Medicine and Health Sciences Commons^™

Trem2 On Microglia Cell Surface Binds To And Forms Functional Binary Complexes With Heparan Sulfate Modified With 6-O-Sulfation And Iduronic Acid, Ilayda Ozsan Mcmillan, Li Liang, Guowei Su, Xuehong Song, Kelly Drago, Hua Yang, Claudia Alvarez, Amika Sood, James Gibson, Robert J Woods, Chunyu Wang, Jian Liu, Fuming Zhang, Tom J Brett, Lianchun Wang

2020-Current year OA Pubs

The triggering receptor expressed on myeloid cells-2 (TREM2), a pivotal innate immune receptor, orchestrates functions such as inflammatory responses, phagocytosis, cell survival, and neuroprotection. TREM2 variants R47H and R62H have been associated with Alzheimer's disease, yet the underlying mechanisms remain elusive. Our previous research established that TREM2 binds to heparan sulfate (HS) and variants R47H and R62H exhibit reduced affinity for HS. Building upon this groundwork, our current study delves into the interplay between TREM2 and HS and its impact on microglial function. We confirm TREM2's binding to cell surface HS and demonstrate that TREM2 interacts with HS, forming HS-TREM2 …

Low-Dose Ondansetron: A Candidate Prospective Precision Medicine To Treat Alcohol Use Disorder Endophenotypes, Bankole Johnson, Hannu Alho, Giovanni Addolorato, Otto Michael Lesch, Jonathan Chick, Lei Liu, Vinzant Schuyler

2020-Current year OA Pubs

BACKGROUND: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise …

Utility Of Eosinophil Peroxidase As A Biomarker Of Eosinophilic Inflammation In Asthma, Monica Tang, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.

OBJECTIVE: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.

METHODS: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3.

RESULTS: Over 3 years, EPX levels in patients with asthma were higher than normal …

Rhesus Rotavirus Nsp1 Mediates Extra-Intestinal Infection And Is A Contributing Factor For Biliary Obstruction, Enkai Li, Ningguo Feng, Qiru Zeng, Liliana Sanchez-Tacuba, Takahiro Kawagishi, Grace Branham, Gaopeng Hou, Zemin Wang, Harry B. Greenberg, Siyuan Ding

2020-Current year OA Pubs

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode …

Predictors Of Outcome And Symptomatic Intracranial Hemorrhage In Acute Basilar Artery Occlusions: Analysis Of The Pc-Search Thrombectomy Registry., Adam T Mierzwa, Ashley Nelson, Sami Al Kasab, Santiago Ortega Gutierrez, Juan Vivanco-Suarez, Mudassir Farooqui, Ashutosh P Jadhav, Shashvat Desai, Gabor Toth, Anas Alrohimi, Thanh N Nguyen, Piers Klein, Mohamad Abdalkader, Hisham Salahuddin, Aditya Pandey, Zachary Wilseck, Sravanthi Koduri, Niraj Vora, Nameer Aladamat, Khaled Gharaibeh, Ehad Afreen, Hisham Al-Hajala, Julie Shawver, Syed Zaidi, Mouhammad Jumaa

Neuroscience Articles

INTRODUCTION: Recent randomized controlled trials demonstrated superiority of mechanical thrombectomy compared to medical therapy in acute basilar artery occlusions, however, little data is available to guide clinicians in functional prognosis and risk stratification.

PATIENTS AND METHODS: Data from the retrospectively established PC-SEARCH Thrombectomy registry, which included patients with basilar artery occlusion from eight sites from January 2015 to December 2021, was interrogated. Outcomes were dichotomized into 90-day favorable (mRS ⩽ 3) and unfavorable (mRS > 3). Multivariate logistic regression analysis was performed with respect to the outcome groups and were adjusted for potential confounding baseline characteristics.

RESULTS: Four-hundred-forty-four patients were included …

Pembrolizumab Plus Carboplatin And Paclitaxel As First-Line Therapy For Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma (Keynote-B10): A Single-Arm Phase Iv Trial, Marcin Dzienis, Peter Oppelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).

METHODS: Eligible adults had previously untreated, histologically or cytologically confirmed R/M HNSCC regardless of PD-L1 status, measurable disease per RECIST v1.1 by blinded independent central review …

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W Clemens, Terence M Myckatyn, Arianna Di Napoli, Andrew L Feldman, Elaine S Jaffe, Cara L Haymaker, Steven M Horwitz, Kelly K Hunt, Marshall E Kadin, Colleen M Mccarthy, Roberto N Miranda, H Miles Prince, Fabio Santanelli Di Pompeo, Sari D Holmes, Linda G Phillips

Faculty, Staff and Student Publications

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

A Podcast On Practical Considerations In Patients With Advanced Urothelial Cancer Receiving First-Line Cisplatin- Or Carboplatin-Based Chemotherapy Followed By Avelumab Maintenance In A Changing Therapeutic Landscape, Jun Gong, Melissa A Reimers

2020-Current year OA Pubs

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy …

An Ordinal Clinical Score Predicts Seizure Freedom After Minimally Invasive Epilepsy Surgery, Adam S Dickey, Katie L Bullinger, Dayton Grogan, Melissa M Asmar, Abdulrahman Alwaki, Ammar Kheder, Veeresh Kumar N Shivamurthy, Razan R Faraj, Alexander Greven, Jon T Willie, Daniel L Drane, Robert E Gross

2020-Current year OA Pubs

OBJECTIVE: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients.

METHODS: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using …

An Expert Discussion On The Atypical Hemolytic Uremic Syndrome Nomenclature-Identifying A Road Map To Precision: A Report Of A National Kidney Foundation Working Group, Carla M Nester, Anuja Java, Et Al.

2020-Current year OA Pubs

The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to …

Tauroursodeoxycholic Acid Ameliorates Renal Injury Induced By Col4a3 Mutation, Shuwen Yu, Teija Suhas, Meei-Hua Lin, Jeffrey H Miner, Et Al.

2020-Current year OA Pubs

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed …

A Damaging Col6a3 Variant Alters The Mir31hg-Regulated Response Of Chondrocytes In Neocartilage Organoids To Hyperphysiologic Mechanical Loading, Niek Gc Bloks, Zainab Harissa, Giorgia Mazzini, Shaunak S Adkar, Amanda R Dicks, Ghazaleh Hajmousa, Nancy Steward, Roman I Koning, Aat Mulder, Berend B R De Koning, Margreet Kloppenburg, Rodrigo Coutinho De Almeida, Yolande Fm Ramos, Farshid Guilak, Ingrid Meulenbelt

2020-Current year OA Pubs

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR-Cas9 genome engineering in two established human induced pluripotent stem cell-derived in-vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi-omics (mRNA and lncRNA) approach in interaction with hyper-physiological mechanical loading …

Feasibility And Acceptability Of A Nurse-Led Telehealth Intervention (Bolster) To Support Patients With Peritoneal Carcinomatosis And Their Caregivers: A Pilot Randomized Clinical Trial, Rachel A Pozzar, Andrea C Enzinger, Catherine Howard, Anna Tavormina, Ursula A Matulonis, Susana Campos, Joyce F Liu, Neil Horowitz, Panagiotis A Konstantinopoulos, Carolyn Krasner, Jaclyn A Wall, Kate Sciacca, Larissa A Meyer, Charlotta Lindvall, Alexi A Wright

Faculty, Staff and Student Publications

Objective: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP).

Methods: Pilot feasibility RCT. Recently hospitalized adults with advanced …

Multi-Scale Variational Autoencoder For Imputation Of Missing Values In Untargeted Metabolomics Using Whole-Genome Sequencing Data, Chen Zhao, Kuan-Jui Su, Chong Wu, Xuewei Cao, Qiuying Sha, Wu Li, Zhe Luo, Tian Qing, Chuan Qiu, Lan Juan Zhao, Anqi Liu, Lindong Jiang, Xiao Zhang, Hui Shen, Weihua Zhou, Hong-Wen Deng

Faculty, Staff and Student Publications

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies.

Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-scale variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics …

Management Of Patients With Early-Stage Oropharyngeal Cancer With Clinically Positive Retropharyngeal Lymph Nodes, Luisa Encarnacion Jacomina, Amy Catherine Moreno

Faculty, Staff and Student Publications

No abstract provided.

Response-Adapted Ultralow-Dose Radiation Therapy For Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial, Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther, Penny Q Fang, Susan Y Wu, Loretta J Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael Steiner, Jason Westin, Sattva Neelapu, Maria A Rodriguez, Hun Ju Lee, Michael Wang, Christopher Flowers, Lei Feng, Bita Esmaeli

Faculty, Staff and Student Publications

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.

Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.

Design, setting, and participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between …

Ixazomib Plus Daratumumab And Dexamethasone: Final Analysis Of A Phase 2 Study Among Patients With Relapsed/Refractory Multiple Myeloma, Sosana Delimpasi, Meletios A Dimopoulos, Jan Straub, Argiris Symeonidis, Luděk Pour, Roman Hájek, Cyrille Touzeau, Viralkumar K Bhanderi, Jesus G Berdeja, Petr Pavlíček, Jeffrey V Matous, Pawel J Robak, Kaveri Suryanarayan, Alison Miller, Miguel Villarreal, Dasha Cherepanov, Jaydeep K Srimani, Huilan Yao, Richard Labotka, Robert Z Orlowski

Faculty, Staff and Student Publications

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity. Median age was 69 years; 14.8% of patients had International Staging System stage III disease; 14.8% had received three prior therapies. Patients received a median of 16 cycles of IDd. In 59 response-evaluable …

Inferring Super-Resolution Tissue Architecture By Integrating Spatial Transcriptomics With Histology, Daiwei Zhang, Amelia Schroeder, Hanying Yan, Haochen Yang, Jian Hu, Michelle Y Y Lee, Kyung S Cho, Katalin Susztak, George X Xu, Michael D Feldman, Edward B Lee, Emma E Furth, Linghua Wang, Mingyao Li

Faculty, Staff and Student Publications

Spatial transcriptomics (ST) has demonstrated enormous potential for generating intricate molecular maps of cells within tissues. Here we present iStar, a method based on hierarchical image feature extraction that integrates ST data and high-resolution histology images to predict spatial gene expression with super-resolution. Our method enhances gene expression resolution to near-single-cell levels in ST and enables gene expression prediction in tissue sections where only histology images are available.

Mutant Nrf2e79q Enhances The Promotion And Progression Of A Subset Of Oncogenic Ras Keratinocytes And Skin Tumors, John G Witherspoon, Jonathan R Hall, Dereje Jima, Hannah M Atkins, Nathan T Wamsley, Michael B Major, Bernard E Weissman, Robert C Smart

2020-Current year OA Pubs

Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2

Transvenous Tissue Sampling In The Diagnosis Of Intravascular Neoplasm., Christopher J Neely, Christopher M Huff, Andrew C Gordon, Raghu Kolluri, Kush R Desai

Heart and Vascular Articles

No abstract provided.

Comparing The Diagnostic Yield Of Germline Exome Versus Panel Sequencing In The Diverse Population Of The Texas Kidscanseq Pediatric Cancer Study, Lauren R Desrosiers-Battu, Tao Wang, Jacquelyn Reuther, George Miles, Hongzheng Dai, Eunji Jo, Heidi Russell, Robin Raesz-Martinez, Alva Recinos, Stephanie Gutierrez, Amy Thomas, Emily Berenson, Jessica Corredor, Kimberly Nugent, Rachel Wyatt Castillo, Rebecca Althaus, Rebecca Littlejohn, Shawn Gessay, Gail Tomlinson, Jonathan Gill, Juan Carlos Bernini, Kelly Vallance, Timothy Griffin, Sarah Scollon, Frank Y Lin, Christine Eng, Shashikant Kulkarni, Susan G Hilsenbeck, Angshumoy Roy, Amy L Mcguire, D Williams Parsons, Sharon E Plon

Faculty, Staff and Student Publications

Purpose: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population.

Patients and methods: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood.

Results: Cancer P/LP variants were reported by at least one platform in 103 of …

Comparison Of Outcomes Of Abdominoperineal Resection Vs Low Anterior Resection In Very-Low Rectal Cancer, Roberta L Muldoon, Alva J Bethurum, Adriana C Gamboa, Kevin Zhang, Fei Ye, Scott E Regenbogen, Sherif Abdel-Misih, Aslam Ejaz, Paul E Wise, Matthew Silviera, Jennifer Holder-Murray, Glen C Balch, Alexander T Hawkins

2020-Current year OA Pubs

BACKGROUND: The management of very-low rectal cancer is one of the most challenging issues faced by general and colorectal surgeons. Many feel compelled to pursue abdominoperineal resection (APR) over low anterior resection (LAR) to optimize oncologic outcomes. This study aimed to determine differences in long-term oncologic outcomes between patients undergoing APR or LAR for very-low rectal cancer.

METHODS: The United States Rectal Cancer Consortium (2010-2016) was queried for adults who underwent either APR or LAR for stage I-III rectal cancers < 5 cm from anorectal junction and met inclusion criteria. The primary outcome was disease-free survival. Secondary outcomes included overall survival, length of stay, complications, recurrence location, and perioperative factors.

RESULTS: A total of 431 patients with very-low rectal cancer who underwent APR or LAR were identified; 154 (35.7%) underwent …

An Interpretable Machine Learning-Based Cerebrospinal Fluid Proteomics Clock For Predicting Age Reveals Novel Insights Into Brain Aging, Justin Melendez, Yun Ju Sung, Miranda Orr, Andrew Yoo, Suzanne Schindler, Carlos Cruchaga, Randall Bateman

2020-Current year OA Pubs

Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to …

Genetic Risk Accentuates Dietary Effects On Hepatic Steatosis, Inflammation And Fibrosis In A Population-Based Cohort, Vincent L Chen, Xiaomeng Du, Antonino Oliveri, Yanhua Chen, Annapurna Kuppa, Brian D Halligan, Michael A Province, Elizabeth K Speliotes

2020-Current year OA Pubs

BACKGROUND & AIMS: Steatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has a differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank.

METHODS: We included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. The primary outcome was LFC, and secondary outcomes were iron-controlled T1 time (cT1, a …

Perioperative Risk Factors For Persistent Postsurgical Pain After Inguinal Hernia Repair: Systematic Review And Meta-Analysis, Harutyun Alaverdyan, Jooyoung Maeng, Peter K. Park, Kavya Narayana Reddy, Michael P Gaume, Lauren Yaeger, Michael M. Awad, Simon Haroutounian

2020-Current year OA Pubs

Persistent postsurgical pain (PPSP) is one of the most bothersome and disabling long-term complications after inguinal hernia repair surgery. Understanding perioperative risk factors that contribute to PPSP can help identify high-risk patients and develop risk-mitigation approaches. The objective of this study was to systematically review and meta-analyze risk factors that contribute to PPSP after inguinal hernia repair. The literature search resulted in 303 papers included in this review, 140 of which were used for meta-analyses. Our results suggest that younger age, female sex, preoperative pain, recurrent hernia, postoperative complications, and postoperative pain are associated with a higher risk of PPSP. …

Etomoxir-Carnitine, A Novel Pharmaco-Metabolite Of Etomoxir, Inhibits Phospholipases A2 And Mitochondrial Respiration, Sung Ho Moon, Xinping Liu, Christopher M Jenkins, Beverly Gibson Dilthey, Gary J Patti, Richard W Gross

2020-Current year OA Pubs

Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1), which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid β-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize ETO to etomoxir-carnitine (ETO-carnitine) prior to nearly complete ETO-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the …

Structure Of A Truncated Human Glcnac-1-Phosphotransferase Variant Reveals The Basis For Its Hyperactivity, Hua Li, Balraj Doray, Benjamin C Jennings, Wang-Sik Lee, Lin Liu, Stuart Kornfeld, Huilin Li

2020-Current year OA Pubs

Mutations that cause loss of function of GlcNAc-1-phosphotransferase (PTase) lead to the lysosomal storage disorder mucolipidosis II. PTase is the key enzyme of the mannose 6-phosphate (M6P) targeting system that is responsible for tagging lysosomal hydrolases with the M6P moiety for their delivery to the lysosome. We had previously generated a truncated hyperactive form of PTase termed S1S3 which was shown to notably increase the phosphorylation level of secreted lysosomal enzymes and enhance their uptake by cells. Here, we report the 3.4 Å cryo-EM structure of soluble S1S3 lacking both transmembrane domains and cytosolic tails. The structure reveals a high …

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W. Clemens, Terence M. Myckatyn, Arianna Di Napoli, Andrew L. Feldman, Elaine S. Jaffe, Cara L. Haymaker, Steven M. Horwitz, Kelly K. Hunt, Marshall E. Kadin, Colleen M Mccarthy, Roberto N. Miranda, H. Miles Prince, Fabio Santanelli Di Pompeo, Sari D. Holmes, Linda G. Phillips

2020-Current year OA Pubs

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

Outcomes Of Double-Valve Surgery For Infective Endocarditis Are Improving In The Modern Era, Paighton C Miller, Linda J Schulte, Theodore Marghitu, Shengxiang Huang, Tsuyoshi Kaneko, Ralph J Damiano, Puja Kachroo

2020-Current year OA Pubs

BACKGROUND: The incidence of infective endocarditis (IE) is rapidly increasing. Contemporary outcomes following high-risk double valve surgery (DVS) for IE are not well described.

METHODS: Between 2001 and 2021, 211 patients with IE underwent combined aortic and mitral valve surgery at a tertiary care referral center. Data from the Society of Thoracic Surgeons registry, including demographics, operative details, and outcomes, were collected. Risk factors for 30-day and 1-year-mortality were analyzed. Survival was analyzed using Kaplan-Meier and Cox proportional hazards modeling.

RESULTS: The study cohort had a male preponderance (73%), with a median age of 56 years (interquartile range [IQR], 44 …