Medicine and Health Sciences Commons^™

Implementation Of Electronic Triggers To Identify Diagnostic Errors In Emergency Departments, Viralkumar Vaghani, Ashish Gupta, Usman Mir, Li Wei, Daniel R Murphy, Umair Mushtaq, Dean F Sittig, Andrew J Zimolzak, Hardeep Singh

Faculty, Staff and Students Publications

Importance: Missed diagnosis can lead to preventable patient harm.

Objective: To develop and implement a portfolio of electronic triggers (e-triggers) and examine their performance for identifying missed opportunities in diagnosis (MODs) in emergency departments (EDs).

Design, setting, and participants: In this retrospective medical record review study of ED visits at 1321 Veterans Affairs health care sites, rules-based e-triggers were developed and implemented using a national electronic health record repository. These e-triggers targeted 6 high-risk presentations for MODs in treat-and-release ED visits. A high-risk stroke e-trigger was applied to treat-and-release ED visits from January 1, 2016, to December 31, 2020. A …

Differential Gait Features Across Parkinson's Disease Clinical Subtypes, Sidney T Baudendistel, Kerri S Rawson, Christina N Lessov-Schlaggar, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Gammon M Earhart, Meghan C Campbell

2020-Current year OA Pubs

BACKGROUND: Clinical subtypes in Parkinson's disease including non-motor manifestations may be more beneficial than subtypes based upon motor manifestations alone. Inclusion of gait metrics may help identity targets for rehabilitation and potentially predict development of non-motor symptoms for individuals with Parkinson's disease. This study aims to characterize gait differences across established multi-domain subtypes.

METHODS: "Motor Only", "Psychiatric & Motor" and "Cognitive & Motor" clinical subtypes were established through motor, cognitive, and psychiatric assessment. Walking was assessed in the "OFF" medication state. Multivariate analysis of variance identified differences in gait domains across clinical subtypes.

FINDINGS: The "Motor Only" subtype exhibited the …

Benefits And Harms Of Hepatocellular Carcinoma Screening Outreach In Patients With Cirrhosis: A Multicenter Randomized Clinical Trial, Amit G Singal, Darine Daher, Manasa Narasimman, Sruthi Yekkaluri, Yan Liu, Vanessa Cerda, Chaitra Banala, Aisha Khan, Minjae Lee, Karim Seif El Dahan, Caitlin C Murphy, Jennifer R Kramer, Ruben Hernaez

Faculty, Staff and Students Publications

Background: The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis.

Methods: We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive …

Diagnoses Supported By A Computerised Diagnostic Decision Support System Versus Conventional Diagnoses In Emergency Patients (Ddx-Bro): A Multicentre, Multiple-Period, Double-Blind, Cluster-Randomised, Crossover Superiority Trial, Wolf E Hautz, Thimo Marcin, Stefanie C Hautz, Stefan K Schauber, Gert Krummrey, Martin Müller, Thomas C Sauter, Cornelia Lambrigger, David Schwappach, Mathieu Nendaz, Gregor Lindner, Simon Bosbach, Ines Griesshammer, Philipp Schönberg, Emanuel Plüss, Valerie Romann, Svenja Ravioli, Nadine Werthmüller, Fabian Kölbener, Aristomenis K Exadaktylos, Hardeep Singh, Laura Zwaan

Faculty, Staff and Students Publications

Background: Diagnostic error is a frequent and clinically relevant health-care problem. Whether computerised diagnostic decision support systems (CDDSSs) improve diagnoses is controversial, and prospective randomised trials investigating their effectiveness in routine clinical practice are scarce. We hypothesised that diagnoses made with a CDDSS in the emergency department setting would be superior to unsupported diagnoses.

Methods: This multicentre, multiple-period, double-blind, cluster-randomised, crossover superiority trial was done in four emergency departments in Switzerland. Eligible patients were adults (aged ≥18 years) presenting with abdominal pain, fever of unknown origin, syncope, or non-specific symptoms. Emergency departments were randomly assigned (1:1) to one of two …

Exome Sequencing In Asian Populations Identifies Low-Frequency And Rare Coding Variation Influencing Parkinson’S Disease Risk, Elaine Gy Chew, Zhehao Liu, Zheng Li, Sun Ju Chung, Michelle M Lian, Moses Tandiono, Yue Jing Heng, Ebonne Y Ng, Louis Cs Tan, Wee Ling Chng, Tiak Ju Tan, Esther Kl Peh, Ying Swan Ho, Xiao Yin Chen, Erin Yt Lim, Chu Hua Chang, Jonavan J Leong, Ting Xuan Peh, Ling Ling Chan, Yinxia Chao, Wing-Lok Au, Kumar M Prakash, Jia Lun Lim, Yi Wen Tay, Vincent Mok, Anne Yy Chan, Juei-Jueng Lin, Beom S Jeon, Kyuyoung Song, Clement C Tham, Chi Pui Pang, Jeeyun Ahn, Kyu Hyung Park, Janey L Wiggs, Tin Aung, Ai Huey Tan, Azlina Ahmad Annuar, Mary B Makarious, Cornelis Blauwendraat, Mike A Nalls, Laurie A Robak, Roy N Alcalay, Ziv Gan-Or, Richard Reynolds, Shen-Yang Lim, Yun Xia, Chiea Chuen Khor, Eng-King Tan, Zhenxun Wang, Jia Nee Foo

Faculty, Staff and Students Publications

Parkinson’s disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest …

Testosterone Modulation Of Muscle Transcriptomic Profile During Lifestyle Therapy In Older Men With Obesity And Hypogonadism, Viola Viola, Tagari Samanta, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Ngoc Ho Lam Nguyen, Georgia Colleluori, Yoann Barnouin, Nicola Napoli, Clifford Qualls, Benny Abraham Kaipparettu, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Testosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight-loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.

Objective: To investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high-risk older population.

Methods: Among 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently < 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26-week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.

Results: Despite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (-2% vs. -4%, respectively; p = …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …

Neuroimaging Findings In Nondemented Frail Individuals: A Systematic Review, Hamid Harandi, Soheil Mohammadi, Ali Jahanshahi, Mahsa Dolatshahi, Sogol Alikarami, Rasa Zafari, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty.

METHODS: A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two-step screening process. The studies evaluating neuroimaging findings …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Cracking The Pericellular Matrix Code: Exploring How Mmp-2, -3, And -7 Influence Matrix Breakdown And Biomechanical Properties, Benjamin Tizian Baumann, Jule Nieuwstraten, Christian Konrads, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

INTRODUCTION: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

METHODS: Human articular cartilage explants (N = 10 patients) were incubated with activated MMP-2, …

Presentation And Surgical Outcomes Of Primary Hyperparathyroidism After Radioactive Iodine Therapy, Shaleen V Sathe, Blake Sparkman, Evan Bernard, Eileen R Smith, Kevin He, Alexander Chiu, Taylor C Brown

2020-Current year OA Pubs

BACKGROUND: Radioactive iodine (RAI) is a common treatment for various thyroid diseases. Previous studies have suggested susceptibility of parathyroid glands to the mutagenic effect of RAI and the development of primary hyperparathyroidism (PHPT). We tested the possible link between prior RAI treatment, disease presentation, and treatment outcomes.

METHODS: A retrospective analysis of 704 individuals who underwent parathyroidectomy for PHPT at a tertiary care center between the years 2015 and 2023 was performed. Preoperative and postoperative parameters, including demographic characteristics, biochemical markers, imaging data, and surgical and pathology findings were collected and analyzed to compare differences in patients who had previous …

The Effects Of Burst Steroid Therapy On Short-Term Decongestion In Acute Heart Failure Patients With Pro-Inflammatory Activation: A Post Hoc Analysis Of The Cortahf Randomized, Open-Label, Pilot Trial, Jan Biegus, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The effect of steroids on congestion in patients with acute heart failure (AHF) is not known.

METHODS AND RESULTS: Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds …

Evaluating The World Health Organization's Hearts Model For Hypertension And Diabetes Management: A Pilot Implementation Study In Guatemala, Irmgardt Alicia Wellmann, Luis Fernando Ayala, Taryn M Valley, Vilma Irazola, Mark D Huffman, Michele Heisler, Peter Rohloff, Rocío Donis, Eduardo Palacios, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

METHODS: We conducted a single-arm pilot implementation trial over six months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary …

The Impact Of Quantitative Platform On Candidacy For Bronchoscopic Lung Volume Reduction: A Multi-Center Retrospective Cohort Study, Max Wayne, Suchitra Pilli, Hee Jae Choi, Nathaniel Moulton, Praveen Chenna, Allen Cole Burks, Alexander Chen

2020-Current year OA Pubs

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.

OBJECTIVES: To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.

DESIGN: A multicenter, retrospective cohort study.

METHODS: Consecutive patients referred for BLVR between January 1, 2022 and March 31, 2023 at three medical centers in the United States with the same CT scan …

Emotional Ecosystems: Understanding The Relationship Between Family Interactions And Anxiety Among Cancer Caregivers, Keisha White Makinde, Jacquelyn J Benson, Kyle A Pitzer, Maysara Mitchell, Debra Parker Oliver, George Demiris, Karla T Washington

2020-Current year OA Pubs

OBJECTIVES: Recent studies have challenged the assumption that families are invariable sources of support for cancer caregivers, noting that relationships with family members can have both positive and negative effects on caregiver well-being. This study expands upon prior literature to examine the relationship between cancer caregivers' perceptions of the quality of their family interactions and their symptoms of anxiety.

METHODS: We employed secondary analysis of baseline data from a multisite randomized clinical trial of an intervention for cancer caregivers conducted at 3 large academic palliative care clinics. We performed linear regression analyses to analyze the relationship between caregivers' perceptions of …

Examining Health Insurance And Non-Medical Challenges Among Vietnamese Americans In Texas During The Covid-19 Pandemic, Alexander Le, Saba Siddiqi, Celine Nguyen, Ben King, Paul Gerardo Yeh, Jannette Diep, Lauren Gilbert, Bich-May Nguyen

Faculty, Staff and Student Publications

When COVID-19 data on Asian Americans are available, they are frequently aggregated, concealing community-specific concerns. Consequently, there is limited COVID-19 literature on Vietnamese Americans. In this study, we investigated the association between health insurance coverage and non-medical challenges during the COVID-19 pandemic, in Vietnamese Americans in Texas. The NIH Community Engagement Alliance (CEAL) Common Survey 2 was administered electronically in English and Vietnamese and contained 23 questions about non-medical drivers of health, COVID-19 vaccination, and research participation. Vietnamese American adults in Texas were recruited between September 2021 and March 2022 via partnerships with community organizations. Responses were compared and analyzed …

Performance And Safety Of The Extravascular Implantable Cardioverter Defibrillator Through Long-Term Follow-Up: Final Results From The Pivotal Study., Paul Friedman, Francis Murgatroyd, Lucas V A Boersma, Jaimie Manlucu, Bradley P Knight, Nicolas Clémenty, Christophe Leclercq, Anish Amin, Béla Merkely, Ulrika Maria Birgersdotter-Green, Joseph Yat Sun Chan, Mauro Biffi, Reinoud Elwin Knops, Gregory Engel, Ignacio Muñoz Carvajal, Laurence M Epstein, Venkata Sagi, Jens Brock Johansen, Maciej Sterliński, Clemens Steinwender, Troy Hounshell, Richard Abben, Amy E Thompson, Yan Zhang, Christopher Wiggenhorn, Sarah Willey, Ian Crozier

Heart and Vascular Articles

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study.

METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I …

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …

Synergistic Effects Of Extra X Chromosome On Development Of Systemic Lupus Erythematosus And Sjögren Disease In Klinefelter And Triple X Syndrome: A Retrospective Cohort Study, Anna-Kay Palmer, Irene J. Tan

Einstein Health Papers

OBJECTIVE: Systemic lupus erythematosus (SLE) and Sjögren disease (SjD) are autoimmune diseases with significant female predominance. The prevalence of SLE is increased in Klinefelter syndrome (KS) compared with the general male population. Our study investigates the dose effects of extra X chromosomes on the development of SLE and SjD in KS and triple X syndrome compared with the general population.

METHODS: This multicenter, retrospective cohort study used TriNetX, a global federated research database. Using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes, patients with a diagnosis of SLE or SjD in the general population, as well as those …

Stratification System With Dual Human Endogenous Retroviruses For Predicting Immunotherapy Efficacy In Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial. ERV expression was quantified using the ERVmap algorithm …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

Federally Qualified Health Center Patients’ Experiences With Remote Patient Monitoring As Part Of Telehealth Services For Self-Measured Blood Pressure Monitoring, Natalia I Heredia, Maria E Fernandez, Ella R Garza, Jabria Pittman, Fernanda Velasco-Huerta, Tracy L Judd, Jocelyn Hunyadi, Elvis Longanga Diese, Deevakar Rogith, William B Perkison, Susan H Fenton

Faculty, Staff and Student Publications

BACKGROUND: Remote patient monitoring (RPM) for hypertension management has become increasingly popular, demonstrating benefits for both clinics and patients. However, patient engagement in self-measured blood pressure (SMBP) monitoring remains low despite healthcare providers' efforts. This study aimed to assess adherence and acceptance of RPM for SMBP among Texas Federally Qualified Health Center patients.

METHODS: Participants enrolled in the SMBP monitoring program were recruited at three health centers. Data was collected from patient health records, and a questionnaire assessed hypertension self-management, technology acceptance, intentions, and attitudes toward SMBP. Thematic analysis was conducted for open-ended responses that followed each item, and multivariate …

Federally Qualified Health Center Patients’ Experiences With Remote Patient Monitoring As Part Of Telehealth Services For Self-Measured Blood Pressure Monitoring, Natalia I Heredia, Maria E Fernandez, Ella R Garza, Jabria Pittman, Fernanda Velasco-Huerta, Tracy L Judd, Jocelyn Hunyadi, Elvis Longanga Diese, Deevakar Rogith, William B Perkison, Susan H Fenton

Faculty, Staff and Student Publications

Background: Remote patient monitoring (RPM) for hypertension management has become increasingly popular, demonstrating benefits for both clinics and patients. However, patient engagement in self-measured blood pressure (SMBP) monitoring remains low despite healthcare providers' efforts. This study aimed to assess adherence and acceptance of RPM for SMBP among Texas Federally Qualified Health Center patients.

Methods: Participants enrolled in the SMBP monitoring program were recruited at three health centers. Data was collected from patient health records, and a questionnaire assessed hypertension self-management, technology acceptance, intentions, and attitudes toward SMBP. Thematic analysis was conducted for open-ended responses that followed each item, and multivariate …

A Potential Vegf-Driven Hypothesis Of Calvarial Centripetal Proliferation In Cerebral Proliferative Angiopathy, Shigeta Miyake, Timo Krings, Tze Phei Kee, Thierry A G M Huisman

Faculty, Staff and Students Publications

Cerebral proliferative angiopathy (CPA) is a rare subtype of cerebral arteriovenous malformation, characterized by unique angiographic features and clinical presentations. Although the clinical and angiographic characteristics of CPA have been well described, their impact on the surrounding tissues remains underexplored. Herein, we investigated the presence of calvarial thickening in patients with CPA, and discuss its potential pathogenesis. This retrospective multicenter cohort study enrolled 16 CPA patients from our institutions. Patients were identified by a search of the hospital medical records for key words related to "cerebral proliferative angiopathy." Data on demographics, CPA characteristics, clinical symptoms, and calvarial thickening were collected …

Glofitamab In Relapsed/Refractory Mantle Cell Lymphoma: Results From A Phase I/Ii Study, Tycel Jovelle Phillips, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL.

METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and …

Clinical And Molecular Characteristics Of Patients With Brain Metastasis Secondary To Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Mark W Hurd, Abdelrahman Yousef, Ethan B Ludmir, Ashwathy B Pillai, Jennifer Peterson, Eugene J Koay, Sali Albarouki, Ching-Wei Tzeng, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Michael J Overman, Anirban Maitra, Shubham Pant, Brandon G Smaglo, Robert A Wolff, James Yao, John P Shen, Dan Zhao

Faculty, Staff and Student Publications

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed.

Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis …

Pooled Safety Analysis And Management Of Sotorasib-Related Adverse Events In Kras G12c-Mutated Advanced Non-Small Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Maximilian Hochmair, Ramaswamy Govindan, Mark Vincent, Anthonie J Van Der Wekken, Noemi Reguart Aransay, Kenneth J O'Byrne, Nicolas Girard, Frank Griesinger, Makoto Nishio, Simon Häfliger, Colin Lindsay, Niels Reinmuth, Astrid Paulus, Pavlos Papakotoulas, Sang-We Kim, Carlos Gil Ferreira, Giulia Pasello, Michael Duruisseaux, Spyridon Gennatas, Anastasios Dimou, Bhakti Mehta, William Kormany, Chidozie Nduka, Brooke E Sylvester, Christine Ardito-Abraham, Yang Wang, Adrianus Johannes De Langen

Faculty, Staff and Student Publications

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; …

Phase I Study Of Bms-986299, An Nlrp3 Agonist, As Monotherapy And In Combination With Nivolumab And Ipilimumab In Patients With Advanced Solid Tumors, Blessie E Nelson, Shaun O'Brien, Rahul A Sheth, David S Hong, Aung Naing, Xiaoping Zhang, Amy Xu, Lora Hamuro, Rasika Suryawanshi, Derrick Mckinley, Ruslan D Novosiadly, Sarina A Piha-Paul

Faculty, Staff and Student Publications

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials and methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Results: 36 patients were enrolled, with breast (31%), colorectal (17%), and head and neck (14%) being the more commonly enrolled cancers. Most patients (58%) had received prior immunotherapy. Therapy was well-tolerated, with G1-G2 fever (70%), neutrophilia (36%), and leukocytosis …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …