Medicine and Health Sciences Commons^™

Clonal Hematopoiesis Is Associated With Higher Risk Of Stroke, Romit Bhattacharya, Seyedeh M Zekavat, Jeffrey Haessler, Myriam Fornage, Laura Raffield, Md Mesbah Uddin, Alexander G Bick, Abhishek Niroula, Bing Yu, Christopher Gibson, Gabriel Griffin, Alanna C Morrison, Bruce M Psaty, William T Longstreth, Joshua C Bis, Stephen S Rich, Jerome I Rotter, Russell P Tracy, Adolfo Correa, Sudha Seshadri, Andrew Johnson, Jason M Collins, Kathleen M Hayden, Tracy E Madsen, Christie M Ballantyne, Siddhartha Jaiswal, Benjamin L Ebert, Charles Kooperberg, Joann E Manson, Eric A Whitsel, Nhlbi Trans-Omics For Precision Medicine Program, Pradeep Natarajan, Alexander P Reiner

Faculty, Staff and Student Publications

Background and purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.

Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Judith Trotman, Paula Marlton, Javier Munoz, Patrick Johnston, David Simpson, Jennifer C Stern, Radha Prathikanti, Kenneth Wu, William Novotny, Jane Huang, Constantine S Tam

Faculty, Staff and Student Publications

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response …

Interleukin-6 Blockade Abrogates Immunotherapy Toxicity And Promotes Tumor Immunity, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Underutilization Of Endovascular Therapy In Black Patients With Ischemic Stroke: An Analysis Of State And Nationwide Cohorts, Youngran Kim, Anjail Sharrief, Min Ji Kwak, Swapnil Khose, Rania Abdelkhaleq, Sergio Salazar-Marioni, Guo-Qiang Zhang, Sunil A Sheth

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is a very effective treatment but relies on specialized capabilities that are not available in every hospital where acute ischemic stroke is treated. Here, we assess whether access to and utilization of this therapy has extended uniformly across racial and ethnic groups.

METHODS: We conducted a retrospective, population-based study using the 2019 Texas Inpatient Public Use Data File. Acute ischemic stroke cases and EVT use were identified using the

RESULTS: Among 40 814 acute ischemic stroke cases in Texas in 2019, 54% were White, 17% Black, and 21% Hispanic. Black patients had similar admissions …

Perioperative Nivolumab Monotherapy Versus Nivolumab Plus Ipilimumab In Resectable Hepatocellular Carcinoma: A Randomised, Open-Label, Phase 2 Trial, Ahmed Omar Kaseb, Elshad Hasanov, Hop Sanderson Tran Cao, Lianchun Xiao, Jean-Nicolas Vauthey, Sunyoung S Lee, Betul Gok Yavuz, Yehia I Mohamed, Aliya Qayyum, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Courtney Nicholas, Jing Jing Sun, Kanwal Pratap Singh Raghav, Asif Rashid, Kristen Carter, Yun Shin Chun, Ching-Wei David Tzeng, Divya Sakamuri, Li Xu, Ryan Sun, Vittorio Cristini, Laura Beretta, James C Yao, Robert A Wolff, James Patrick Allison, Padmanee Sharma

Faculty, Staff and Student Publications

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma.

METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 …

Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke

Open Access Publications

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through …

Comparison Of Performance Of Psychiatrists Vs Other Outpatient Physicians In The 2020 Us Medicare Merit-Based Incentive Payment System, Andrew C Qi, Karen E Joynt Maddox, Laura J Bierut, Kenton J Johnston

2020-Current year OA Pubs

Importance: Medicare's Merit-Based Incentive Payment System (MIPS) is a new, mandatory, outpatient value-based payment program that ties reimbursement to performance on cost and quality measures for many US clinicians. However, it is currently unknown how the program measures the performance of psychiatrists, who often treat a different patient case mix with different clinical considerations than do other outpatient clinicians.

Objective: To compare performance scores and value-based reimbursement for psychiatrists vs other outpatient physicians in the 2020 MIPS.

Design Setting and Participants: In this cross-sectional study, the Centers for Medicare & Medicaid Services Provider Data Catalog was used to identify outpatient …

Health-Related Quality Of Life, Symptoms, And Tolerability Of Loncastuximab Tesirine In Patients With Relapsed Or Refractory Diffuse Large B-Cell Lymphoma, Alexander Spira, Xiaolei Zhou, Lei Chen, Ari Gnanasakthy, Luqiang Wang, David Ungar, Rafael Curiel, Laura Liao, John Radford, Brad Kahl

2020-Current year OA Pubs

BACKGROUND: Loncastuximab tesirine has shown antitumor activity with an acceptable toxicity profile in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were relapsed or refractory after ≥2 prior therapies, including activity in patients with high-risk disease characteristics. This analysis examined health-related quality of life (HRQoL), symptoms, and tolerability in patients receiving loncastuximab tesirine for relapsed or refractory DLBCL.

PATIENTS AND METHODS: The single-arm, open-label phase II LOTIS-2 study (ADCT-402-201; NCT03589469) enrolled 145 patients aged ≥18 years. Patients received loncastuximab tesirine as a 30-minute intravenous infusion on day 1 of each 3-week treatment cycle. Patient-reported outcomes were measured …

Risk Of Intracranial Haemorrhage And Ischaemic Stroke After Convexity Subarachnoid Haemorrhage In Cerebral Amyloid Angiopathy: International Individual Patient Data Pooled Analysis, Isabel Charlotte Hostettler, Diane Aum, Gregory Joseph Zipfel, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).

METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.

RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each …

Comprehensive Analysis Of Alternative Splicing In Gastric Cancer Identifies Epithelial-Mesenchymal Transition Subtypes Associated With Survival., Yukyung Jun, Yun-Suhk Suh, Sunghee Park, Jieun Lee, Jong-Il Kim, Sanghyuk Lee, Wan-Ping Lee, Olga Anczuków, Han-Kwang Yang, Charles Lee

Faculty Research 2022

Alternatively spliced RNA isoforms are a hallmark of tumors, but their nature, prevalence, and clinical implications in gastric cancer have not been comprehensively characterized. We systematically profiled the splicing landscape of 83 gastric tumors and matched normal mucosa, identifying and experimentally validating eight splicing events that can classify all gastric cancers into three subtypes: epithelial-splicing (EpiS), mesenchymal-splicing (MesS), and hybrid-splicing. These subtypes were associated with distinct molecular signatures and epithelial-mesenchymal transition markers. Subtype-specific splicing events were enriched in motifs for splicing factors RBM24 and ESRP1, which were upregulated in MesS and EpiS tumors, respectively. A simple classifier based only on …

Sars-Cov-2 Infection Increases Risk Of Acute Kidney Injury In A Bimodal Age Distribution, Erica C Bjornstad, Gary Cutter, Pramod Guru, Shina Menon, Isabella Aldana, Scott House, Nancy M Tofil, Catherine A St Hill, Yasir Tarabichi, Valerie M Banner-Goodspeed, Amy B Christie, Surapaneni Krishna Mohan, Devang Sanghavi, Jarrod M Mosier, Girish Vadgaonkar, Allan J Walkey, Rahul Kashyap, Vishakha K Kumar, Vikas Bansal, Karen Boman, Mayank Sharma, Marija Bogojevic, Neha Deo, Lynn Retford, Ognjen Gajic, Katja M Gist, Sccm Discovery Virus Investigators Group

Faculty, Staff and Students Publications

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern.

METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, …

Intracranial Internal Carotid Artery Calcification Is Not Predictive Of Future Cognitive Decline, Farzaneh Rahmani, Marina Nguyen, Charles D Chen, Nicole Mckay, Aylin Dincer, Nelly Joseph-Mathurin, Gengsheng Chen, Jingxia Liu, Hilary L P Orlowski, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia.

METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to …

Single-Agent Mosunetuzumab Shows Durable Complete Responses In Patients With Relapsed Or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study, Lihua E Budde, Nancy L Bartlett, Et Al

2020-Current year OA Pubs

PURPOSE: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).

METHODS: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 …

Do Formulation And Dose Of Long-Term Opioid Therapy Contribute To Risk Of Adverse Events Among Older Adults?, Monika Salkar, Sujith Ramachandran, John P. Bentley, Ike Eriator

Faculty and Student Publications

Background: Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. Objective: To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. Design: Nested case-control study. Participants: Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day …

Examining Rural-Urban Differences In Fatalism And Information Overload: Data From 12 Nci-Designated Cancer Centers, Jakob D Jensen, Jackilen Shannon, Ronaldo Iachan, Yangyang Deng, Sunny Jung Kim, Wendy Demark-Wahnefried, Babalola Faseru, Electra D Paskett, Jinxiang Hu, Robin C Vanderpool, Deann Lazovich, Jason A Mendoza, Sanjay Shete, Linda B Robertson, Rajesh Balkrishnan, Katherine J Briant, Benjamin Haaland, David A Haggstrom, Bernard F Fuemmeler, Rural Workgroup Of The Population Health Assessment In Cancer Center Catchment Areas Consortium

Faculty, Staff and Student Publications

BACKGROUND: Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.

METHODS: Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (

RESULTS: Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …

Efficacy And Safety Of Covid-19 Convalescent Plasma In Hospitalized Patients: A Randomized Clinical Trial, Mila B Ortigoza, Hyunah Yoon, Keith S Goldfeld, Andrea B Troxel, Johanna P Daily, Yinxiang Wu, Yi Li, Danni Wu, Gia F Cobb, Gillian Baptiste, Mary O'Keeffe, Marilou O Corpuz, Luis Ostrosky-Zeichner, Amee Amin, Ioannis M Zacharioudakis, Dushyantha T Jayaweera, Yanyun Wu, Julie V Philley, Megan S Devine, Mahalia S Desruisseaux, Alessandro D Santin, Shweta Anjan, Reeba Mathew, Bela Patel, Masayuki Nigo, Rabi Upadhyay, Tania Kupferman, Andrew N Dentino, Rahul Nanchal, Christian A Merlo, David N Hager, Kartik Chandran, Jonathan R Lai, Johanna Rivera, Chowdhury R Bikash, Gorka Lasso, Timothy P Hilbert, Monika Paroder, Andrea A Asencio, Mengling Liu, Eva Petkova, Alexander Bragat, Reza Shaker, David D Mcpherson, Ralph L Sacco, Marla J Keller, Corita R Grudzen, Judith S Hochman, Liise-Anne Pirofski, Lalitha Parameswaran, Anthony T Corcoran, Abhinav Rohatgi, Marta W Wronska, Xinyuan Wu, Ranjini Srinivasan, Fang-Ming Deng, Thomas D Filardo, Jay Pendse, Simone B Blaser, Olga Whyte, Jacqueline M Gallagher, Ololade E Thomas, Danibel Ramos, Caroline L Sturm-Reganato, Charlotte C Fong, Ivy M Daus, Arianne Gisselle Payoen, Joseph T Chiofolo, Mark T Friedman, Ding Wen Wu, Jessica L Jacobson, Jeffrey G Schneider, Uzma N Sarwar, Henry E Wang, Ryan M Huebinger, Goutham Dronavalli, Yu Bai, Carolyn Z Grimes, Karen W Eldin, Virginia E Umana, Jessica G Martin, Timothy R Heath, Fatimah O Bello, Daru Lane Ransford, Maudry Laurent-Rolle, Sheela V Shenoi, Oscar Bate Akide-Ndunge, Bipin Thapa, Jennifer L Peterson, Kelly Knauf, Shivani U Patel, Laura L Cheney, Christopher A Tormey, Jeanne E Hendrickson

Faculty, Staff and Student Publications

IMPORTANCE: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.

OBJECTIVE: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.

DESIGN, SETTING, AND PARTICIPANTS: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation.

INTERVENTIONS: A unit of …

Evaluating Older Adults With Cognitive Dysfunction: A Qualitative Study With Emergency Clinicians, Anita N Chary, Noelle Castilla-Ojo, Christopher Joshi, Ilianna Santangelo, Christopher R Carpenter, Kei Ouchi, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

BACKGROUND: Evaluating older adults with cognitive dysfunction in emergency departments (EDs) requires obtaining collateral information from sources other than the patient. Understanding the challenges emergency clinicians face in obtaining collateral information can inform development of interventions to improve geriatric emergency care and, more specifically, detection of ED delirium. The objective was to understand emergency clinicians' experiences obtaining collateral information on older adults with cognitive dysfunction, both before and during the COVID-19 pandemic.

METHODS: From February to May 2021, we conducted semi-structured interviews with a purposive sample of 22 emergency physicians and advanced practice providers from two urban academic hospitals and …

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …

Comparative Performance Of Risk Prediction Models For Hepatitis B-Related Hepatocellular Carcinoma In The United States, Hyun-Seok Kim, Xian Yu, Jennifer Kramer, Aaron P Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

METHODS: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

RESULTS: Of 3,101 patients …

Age-Associated Gut Dysbiosis, Marked By Loss Of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites In Older People Living With Hiv, Smita Ghare, Richa Singhal, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Andrea Reyes-Vega, Dushan Ghooray, Craig J Mcclain, Kristi Hoffman, Joseph Petrosino, Kendall Bryant, Varan Govind, Ronald Cohen, Robert L Cook, Shirish Barve

Faculty, Staff and Students Publications

BACKGROUND: Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined.

METHODS: Older people living with HIV infection (PLWH, aged 50-70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome …

Mental Health In The Uk Biobank: A Roadmap To Self-Report Measures And Neuroimaging Correlates, Rosie K Dutt, Kayla Hannon, Ty O Easley, Joseph C Griffis, Wei Zhang, Janine D Bijsterbosch

2020-Current year OA Pubs

The UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in …

Rpop: Robust Pet-Only Processing Of Community Acquired Heterogeneous Amyloid-Pet Data, Leonardo Iaccarino, Renaud La Joie, Robert Koeppe, Barry A Siegel, Bruce E Hillner, Constantine Gatsonis, Rachel A Whitmer, Maria C Carrillo, Charles Apgar, Monica R Camacho, Rachel Nosheny, Gil D Rabinovici, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (

Impact Of Frontline Treatment Approach On Outcomes In Patients With Secondary Aml With Prior Hypomethylating Agent Exposure, Nicholas J Short, Sangeetha Venugopal, Wei Qiao, Tapan M Kadia, Farhad Ravandi, Walid Macaron, Courtney D Dinardo, Naval Daver, Marina Konopleva, Gautam Borthakur, Elizabeth J Shpall, Uday Popat, Richard E Champlin, Rohtesh Mehta, Gheath Al-Atrash, Betul Oran, Elias Jabbour, Guillermo Garcia-Manero, Ghayas C Issa, Guillermo Montalban-Bravo, Musa Yilmaz, Abhishek Maiti, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Treated secondary acute myeloid leukemia (ts-AML)-i.e., AML arising from a previously treated antecedent hematologic disorder-is associated with very poor outcomes. The optimal frontline treatment regimen for these patients is uncertain.

METHODS: We retrospectively analyzed 562 patients who developed AML from preceding myelodysplastic syndrome or chronic myelomonocytic leukemia for which they had received a hypomethylating agent (HMA). Patients with ts-AML were stratified by frontline AML treatment with intensive chemotherapy (IC, n = 271), low-intensity therapy (LIT) without venetoclax (n = 237), or HMA plus venetoclax (n = 54).

RESULTS: Compared with IC or LIT without venetoclax, HMA plus venetoclax resulted …

Efficacy And Safety Of Enasidenib And Azacitidine Combination In Patients With Idh2 Mutated Acute Myeloid Leukemia And Not Eligible For Intensive Chemotherapy, Sangeetha Venugopal, Koichi Takahashi, Naval Daver, Abhishek Maiti, Gautam Borthakur, Sanam Loghavi, Nicholas J Short, Maro Ohanian, Lucia Masarova, Ghayas Issa, Xuemei Wang, Bueso-Ramos Carlos, Musa Yilmaz, Tapan Kadia, Michael Andreeff, Farhad Ravandi, Marina Konopleva, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Preclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH2 mutated acute myeloid leukemia (IDH2mutAML). This open label phase II trial enrolled patients (pts) with documented IDH2mutAML. All patients received AZA 75 mg/m2/d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24-88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The …

Single-Cell Multi-Omics Reveals Dyssynchrony Of The Innate And Adaptive Immune System In Progressive Covid-19., Avraham Unterman, Tomokazu S Sumida, Nima Nouri, Xiting Yan, Amy Y Zhao, Victor Gasque, Jonas C Schupp, Hiromitsu Asashima, Yunqing Liu, Carlos Cosme, Wenxuan Deng, Ming Chen, Micha Sam Brickman Raredon, Kenneth B Hoehn, Guilin Wang, Zuoheng Wang, Giuseppe Deiuliis, Neal G Ravindra, Ningshan Li, Christopher Castaldi, Patrick Wong, John Fournier, Santos Bermejo, Lokesh Sharma, Arnau Casanovas-Massana, Chantal B F Vogels, Anne L Wyllie, Nathan D Grubaugh, Anthony Melillo, Hailong Meng, Yan Stein, Maksym Minasyan, Subhasis Mohanty, William E Ruff, Inessa Cohen, Khadir Raddassi, Laura E Niklason, Albert I Ko, Ruth R Montgomery, Shelli F Farhadian, Akiko Iwasaki, Albert C Shaw, David Van Dijk, Hongyu Zhao, Steven H Kleinstein, David A Hafler, Naftali Kaminski, Charles S Dela Cruz

Faculty Research 2022

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A

Effect Of P2y12 Inhibitors On Survival Free Of Organ Support Among Non-Critically Ill Hospitalized Patients With Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Lucy Z Kornblith, Michelle N Gong, Harmony R Reynolds, Mary Cushman, Yu Cheng, Bryan J Mcverry, Keri S Kim, Renato D Lopes, Bassel Atassi, Scott Berry, Grant Bochicchio, Murillo De Oliveira Antunes, Michael E Farkouh, Yonatan Greenstein, Erinn M Hade, Kristin Hudock, Robert Hyzy, Pooja Khatri, Andrei Kindzelski, Bridget-Anne Kirwan, Lisa Baumann Kreuziger, Patrick R Lawler, Eric Leifer, Jose Lopez-Sendon Moreno, Jose Lopez-Sendon, James F Luther, Lilia Nigro Maia, John Quigley, Robert Sherwin, Lana Wahid, Jennifer Wilson, Judith S Hochman, Matthew D Neal, Activ-4a Investigators

Faculty, Staff and Students Publications

IMPORTANCE: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.

OBJECTIVE: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021.

INTERVENTIONS: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = …

Clonal Hematopoiesis Mutations In Patients With Lung Cancer Are Associated With Lung Cancer Risk Factors, Wei Hong, Ang Li, Yanhong Liu, Xiangjun Xiao, David C Christiani, Rayjean J Hung, James Mckay, John Field, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH) is a phenomenon caused by expansion of white blood cells descended from a single hematopoietic stem cell. While CH can be associated with leukemia and some solid tumors, the relationship between CH and lung cancer remains largely unknown. To help clarify this relationship, we analyzed whole-exome sequencing (WES) data from 1,958 lung cancer cases and controls. Potential CH mutations were identified by a set of hierarchical filtering criteria in different exonic regions, and the associations between the number of CH mutations and clinical traits were investigated. Family history of lung cancer (FHLC) may exert diverse influences on …

Droplet Precautions On-Site (Drops) During The Influenza Season 2018/2019: A Possible Alternative To Single Room Isolation For Respiratory Viral Infections, Michèle Birrer, Martin Perrig, Fabienne Hobi, Christina Gfeller, Andrew Atkinson, Martin Egger, Corinne Bartholdi, Drahomir Aujesky, Jonas Marschall, Rami Sommerstein

2020-Current year OA Pubs

BACKGROUND: The guideline-driven and widely implemented single room isolation strategy for respiratory viral infections (RVI) such as influenza or respiratory syncytial virus (RSV) can lead to a shortage of available hospital beds. We discuss our experience with the introduction of droplet precautions on-site (DroPS) as a possible alternative.

METHODS: During the 2018/19 influenza season we introduced DroPS on several wards of a single tertiary care center, while other wards maintained the traditional single room isolation strategy. On a daily basis, we evaluated patients for the development of respiratory symptoms and screened those with a clinical diagnosis of hospital-acquired respiratory viral …

Associations Between Resources And Practices Of Ild Centers And Outcomes In Patients With Idiopathic Pulmonary Fibrosis: Data From The Ipf-Pro Registry, Joao A De Andrade, Tejaswini Kulkarni, Megan L Neely, Anne S Hellkamp, Amy Hajari Case, Daniel A Culver, Kalpalatha Guntupalli, Shaun Bender, Craig S Conoscenti, Laurie D Snyder, Ipf-Pro Registry Investigators

Faculty, Staff and Students Publications

BACKGROUND: Performance benchmarks for the management of idiopathic pulmonary fibrosis (IPF) have not been established. We used data from the IPF-PRO Registry, an observational registry of patients with IPF managed at sites across the US, to examine associations between the characteristics of the enrolling sites and patient outcomes.

METHODS: An online survey was used to collect information on the resources, operations, and self-assessment practices of IPF-PRO Registry sites that enrolled ≥ 10 patients. Site variability in 1-year event rates of clinically relevant outcomes, including death, death or lung transplant, and hospitalization, was assessed. Models were adjusted for differences in patient …