneh

Faculty, Staff and Students Publications

BACKGROUND: Disturbed sleep in patients with COPD impact quality of life and predict adverse outcomes.

RESEARCH QUESTION: To identify distinct phenotypic clusters of patients with COPD using objective sleep parameters and evaluate the associations between clusters and all-cause mortality to inform risk stratification.

STUDY DESIGN AND METHODS: A longitudinal observational cohort study using nationwide Veterans Health Administration data of patients with COPD investigated for sleep disorders. Sleep parameters were extracted from polysomnography physician interpretation using a validated natural language processing algorithm. We performed cluster analysis using an unsupervised machine learning algorithm (K-means) and examined the association between clusters and mortality …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Faculty, Staff and Student Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

Pulmonary Hypertension And Hyperglycemia-Not A Sweet Combination, Or Bruck, L M Pandit

Faculty, Staff and Students Publications

Hyperglycemia and pulmonary hypertension (PH) share common pathological pathways that lead to vascular dysfunction and resultant cardiovascular complications. These shared pathologic pathways involve endothelial dysfunction, inflammation, oxidative stress, and hormonal imbalances. Individuals with hyperglycemia or pulmonary hypertension also possess shared clinical factors that contribute to increased morbidity from both diseases. This review aims to explore the relationship between PH and hyperglycemia, highlighting the mechanisms underlying their association and discussing the clinical implications. Understanding these common pathologic and clinical factors will enable early detection for those at-risk for complications from both diseases, paving the way for improved research and targeted therapeutics.

Factors Associated With Intention To Implement Sbi And Sud Treatment: A Survey Of Primary Care Clinicians In Texas Enrolled In An Online Course, Alicia Kowalchuk, Tiffany G Ostovar-Kermani, Kylie Schaper, Larissa Grigoryan, Jacqueline M Hirth, Maria Carmenza Mejia, Kiara K Spooner, Roger J Zoorob

Faculty, Staff and Students Publications

BACKGROUND: Substance use disorder (SUD) presents a range of public health challenges and consequences. Despite the prevention potential of screening and brief intervention (SBI) in the primary care setting, implementation is low. The purpose of this study was to assess associations of primary care clinicians' knowledge of SBI and SUD treatment, subjective norms, and perceived behavioral control with intention to incorporate SBI and SUD treatment into regular clinical practice.

METHODS: This online survey was administered to primary care clinicians who practice in Texas between March 1, 2021, and February 5, 2023. Survey questions were mapped to factors in the Theory …

Reaction Mechanisms Of H2s Oxidation By Naphthoquinones, Kenneth R Olson, Kasey J Clear, Tsuyoshi Takata, Yan Gao, Zhilin Ma, Ella Pfaff, Anthony Travlos, Jennifer Luu, Katherine Wilson, Zachary Joseph, Ian Kyle, Stephen M Kasko, Prentiss Jones, Jon Fukuto, Ming Xian, Gang Wu, Karl D Straub

Faculty, Staff and Student Publications

1,4-naphthoquinones (NQs) catalytically oxidize H2S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H2S oxidation by NQs with various substituent groups. In general, the order of H2S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H2S to polysulfides and sulfoxides. …

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Intrabiliary Metastasis Of Colorectal Mucinous Adenocarcinoma Mimicking Choledocholithiasis 18 Years After The Primary Tumor, Sumaya Abdul Ghaffar, David Pfau, Nikhil Madhuripan, Robert Christopher Harmon, Antonio Galvao Neto, Ana Luiza Gleisner

Faculty, Staff and Student Publications

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma …

Coronary Pathophysiology Underlying The Obesity Paradox, Linh Bui, Monica Patel, K Lance Gould

Faculty, Staff and Student Publications

No abstract provided.

Tenapanor As Therapy For Hyperphosphatemia In Maintenance Dialysis Patients: Results From The Optimize Study, Stuart M Sprague, Daniel E Weiner, David P Tietjen, Pablo E Pergola, Steven Fishbane, Geoffrey A Block, Arnold L Silva, Stephen Z Fadem, Robert I Lynn, George Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M Spiegel, David P Rosenbaum

Faculty, Staff and Students Publications

KEY POINTS: Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.

METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline

RESULTS: By part A end point, 34.4% (

CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P …