Medicine and Health Sciences Commons^™

Strategies To Prevent Central Line-Associated Bloodstream Infections In Acute-Care Hospitals: 2022 Update, Niccolò Buetti, Jonas Marschall, Marci Drees, Mohamad G Fakih, Lynn Hadaway, Lisa L Maragakis, Elizabeth Monsees, Shannon Novosad, Naomi P O'Grady, Mark E Rupp, Joshua Wolf, Deborah Yokoe, Leonard A Mermel

2020-Current year OA Pubs

No abstract provided.

Bone Metastases In Non-Small Cell Lung Cancer: A Narrative Review, Brendan J. Knapp, Siddhartha Devarakonda, Ramaswamy Govindan

2020-Current year OA Pubs

Background and Objective: Bone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.

Methods: An …

Efficacy And Safety Of Bempedoic Acid In Patients Not Receiving Statins In Phase 3 Clinical Trials, Ulrich Laufs, Christie M Ballantyne, Maciej Banach, Harold Bays, Alberico L Catapano, P Barton Duell, Anne C Goldberg, Antonio M Gotto, Lawrence A Leiter, Kausik K Ray, Leanne T Bloedon, Diane Macdougall, Yang Zhang, G B John Mancini

2020-Current year OA Pubs

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.

OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.

METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for …

American Society For Transplantation And Cellular Therapy Series: #5-Management Of Clostridioides Difficile Infection In Hematopoietic Cell Transplant Recipients, Carolyn D Alonso, Gabriela Maron, Mini Kamboj, Paul A Carpenter, Arun Gurunathan, Kathleen M Mullane, Erik R Dubberke

2020-Current year OA Pubs

The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E …

Functional Analysis Of A Novel De Novo Variant In Ppp5c Associated With Microcephaly, Seizures, And Developmental Delay, Sara M Fielder, Jill A Rosenfeld, Lindsay C Burrage, Lisa Emrick, Seema Lalani, Ruben Attali, Joshua N Bembenek, Hieu Hoang, Dustin Baldridge, Gary A Silverman, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak

2020-Current year OA Pubs

We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was …

Complexity Of Ballooned Hepatocyte Feature Recognition: Defining A Training Atlas For Artificial Intelligence-Based Imaging In Nafld, Elizabeth M. Brunt, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Histologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in clinical trials and serves as a key regulatory-approved surrogate endpoint for drug efficacy. High inter/intra-observer variation in ballooning measured using the NASH CRN semi-quantitative score has been reported yet no actionable solutions have been proposed.

METHODS: A focused evaluation of hepatocyte ballooning recognition was conducted. Digitized slides were evaluated by 9 internationally recognized expert liver pathologists on 2 separate occasions: each pathologist independently marked every ballooned hepatocyte and later provided an overall non-NASH NAFL/NASH assessment. Interobserver …

Veliparib Plus Carboplatin And Paclitaxel Versus Investigator's Choice Of Standard Chemotherapy In Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis.

MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis …

Anxiety Symptoms Among Patients With Systemic Lupus Erythematosus Persist Over Time And Are Independent Of Sle Disease Activity, Daphne Lew, Xinliang Huang, Sara R Kellahan, Hong Xian, Seth Eisen, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study are to identify patterns of anxiety symptomology over time among patients with systemic lupus erythematosus (SLE) and to assess the longitudinal relationship between SLE disease activity and anxiety symptomology.

METHODS: Longitudinal data from 139 patients with American College of Rheumatology or Systemic Lupus International Collborating Clinic (SLICC)-classified SLE were analyzed. Anxiety symptomology was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress: Anxiety Short Form 8a. SLE disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 (S2K) and S2K Responder Index 50 (S2K RI-50). Group-based trajectory modeling (GBTM) …

Optimization Of Care For Patients With Hereditary Angioedema Living In Rural Areas, Marc A Riedl, Douglas T Johnston, John Anderson, J Allen Meadows, Daniel Soteres, Stephen B Leblanc, H James Wedner, David M Lang

2020-Current year OA Pubs

BACKGROUND: People living in rural areas of the United States experience greater health inequality than individuals residing in urban or suburban locations and encounter several barriers to obtaining optimal health care. Health disparities are compounded for patients with rare diseases such as hereditary angioedema (HAE), an autosomal dominant genetic disorder characterized by recurrent, severe abdominal pain and life-threatening oropharyngeal or laryngeal swelling.

OBJECTIVE: To explore the challenges of managing patients with HAE in rural areas and suggest possible improvements for optimizing care.

DATA SOURCES: PubMed was searched for articles on patient care management, treatment challenges, rural health, and HAE.

STUDY …

Poems Syndrome: Real World Experience In Diagnosis And Systemic Therapy - 108 Patients Multicenter Analysis, Artur Jurczyszyn, Mark Fiala, Ravi Vij, Et Al.

2020-Current year OA Pubs

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present …

Two Cases Of Wolfram Syndrome Who Were Initially Diagnosed With Type 1 Diabetes, Francesca Silvestri, Valeria Tromba, Francesco Costantino, Nila Palaniappan, Fumihiko Urano

2020-Current year OA Pubs

OBJECTIVE: Early diagnosis of syndromic monogenic diabetes allows for proper management and can lead to improved quality of life in the long term. This report aimed to describe 2 genetically confirmed cases of Wolfram syndrome, a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration.

CASE REPORT: A 16-year-old Caucasian male patient and a 25-year-old Caucasian female patient with a history of diabetes mellitus and optic nerve atrophy presented at our medical center. Both patients were initially diagnosed with type 1 diabetes but negative for islet autoantibodies. Their body mass indexes were under 25 …

Hold That Pose: Capturing Cervical Dystonia's Head Deviation Severity From Video, Zheng Zhang, Joel S Perlmutter, Et Al

2020-Current year OA Pubs

OBJECTIVE: Deviated head posture is a defining characteristic of cervical dystonia (CD). Head posture severity is typically quantified with clinical rating scales such as the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Because clinical rating scales are inherently subjective, they are susceptible to variability that reduces their sensitivity as outcome measures. The variability could be circumvented with methods to measure CD head posture objectively. However, previously used objective methods require specialized equipment and have been limited to studies with a small number of cases. The objective of this study was to evaluate a novel software system-the Computational Motor Objective Rater …

Sars-Cov-2 Infection And Covid-19 Outcomes In Rheumatic Diseases: A Systematic Literature Review And Meta-Analysis, Richard Conway, Alfred H J Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients.

METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality …

Cd19 + Cd21lo/Neg Cells Are Increased In Systemic Sclerosis-Associated Interstitial Lung Disease, Erin M Wilfong, Katherine N Vowell, Kaitlyn E Bunn, Elise Rizzi, Narender Annapureddy, Rosemarie B Dudenhofer, April Barnado, Rachel H Bonami, Joyce E Johnson, Leslie J Crofford, Peggy L Kendall

2020-Current year OA Pubs

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017-6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, …

Postviral Gastroparesis Associated With Sars-Cov-2 Infection In A Pediatric Patient, Courtney M. Rusch, Jerome M. Molleston, Matthew F. Glasser, Steven Don, Sakil S. Kulkarni

2020-Current year OA Pubs

Postviral gastroparesis has been described in children, but it has not yet been attributed to SARS-CoV-2 infection. Our case report describes a teenager with abdominal pain, early satiety, and vomiting who likely had an asymptomatic SARS-CoV-2 infection 2 months before presentation. Through investigation of epidemiologic links, antibody testing, and clinical course, it is hypothesized that her significant reduction in gastric emptying was due to postviral gastroparesis secondary to SARS-CoV-2. She was treated with supportive care and prokinetic agents. The patient demonstrated symptom resolution and near normalization of gastric emptying by the time of 1 month follow up.

Ex Vivo Propagation In A Novel 3d High-Throughput Co-Culture System For Multiple Myeloma, Johannes M Waldschmidt, Stefan J Fruttiger, Dagmar Wider, Johannes Jung, Andreas R Thomsen, Tanja N Hartmann, Justus Duyster, Martin J Hug, Kareem A Azab, Manfred Jung, Ralph Wäsch, Monika Engelhardt

2020-Current year OA Pubs

PURPOSE: Multiple myeloma (MM) remains an incurable hematologic malignancy which ultimately develops drug resistance and evades treatment. Despite substantial therapeutic advances over the past years, the clinical failure rate of preclinically promising anti-MM drugs remains substantial. More realistic in vitro models are thus required to better predict clinical efficacy of a preclinically active compound.

METHODS: Here, we report on the establishment of a conical agarose 3D co-culture platform for the preclinical propagation of primary MM cells ex vivo. Cell growth was compared to yet established 2D and liquid overlay systems. MM cell lines (MMCL: RPMI-8226, U266, OPM-2) and primary patient …

A Systematic Review Of Patient-Reported Outcome Measures Patients With Chronic Limb-Threatening Ischemia, Philip Goodney, Samir Shah, Yiyuan David Hu, Bjoern Suckow, Scott Kinlay, David G Armstrong, Patrick Geraghty, Megan Patterson, Matthew Menard, Manesh R Patel, Michael S Conte

2020-Current year OA Pubs

Chronic limb-threatening ischemia (CLTI) causes significant morbidity with profound negative effects on health-related quality of life. As the prevalence of peripheral artery disease and diabetes continue to rise in our aging population, the public health impact of CLTI has escalated. Patient-reported outcome measures (PROMs) have become common and important measures for clinical evaluation in both clinical care and research. PROMs are important for the measurement of clinical effectiveness and cost effectiveness and for shared decision-making on treatment options. However, the PROMs used to describe the experience of patients with CLTI are heterogeneous, incomplete, and lack specific applicability to the underlying …

How Risky Are Risk Factors? An Analysis Of Prenatal Risk Factors In Patients Participating In The Congenital Upper Limb Differences Registry, Tyler Schaeffer, Maria F Canizares, Lindley B Wall, Deborah Bohn, Suzanne Steinman, Julie Samora, Mary Claire Manske, Douglas T Hutchinson, Apurva S Shah, Andrea S Bauer, Could Study Group

2020-Current year OA Pubs

PURPOSE: Risk factors for congenital upper limb differences (CoULDs) are often studied at the general population level. The CoULD registry provides a unique opportunity to study prenatal risk factors within a large patient sample.

METHODS: All patients enrolled between June 2014 and March 2020 in the prospective CoULD registry, a national multicenter database of patients diagnosed with a CoULD, were included in the analysis. We analyzed self-reported, prenatal risk factors, including maternal smoking, alcohol use, recreational drug use, prescription drug use, gestational diabetes mellitus (GDM), and gestational hypertension. The outcome measures included comorbid medical conditions, proximal involvement of limb difference, …

Characteristics, Treatment, And Control Of Hypertension In Public Primary Healthcare Centers In Nigeria: Baseline Results From The Hypertension Treatment In Nigeria Program, Dike B Ojji, Mark D Huffman, Et Al

2020-Current year OA Pubs

BACKGROUND: There are limited data on large-scale, multilevel implementation research studies to improve hypertension diagnosis, treatment, and control rates at the primary healthcare (PHC) level in Africa. We describe the characteristics, treatment, and control rates of patients with hypertension in public PHC centers in the Hypertension Treatment in Nigeria Program.

METHODS: Data were collected from adults at least 18 years at 60 public PHC centers between January 2020 and November 2020. Hypertension treatment rates were calculated at registration and upon completion of the initial visit. Hypertension control rates were calculated based on SBP and DBPs less than 140/90 mmHg. Regression …

Bedside Nurses' Perceptions Of Effective Nurse-Physician Communication In General Medical Units: A Qualitative Study, Hirotaka Kato, Jessica M. Clouser, Preetham Talari, Nikita L. Vundi, Akosua K. Adu, Kishore Karri, Kathy B. Isaacs, Mark V. Williams, Romil Chadha, Jing Li

2020-Current year OA Pubs

Background There is a dearth of research on successful interventions to improve nurse-physician communication (NPC). An important step is identifying what matters to bedside nurses and their perceptions of effective NPC communications and actions. Methods We conducted three focus groups with a total of 19 medical unit nurses across two hospitals in one academic medical center in the United States. Using a convenience sampling strategy, five to eight nurses voluntarily participated in each focus group. The recording was transcribed verbatim and two independent coders performed coding and resolved any discrepancies in codes. Qualitative content analysis was pursued to identify themes …

Physician-Scientists In The United States At 2020: Trends And Concerns, Howard H Garrison, Timothy J Ley

2020-Current year OA Pubs

Physician-scientists comprise a unique and valuable part of the biomedical workforce, but for decades there has been concern about the number of physicians actively engaged in research. Reports have outlined the challenges facing physician-scientists, and programs have been initiated to encourage and facilitate research careers for medically trained scientists. Many of these initiatives have demonstrated successful outcomes, but there has not been a recent summary of the impact of the past decade of effort. This report compiles available data from surveys of medical education and physician research participation to assess changes in the physician-scientist workforce from 2011-2020. Several trends are …

Applying Diagnosis Support Systems In Electronic Health Records To Identify Wild-Type Transthyretin Amyloid Cardiomyopathy Risk, Connor Willis, Alexandre H Watanabe, Justin Hughes, Kimberly Nolen, Jason O'Meara, Alexander Schepart, Marianna Bruno, Joseph Biskupiak, Kensaku Kawamoto, Nawar Shara, Thomas Kannampallil

2020-Current year OA Pubs

No abstract provided.

Bisphenol A Exposure Induces Sensory Processing Deficits In Larval Zebrafish During Neurodevelopment, Courtney Scaramella, Joseph B Alzagatiti, Christopher Creighton, Samandeep Mankatala, Fernando Licea, Gabriel M Winter, Jasmine Emtage, Joseph R Wisnieski, Luis Salazar, Anjum Hussain, Faith M Lee, Asma Mammootty, Niyaza Mammootty, Andrew Aldujaili, Kristine A Runnberg, Daniela Hernandez, Trevor Zimmerman-Thompson, Rikhil Makwana, Julien Rouvere, Zahra Tahmasebi, Gohar Zavradyan, Christopher S Campbell, Meghna Komaranchath, Javier Carmona, Jennifer Trevitt, David Glanzman, Adam C Roberts

2020-Current year OA Pubs

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Physician Perceptions And Use Of Reduced-Dose Direct Oral Anticoagulants For Extended Phase Venous Thromboembolism Treatment, Danielle Groat, Karlyn A Martin, Rachel P Rosovsky, Kristen M Sanfilippo, Manila Gaddh, Lisa Baumann Kreuziger, M Elaine Eyster, Scott C Woller, Venous Thromboembolism Network Us (Venus) Vte Treatment, Anticoagulation Management Group

2020-Current year OA Pubs

Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction.

Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment.

Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups. …

Cardiac Mesenchymal Stem Cells Promote Fibrosis And Remodeling In Heart Failure: Role Of Pdgf Signaling, Tariq Hamid, Yuanyuan Xu, Mohamed Ameen Ismahil, Gregg Rokosh, Miki Jinno, Guihua Zhou, Qiongxin Wang, Sumanth D. Prabhu

2020-Current year OA Pubs

Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post-myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post-myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC-myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor …

Cerebrospinal Fluid Neurofilament Light Chain Is A Marker Of Aging And White Matter Damage, Karin L Meeker, Omar H Butt, Brian A Gordon, Anne M Fagan, Suzanne E Schindler, John C Morris, Tammie L S Benzinger, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain (NfL) reflects neuro-axonal damage and is increasingly used to evaluate disease progression across neurological conditions including Alzheimer disease (AD). However, it is unknown how NfL relates to specific types of brain tissue. We sought to determine whether CSF NfL is more strongly associated with total gray matter, white matter, or white matter hyperintensity (WMH) volume, and to quantify the relative importance of brain tissue volume, age, and AD marker status (i.e., APOE genotype, brain amyloidosis, tauopathy, and cognitive status) in predicting CSF NfL.

METHODS: 419 participants (Clinical Dementia Rating [CDR] Scale > 0, N …

The Clinical Cell-Cycle Risk (Ccr) Score Is Associated With Metastasis After Radiation Therapy And Provides Guidance On When To Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation, Jonathan Tward, Hiram A. Gay, Jeff Michalski, Et Al.

2020-Current year OA Pubs

PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT).

METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). …

Impact Of Consensus Guidelines For Breast-Conserving Surgery In Patients With Ductal Carcinoma In Situ, Abigail Tremelling, Rebecca L Aft, Amy E Cyr, William E Gillanders, Katherine Glover-Collins, Virginia Herrmann, Julie A Margenthaler

2020-Current year OA Pubs

BACKGROUND: Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices.

AIMS: To evaluate the impact of this consensus guideline on our institutional practices.

METHODS: We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before …

Endogenous Metabolic Markers For Predicting The Activity Of Dihydropyrimidine Dehydrogenase, Jihyun Kang, Andrew Hyoungjin Kim, Inseung Jeon, Jaeseong Oh, In-Jin Jang, Seunghwan Lee, Joo-Youn Cho

2020-Current year OA Pubs

Five-fluorouracil (5-FU) is a chemotherapeutic agent that is mainly metabolized by the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5-FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into …

Non-Functional Pancreatic Neuroendocrine Tumours: Atrx/Daxx And Alternative Lengthening Of Telomeres (Alt) Are Prognostically Independent From Arx/Pdx1 Expression And Tumour Size, Wenzel M Hackeng, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.

DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional …