Diseases Commons^™

Associations Of Serum And Dialysate Potassium Concentrations With Incident Atrial Fibrillation In A Cohort Study Of Older Us Persons Initiating Hemodialysis For Kidney Failure, Austin Hu, Sai Liu, Maria E Montez-Rath, Pascale Khairallah, Jingbo Niu, Mintu P Turakhia, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Atrial fibrillation (AF) disproportionally affects persons on maintenance hemodialysis (HD). Associations of serum and dialysate potassium concentrations [K+] with AF incidence are poorly understood.

METHODS: We conducted a cohort study using Medicare claims merged with clinical data from a dialysis provider to determine whether serum-[K+] and/or dialysate-[K+] independently associated with AF incidence. Persons insured by fee-for-service Medicare aged ≥67 years at dialysis initiation and free from diagnosed AF prior to day 120 of dialysis were eligible. Serum-[K+] and dialysate-[K+] were assessed in 30-day intervals and patients were followed-up with for AF incidence in subsequent 30-day intervals.

RESULTS: During 2006 …

A Retrospective Study Of The Relationship Between Hypertension And Vestibular Disorders In Middle-Aged Women With And Without Hiv, Helen S Cohen, Michael W Plankey, Deanna Ware

Faculty, Staff and Students Publications

BACKGROUND: Patients often conflate the problem of lightheadedness from hypertension (HTN) and vertigo from a vestibular impairment, describing both problems as dizziness. The goal of the study was to learn if there is a relationship between measures of vestibular function and blood pressure.

METHODS: This retrospective study consisted of women who participated in a longitudinal study of the human immunodeficiency virus (HIV) and a control cohort of age-matched women without HIV. We used data from the point in time when participants were tested for vestibular functions with bi-thermal caloric tests and cervical vestibular evoked myogenic potentials; the data also included …

The Performance Of Afp, Afp-3, Dcp As Biomarkers For Detection Of Hepatocellular Carcinoma (Hcc): A Phase 3 Biomarker Study In The United States, Nabihah Tayob, Fasiha Kanwal, Abeer Alsarraj, Ruben Hernaez, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations.

METHODS: We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded …

Challenges And Opportunities In Academic Physiatry: An Environmental Scan, David C Morgenroth, Tiffany Knowlton, Susan Apkon, Cheri A Blauwet, Anthony S Burns, Cecilia Córdova Vallejos, Walter Frontera, Sandra L Hearn, Prakash Jayabalan, Peter A Lim, Alex Moroz, Danielle Perret, Danielle Powell, Matt Puderbaugh, W Evan Rivers, Gwendolyn Sowa, Monica Verduzco-Gutierrez, Pablo A Celnik

Faculty, Staff and Students Publications

Environmental scans determine trends in an organization's or field's internal and external environment. The results can help shape goals, inform strategic decision making, and direct future actions. The Association of Academic Physiatrists convened a strategic planning group in 2020, composed of physiatrists representing a diversity of professional roles, career stages, race and ethnicity, gender, disability status, and geographic areas of practice. This strategic planning group performed an environmental scan to assess the forces, trends, challenges, and opportunities affecting both the Association of Academic Physiatrists and the entire field of academic physiatry (also known as physical medicine and rehabilitation, physical and …

A Delicate Balance Between Antibody Evasion And Ace2 Affinity For Omicron Ba275, Jiandong Huo, Aiste Dijokaite-Guraliuc, Chang Liu, Daming Zhou, Helen M Ginn, Raksha Das, Piyada Supasa, Muneeswaran Selvaraj, Rungtiwa Nutalai, Aekkachai Tuekprakhon, Helen M E Duyvesteyn, Alexander J Mentzer, Donal Skelly, Thomas G Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Neil G Paterson, Mark A Williams, David R Hall, Megan Plowright, Thomas A H Newman, Hailey Hornsby, Thushan I De Silva, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J Dunachie, Andrew J Pollard, Teresa Lambe, Philip Goulder, Optic Consortium, Isaric4c Consortium, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor …

Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the …

The Potential Of Brain Stimulation Techniques For Substance Use Disorder Treatment, Antonio F Corno, Taylor S Koerner, Jorge D Salazar

Faculty, Staff and Student Publications

No abstract provided.

Mutations In The Transcriptional Regulator Mecp2 Severely Impact Key Cellular And Molecular Signatures Of Human Astrocytes During Maturation, Jialin Sun, Sivan Osenberg, Austin Irwin, Li-Hua Ma, Nigel Lee, Yangfei Xiang, Feng Li, Ying-Wooi Wan, In-Hyun Park, Mirjana Maletic-Savatic, Nurit Ballas

Faculty, Staff and Students Publications

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether MECP2 mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing MECP2 mutations greatly impact the key role of astrocytes in regulating overall brain bioenergetics and that these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal maturation, astrocytes rely on neurons to induce their complex stellate morphology and transcriptional changes. While MECP2 mutations cause cell-intrinsic aberrations in the astrocyte transcriptional landscape, surprisingly, they do not affect the neuron-induced …

Rare Variants Of Dermatofibrosarcoma Protuberans: Clinical, Histologic, And Molecular Features And Diagnostic Pitfalls, Celestine M Trinidad, Sintawat Wangsiricharoen, Victor G Prieto, Phyu P Aung

Faculty, Staff and Student Publications

Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor. Most variants are associated with a high risk of local recurrence and a low risk of metastasis. The classic histomorphology of this tumor is made up of uniform, spindle-shaped cells, arranged in a storiform pattern. Tumor cells characteristically infiltrate the underlying subcutis in a honeycomb pattern. Less common variants of DFSP have been identified: myxoid, pigmented, myoid, granular cell, sclerosing, atrophic, and fibrosarcomatous. Only the fibrosarcomatous variant has been shown to differ significantly from classic DFSP in terms of clinical outcome; fibrosarcomatous DFSP has been shown to be associated with a …

Monitoring And Modulating Diet And Gut Microbes To Enhance Response And Reduce Toxicity To Cancer Treatment, Anne Knisely, Yongwoo David Seo, Jennifer A Wargo, Manoj Chelvanambi

Faculty, Staff and Student Publications

The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can …

Using Cognitive Interviews To Improve A Measure Of Organizational Readiness For Implementation, Maria Mcclam, Lauren Workman, Emanuelle M Dias, Timothy J Walker, Heather M Brandt, Derek W Craig, Robert Gibson, Andrea Lamont, Bryan J Weiner, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: Organizational readiness is a key factor for successful implementation of evidence-based interventions (EBIs), but a valid and reliable measure to assess readiness across contexts and settings is needed. The R = MC

METHODS: We conducted 20 cognitive interviews with FQHC staff (clinical and non-clinical) in South Carolina and Texas. Participants were provided a subset of items from the readiness survey to review. A semi-structured interview guide was developed to elicit feedback from participants using "think aloud" and probing techniques. Participants were recruited using a purposive sampling approach and interviews were conducted virtually using Zoom and WebEx. Participants were asked …

Is It Time To Re-Think Fast? A Systematic Review And Meta-Analysis Of Contrast-Enhanced Ultrasound (Ceus) And Conventional Ultrasound For Initial Assessment Of Abdominal Trauma, Bayu Sutarjono, Matthew Kessel, Dorian Alexander, Ekjot Grewal

Faculty, Staff and Student Publications

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examination using conventional ultrasound has limited utility for detecting solid organ injury. Therefore, this systematic review and meta-analysis compares the performance of contrast-enhanced ultrasound (CEUS) to conventional ultrasound when used as the initial assessment for abdominal trauma prior to computed tomography (CT) imaging.

METHODS: A systematic literature search of major databases was conducted of human studies investigating the diagnostic accuracy of conventional ultrasound and CEUS occurring prior to CT imaging for abdominal trauma. The study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The quality of studies …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

A Data-Driven Approach To Construct A Molecular Map Of Trypanosoma Cruzi To Identify Drugs And Vaccine Targets, Swarsat Kaushik Nath, Preeti Pankajakshan, Trapti Sharma, Priya Kumari, Sweety Shinde, Nikita Garg, Kartavya Mathur, Nevidita Arambam, Divyank Harjani, Manpriya Raj, Garwit Kwatra, Sayantan Venkatesh, Alakto Choudhoury, Saima Bano, Prashansa Tayal, Mahek Sharan, Ruchika Arora, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Recent Advances In Understanding Of Pathogenesis Of Alcohol-Associated Liver Disease, Xiaoqin Wu, Xiude Fan, Tatsunori Miyata, Adam Kim, Christina K Cajigas-Du Ross, Semanti Ray, Emily Huang, Moyinoluwa Taiwo, Rakesh Arya, Jianguo Wu, Laura E Nagy

Faculty, Staff and Student Publications

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz

Faculty, Staff and Students Publications

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ …

Epigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinomaepigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinoma, Amin H Nassar, Sarah Abou Alaiwi, Sylvan C Baca, Elio Adib, Rosario I Corona, Ji-Heui Seo, Marcos A S Fonseca, Sandor Spisak, Talal El Zarif, Viktoria Tisza, David A Braun, Heng Du, Monica He, Abdallah Flaifel, Michel Alchoueiry, Thomas Denize, Sayed G Matar, Andres Acosta, Sachet Shukla, Yue Hou, John Steinharter, Gabrielle Bouchard, Jacob E Berchuck, Edward O'Connor, Connor Bell, Pier Vitale Nuzzo, Gwo-Shu Mary Lee, Sabina Signoretti, Michelle S Hirsch, Mark Pomerantz, Elizabeth Henske, Alexander Gusev, Kate Lawrenson, Toni K Choueiri, David J Kwiatkowski, Matthew L Freedman

Faculty, Staff and Student Publications

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional …

Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple Negative Breast Cancer Using Deep Learning On Multiparametric Mri, Zijian Zhou, Beatriz E Adrada, Rosalind P Candelaria, Nabil A Elshafeey, Medine Boge, Rania M Mohamed, Sanaz Pashapoor, Jia Sun, Zhan Xu, Bikash Panthi, Jong Bum Son, Mary S Guirguis, Miral M Patel, Gary J Whitman, Tanya W Moseley, Marion E Scoggins, Jason B White, Jennifer K Litton, Vicente Valero, Kelly K Hunt, Debu Tripathy, Wei Yang, Peng Wei, Clinton Yam, Mark D Pagel, Gaiane M Rauch, Jingfei Ma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Neoadjuvant systemic therapy (NAST) followed by surgery are currently standard of care for TNBC with 50-60% of patients achieving pathologic complete response (pCR). We investigated ability of deep learning (DL) on dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging acquired early during NAST to predict TNBC patients' pCR status in the breast. During the development phase using the images of 130 TNBC patients, the DL model achieved areas under the receiver operating characteristic curves (AUCs) of 0.97 ± 0.04 and 0.82 ± 0.10 for the training and the …

Approach To The Patient: Pharmacological Therapies For Fracture Risk Reduction In Adults With Osteogenesis Imperfecta, Winnie Liu, Brendan Lee, Sandesh C S Nagamani, Lindsey Nicol, Frank Rauch, Eric T Rush, V Reid Sutton, Eric Orwoll

Faculty, Staff and Students Publications

Context

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. The effectiveness of medications used for fracture reduction in adults with OI is understudied and practice recommendations are not well established. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis. Oral and intravenous bisphosphonates have been shown to improve bone mineral density (BMD) in adults with OI and are commonly used; however, conclusive data confirming fracture protection are lacking. Similarly, teriparatide appears to increase BMD, an effect …

Nudging Health Care Providers' Adoption Of Clinical Decision Support: Protocol For The User-Centered Development Of A Behavioral Economics-Inspired Electronic Health Record Tool, Safiya Richardson, Katherine Dauber-Decker, Jeffrey Solomon, Sundas Khan, Douglas Barnaby, John Chelico, Michael Qiu, Yan Liu, Devin Mann, Renee Pekmezaris, Thomas Mcginn, Michael Diefenbach

Faculty, Staff and Students Publications

BACKGROUND: The improvements in care resulting from clinical decision support (CDS) have been significantly limited by consistently low health care provider adoption. Health care provider attitudes toward CDS, specifically psychological and behavioral barriers, are not typically addressed during any stage of CDS development, although they represent an important barrier to adoption. Emerging evidence has shown the surprising power of using insights from the field of behavioral economics to address psychological and behavioral barriers. Nudges are formal applications of behavioral economics, defined as positive reinforcement and indirect suggestions that have a nonforced effect on decision-making.

OBJECTIVE: Our goal is to employ …

Correction To: Stabilization Of Mcl-1 By E3 Ligase Traf4 Confers Radioresistance, Ming Li, Feng Gao, Xiaoying Li, Yu Gan, Shuangze Han, Xinfang Yu, Haidan Liu, Wei Li

Faculty, Staff and Students Publications

No abstract provided.

Thrombectomy Outcomes With General Vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From The Extend-Ia Trials And Select Study, Amrou Sarraj, Gregory W Albers, Peter J Mitchell, Ameer E Hassan, Michael G Abraham, Spiros Blackburn, Gagan Sharma, Nawaf Yassi, Timothy J Kleinig, Darshan G Shah, Teddy Y Wu, Muhammad Shazam Hussain, Wondwoseen G Tekle, Santiago Ortega Gutierrez, Amin Nima Aghaebrahim, Diogo C Haussen, Gabor Toth, Deep Pujara, Ronald F Budzik, William Hicks, Nirav Vora, Randall C Edgell, Sabreena Slavin, Colleen G Lechtenberg, Laith Maali, Abid Qureshi, Lee Rosterman, Mohammad Ammar Abdulrazzak, Tareq Almaghrabi, Faris Shaker, Osman Mir, Ashish Arora, Sheryl Martin-Schild, Clark W Sitton, Leonid Churilov, Rishi Gupta, Maarten G Lansberg, Raul G Nogueira, James C Grotta, Geoffrey Alan Donnan, Stephen M Davis, Bruce C V Campbell

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.

METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes.

RESULTS: Of 725 treated with EVT, 299 (41%) received GA …

Topical Antibiotic Treatment In Dermatology, Matthew Dallo, Kavina Patel, Adelaide A Hebert

Faculty, Staff and Student Publications

Many indications in dermatology can be effectively managed with topical antibiotics, including acne vulgaris, wound infections, secondarily infected dermatitis, and impetigo. Dermatologists must be familiar with the wide spectrum of topical antibiotics available, including indications, mechanisms of action, adverse events, and spectra of activity. Dermatologists must also keep antibiotic resistance in mind when utilizing these medications. Due to the widespread use of topical antibiotics and their importance in dermatology, a literature review was performed using a systematic search of PubMed and Google Scholar with the terms topical antibiotics, skin infections, dermatology, antimicrobials, and inflammatory dermatoses to identify English-language articles published …

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Ifigeneia Tzannou, Mengfen Wu, Carlos Ramos, Ghadir Sasa, Caridad Martinez, Premal Lulla, Robert A Krance, Lauren Scherer, Daniel Ruderfer, Swati Naik, Claire Bocchini, Iain P Fraser, Badrish Patel, Dany Ward, Tao Wang, Helen E Heslop, Ann M Leen, Bilal Omer

Faculty, Staff and Students Publications

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

A Gain-Of-Function Tpc2 Variant R210c Increases Affinity To Pi(3,5)P2 And Causes Lysosome Acidification And Hypopigmentation, Qiaochu Wang, Zengge Wang, Yizhen Wang, Zhan Qi, Dayong Bai, Chentong Wang, Yuanying Chen, Wenjian Xu, Xili Zhu, Jaepyo Jeon, Jian Xiong, Chanjuan Hao, Michael Xi Zhu, Aihua Wei, Wei Li

Faculty, Staff and Student Publications

Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from a patient with albinism. TPC2 is an endolysosome and melanosome localized non-selective cation channel involved in regulating pigment production. Through inside-out recording of plasma membrane targeted TPC2 and direct recording of enlarged endolysosomal vacuoles, we reveal that the R210C mutant displays constitutive channel activation and markedly increased affinity to PI(3,5)P2. Mice harboring the homologous mutation, R194C, also exhibit hypopigmentation in the fur and skin, as well …

Transmission Of Carbapenem-Resistant Klebsiella Pneumoniae In Us Hospitals, Courtney L Luterbach, Liang Chen, Lauren Komarow, Belinda Ostrowsky, Keith S Kaye, Blake Hanson, Cesar A Arias, Samit Desai, Jason C Gallagher, Elizabeth Novick, Stephen Pagkalinawan, Ebbing Lautenbach, Glenn Wortmann, Robert C Kalayjian, Brandon Eilertson, John J Farrell, Todd Mccarty, Carol Hill, Vance G Fowler, Barry N Kreiswirth, Robert A Bonomo, David Van Duin

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals.

METHODS: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster.

RESULTS: Most patients …