Digital Commons Network^™

Multimorbidity Phenotypes In Ankylosing Spondylitis And Their Association With Disease Activity And Functional Impairment: Data From The Prospective Study Of Outcomes In Ankylosing Spondylitis Cohort, Paras Karmacharya, Cynthia S Crowson, Ryan J Lennon, Dilli Poudel, John M Davis, Alexis Ogdie, Jean W Liew, Michael M Ward, Mariko Ishimori, Michael H Weisman, Matthew A Brown, Mohammad H Rahbar, Mark C Hwang, John D Reveille, Lianne S Gensler

Faculty, Staff and Student Publications

Objectives: To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS).

Methods: Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method …

The Role Of Palliative Care Consultation In Withdrawal Of Life-Sustaining Treatment Among Icu Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (Vv-Ecmo): A Retrospective Case-Control Study, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

The Role Of Peroxisome Proliferator-Activated Receptors In The Development And Physiology Of Gametes And Preimplantation Embryos, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …

Culturally Relevant Africultural Coping Moderates The Association Between Discrimination And Antiretroviral Adherence Among Sexual Minority Black Americans Living With Hiv., Glenn J. Wagner, Laura M. Bogart, David J. Klein, Sean J. Lawrence, Kathy Goggin, Mahlet Gizaw, Matt G. Mutchler

Manuscripts, Articles, Book Chapters and Other Papers

Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses …

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex, Ahmed Chahdi, Carolina Jorgez, Abhishek Seth

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham

Faculty, Staff and Students Publications

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs).

Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).

Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the …

Patterns Of Self-Care Decision-Making And Associated Factors: A Cross-Sectional Observational Study, Christopher S Lee, Kenneth E Freedland, Tiny Jaarsma, Anna Strömberg, Ercole Vellone, Shayleigh Dickson Page, Heleen Westland, Sara Pettersson, Michelle Van Rijn, Subhash Aryal, Andrew Belfiglio, Douglas Wiebe, Barbara Riegel

2020-Current year OA Pubs

OBJECTIVE: The aim of this study was to identify for the first time patterns of self-care decision-making (i.e. the extent to which participants viewed contextual factors influencing decisions about symptoms) and associated factors among community-dwelling adults with chronic illness.

METHODS: This was a secondary analysis of data collected during the development and psychometric evaluation of the 27-item Self-Care Decisions Inventory that is based on Naturalistic Decision-Making (n = 430, average age = 54.9 ± 16.2 years, 70.2 % female, 87.0 % Caucasian, average number of chronic conditions = 3.6 ± 2.8). Latent class mixture modeling was used to identify patterns …

The Role Of Family Accommodation In Child Posttraumatic Stress Symptoms And Functional Impairment In The Context Of Cognitive Behavioral Therapy, Ogechi Cynthia Onyeka, Samuel D Spencer, Alison Salloum, Katie Jiannetto, Eric A Storch

Faculty, Staff and Students Publications

BACKGROUND: Caregiver behaviors such as family accommodation (FA) are negatively reinforced by reduced distress in the short term, but ultimately maintain symptoms. It is important to explore the role of FA on symptoms and impairment. The current study examined the relationship among FA, posttraumatic stress symptoms (PTSS), and functional impairment in a sample of children and their caregivers who completed trauma treatment.

METHOD: Participants included 183 children and their caregivers (M age = 7.89; 55.19 % female; 73.22 % non-Hispanic; 51.37 % White). Data consisted of parent-reported measures collected at baseline, post-treatment, and 12-month follow-up from a randomized control trial …

Novel Hemizygous Single-Nucleotide Duplication In Rpgr In A Patient With Retinal Dystrophy And Sensorineural Hearing Loss, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Nichole Owen, Richard A Lewis, Lisa Saba, Texome Project, Michael F Wangler, Sandesh Nagamani

Duncan NRI Faculty and Staff Publications

Background: The RPGR gene has been associated with X-linked cone-rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel-based testing and thus genome-wide tests such as ES may be required for accurate diagnosis.

Methods: The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care.

Results: A 58-year-old male presented with retinitis pigmentosa, sensorineural hearing loss, and …

Mapping Gray And White Matter Volume Abnormalities In Early-Onset Psychosis: An Enigma Multicenter Voxel-Based Morphometry Study, Shuqing Si, Anbreen Bi, Zhaoying Yu, Cheryl See, Sinead Kelly, Sonia Ambrogi, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Michael Berk, Josefina Castro-Fornieles, Benedicto Crespo-Facorro, Jacob J Crouse, Covadonga M Díaz-Caneja, Anne-Kathrin Fett, Adriana Fortea, Sophia Frangou, Benjamin I Goldstein, Ian B Hickie, Joost Janssen, Kody G Kennedy, Lydia Krabbendam, Marinos Kyriakopoulos, Bradley J Macintosh, Pedro Morgado, Stener Nerland, Saül Pascual-Diaz, Maria Picó-Pérez, Fabrizio Piras, Bjørn Rishovd Rund, Elena De La Serna, Gianfranco Spalletta, Gisela Sugranyes, Chao Suo, Diana Tordesillas-Gutiérrez, Daniela Vecchio, Joaquim Radua, Philip Mcguire, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Claudia Barth, Ingrid Agartz, Anthony James, Matthew J Kempton

Faculty, Staff and Students Publications

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Oral Toxicities Associated With Immune Checkpoint Inhibitors: Meta-Analyses Of Clinical Trials, Akanksha Srivastava, Graciela M Nogueras-Gonzalez, Yimin Geng, Jasdev Singh, Jeffrey N Myers, Yisheng Li, Mark S Chambers

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using …

Activation Of Testosterone-Androgen Receptor Mediates Cerebrovascular Protection By Photobiomodulation Treatment In Photothrombosis-Induced Stroke Rats, Yu Feng, Zhihai Huang, Xiaohui Ma, Xuemei Zong, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin, Michael R Hamblin, Quanguang Zhang

Faculty, Staff and Student Publications

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown.

METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with …

Phase I Study Of Sapanisertib (Cb-228/Tak-228/Mln0128) In Combination With Ziv-Aflibercept In Patients With Advanced Solid Tumors, Niamh Coleman, Bettzy Stephen, Siqing Fu, Daniel Karp, Vivek Subbiah, Jordi Rodon Ahnert, Sarina A Piha-Paul, John Wright, Senait N Fessahaye, Fengying Ouyang, Bulent Yilmaz, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Sapanisertib is a potent ATP-competitive, dual inhibitor of mTORC1/2. Ziv-aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF-1α inhibition in combination with anti-angiogenic therapy is a promising anti-tumor strategy. This Phase 1 dose-escalation/expansion study assessed safety/ tolerability of sapanisertib in combination with ziv-aflibercept in advanced solid tumors.

METHODS: Fifty-five patients with heavily pre-treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.

RESULTS: Fifty-five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age …

Allogeneic Stem Cell Therapy For Acute Ischemic Stroke: The Phase 2/3 Treasure Randomized Clinical Trial, Kiyohiro Houkin, Toshiya Osanai, Shinichiro Uchiyama, Kazuo Minematsu, Akihiko Taguchi, Katsuhiko Maruichi, Yoshimasa Niiya, Katsuyuki Asaoka, Yoshihiro Kuga, Katsumi Takizawa, Koichi Haraguchi, Shinichi Yoshimura, Kazumi Kimura, Koji Tokunaga, Atsuo Aoyama, Fusao Ikawa, Chikanori Inenaga, Tatsuya Abe, Atsushi Tominaga, Shinichi Takahashi, Kohsuke Kudo, Miki Fujimura, Taku Sugiyama, Masaki Ito, Masahito Kawabori, David C Hess, Sean I Savitz, Teruyuki Hirano

Faculty, Staff and Student Publications

IMPORTANCE: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke.

OBJECTIVE: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset.

DESIGN, SETTING, AND PARTICIPANTS: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were …

Characteristics And Outcomes Of Patients With Multiple Myeloma Who Developed Therapy-Related Acute Myeloid Leukemia And Myelodysplastic Syndrome After Autologous Cell Transplantation, Fevzi F Yalniz, Uri Greenbaum, Oren Pasvolsky, Denái R Milton, Rashmi Kanagal-Shamanna, Jeremy Ramdial, Samer Srour, Rohtesh Mehta, Amin Alousi, Uday R Popat, Yago Nieto, Partow Kebriaei, Gheath Al-Atrash, Betul Oran, Chitra Hosing, Sairah Ahmed, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Qaiser Bashir

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1 January and 31 December 2018 and later developed t-MDS/AML. Among the 2982 patients who underwent at least 1 Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n = 52; AML, n = 3). The median age at t-MDS/AML diagnosis was 66 years (range 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis …

Isolated Abducens Nerve Palsy: A Rare Manifestation Of Recurrent Extramedullary Myeloma, Neal Joshi, Joy Li, Ajit Karambelkar, Payton Boere

Jefferson Hospital Staff Papers and Presentations

Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas may manifest in central nervous system involvement as cranial nerve palsies. Cranial nerve six palsy is the most common in cases of malignancy. However, isolated abducens palsy presenting as multiple myeloma recurrence is very uncommon. Here, we detail two cases in which intracranial plasmacytoma lesions were present within the region of the Dorello canal, resulting in acute isolated unilateral diplopia from disease recurrence in the absence of systemic marrow involvement.

The Mef2c Gene Dose-Dependently Controls Hippocampal Neurogenesis And The Expression Of Autism-Like Behaviors, Sreetama Basu, Eun Jeoung Ro, Zhi Liu, Hyunjung Kim, Aubrey Bennett, Seungwoo Kang, Hoonkyo Suh

The Brown Foundation: Institute of Molecular Medicine

Mutations in the activity-dependent transcription factor MEF2C have been associated with several neuropsychiatric disorders. Among these, autism spectrum disorder (ASD)-related behavioral deficits are manifested. Multiple animal models that harbor mutations in Mef2c have provided compelling evidence that Mef2c is indeed an ASD gene. However, studies in mice with germline or global brain knock-out of Mef2c are limited in their ability to identify the precise neural substrates and cell types that are required for the expression of Mef2c-mediated ASD behaviors. Given the role of hippocampal neurogenesis in cognitive and social behaviors, in this study we aimed to investigate the role …

Cardiovascular Health Assessment In Routine Cancer Follow-Up In Community Settings: Survivor Risk Awareness And Perspectives, Kathryn E Weaver, Emily V Dressler, Sydney Smith, Chandylen L Nightingale, Heidi D Klepin, Simon Craddock Lee, Brian J Wells, W Gregory Hundley, Joseph A Demari, Sarah N Price, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters.

METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including …

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

Mental Imagery To Reduce Alcohol-Related Harm In Patients With Alcohol Use Disorder And Alcohol-Related Liver Damage: The Mirage Randomised Pilot Trial Results, Ashwin Dhanda, Jackie Andrade, Hannah Allende, Victoria Allgar, Matthew Bailey, Lynne Callaghan, Laura Cocking, Elizabeth Goodwin, Annie Hawton, Christopher Hayward, Ben Hudson, Wendy Ingram, Alison Jeffery, Angela King, Victoria Lavers, Joe Lomax, C Anne Mccune, Crispin Musicha, Richard Parker, Christopher Rollinson, Jonny Wilks, E Siobhan Creanor

Peninsula Medical School

OBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD.

DESIGN: Participants were randomised to TAU (a single session …

Mosaic Loss Of Y Chromosome Is Associated With Aging And Epithelial Injury In Chronic Kidney Disease, Parker C Wilson, Amit Verma, Yasuhiro Yoshimura, Yoshiharu Muto, Haikuo Li, Nicole P Malvin, Eryn E Dixon, Benjamin D Humphreys

2020-Current year OA Pubs

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease.

RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of …

Analysis Of Anemia And Iron Supplementation Among Glioblastoma Patients Reveals Sex-Biased Association Between Anemia And Survival, Ganesh Shenoy, Becky Slagle-Webb, Chachrit Khunsriraksakul, Bhavyata Pandya Shesh, Jingqin Luo, Vladimir Khristov, Nataliya Smith, Alireza Mansouri, Brad E Zacharia, Sheldon Holder, Justin D Lathia, Jill S Barnholtz-Sloan, James R Connor

2020-Current year OA Pubs

The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR …

Longitudinal Varying Coefficient Single-Index Model With Censored Covariates, Shikun Wang, Jing Ning, Ying Xu, Ya-Chen Tina Shih, Yu Shen, Liang Li

Faculty, Staff and Student Publications

It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a …

Association Of Genetic Variation In Col11a1 With Adolescent Idiopathic Scoliosis, Hao Yu, Lilian Antunes, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the

Simultaneous Detection Of Helicobacter Pylori Infection Comparing Between White Light And Image-Enhanced Endoscopy, Boonyaorn Chatrangsun, Natsuda Aumpan, Bubpha Pornthisarn, Soonthorn Chonprasertsuk, Sith Siramolpiwat, Patommatat Bhanthumkomol, Pongjarat Nunanan, Navapan Issariyakulkarn, Varocha Mahachai, Yoshio Yamaoka, Ratha-Korn Vilaichone

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection.

METHODS: This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand …