Digital Commons Network^™

Ligand-Activated Egfr/Mapk Signaling But Not Pi3k, Are Key Resistance Mechanisms To Egfr-Therapy In Colorectal Cancer, Xueping Qu, Habib Hamidi, Radia M Johnson, Ethan S Sokol, Eva Lin, Tae Won Kim, Smruthy Sivakumar, Benjamin Kaplan, Felipe De Sousa E Melo, Andrew Mancini, Matthew Wongchenko, Yi Shi, David Shames, Yibing Yan, Fortunato Ciardiello, Carlos Bais

Faculty, Staff and Student Publications

Understanding mechanisms of resistance to active therapies is crucial for developing more effective treatments. Here, we investigate resistance to anti-EGFR and anti-VEGF plus chemotherapy treatment in colorectal cancer (CRC) patients from the IMblaze370 trial (NCT02788279). While anti-VEGF does not select for secondary mutations, anti-EGFR leads to simultaneous mutations in EGFR and MAPK, but not PI3K pathway genes. Notably, we observe frequent acquired mutations in the EGFR extracellular but not intracellular domain and that patients with higher baseline expression of EGFR-ligands are prone to acquire resistant mutations. This data reveals a ligand-activated EGFR/MAPK-signaling dependency in CRC. We also observe enrichment for …

Investigating Social Network Peer Effects On Hiv Care Engagement Using A Fuzzy-Like Matching Approach: Cross-Sectional Secondary Analysis Of The N2 Cohort Study, Makella S Coudray, Britt Skaathun, Lindsay Young, Natascha Del Vecchio, Kayo Fujimoto, Justin R Knox, Mariano Kanamori, John A Schneider

Faculty, Staff and Student Publications

BACKGROUND: Social network data are essential and informative for public health research and implementation as they provide details on individuals and their social context. For example, health information and behaviors, such as HIV-related prevention and care, may disseminate within a network or across society. By harmonizing egocentric and digital networks, researchers may construct a sociocentric-like "fuzzy" network based on a subgroup of the population.

OBJECTIVE: We aimed to generate a more complete sociocentric-like "fuzzy" network by harmonizing alternative sources of egocentric and digital network data to examine relationships between participants in the Neighborhoods and Networks (N2) cohort study. Further, we …

Rationale For A 4-Month, Parallel-Group, Randomized Controlled Trial To Assess The Feasibility And Efficacy Of A Remotely Delivered Exercise Training Intervention For Hispanics/Latinos With Multiple Sclerosis (Ferla Ms), Augusto Miravalle, Robert W Motl

Faculty, Staff and Student Publications

Background: Hispanic/Latino individuals with multiple sclerosis (MS) face greater disease burden and comorbidity due to limited healthcare access, underrepresentation in research, and social determinants of health (SDOH). Exercise training could manage health outcomes, but existing intervention research lacks Hispanic/Latino representation.

Methods: We propose a feasibility and efficacy study of a theory-based, remotely delivered exercise training intervention for enhancing health outcomes in Hispanics/Latinos with MS. This study involves a randomized controlled trial (RCT) design and compares an MS-specific exercise training program with an active control condition over a 4-month period in a sample of 50 individuals who self-identified as Hispanic/Latino with …

Metabolic Reprogramming Driven By Ant2 Deficiency Augments T Cell Function And Anti-Tumor Immunity In Mice, Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Ifat Abramovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber, Michael Berger

Faculty, Staff and Student Publications

T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generate T cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding NAD+ regeneration. Interestingly, Ant2-/- naïve T cells exhibit enhanced activation, proliferation and effector functions compared to wild-type controls. Metabolic profiling reveals that these T cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Lastly, pharmacological inhibition of ANT …

Empathy And Psychological Outcomes In Informal Caregivers Of Community-Dwelling Older Adults: A Systematic Review And Meta-Analysis, Bruce Abbott

Faculty, Staff and Student Publications

Objectives: Scholars have increasingly recognized the crucial role that empathy plays as informal caregivers provide unpaid care to their older family and friends (i.e., care recipients). Yet, the existing literature exhibits substantial variability in study approaches and results, which limits the extent to which this literature can inform interventions intended to benefit informal caregivers. We sought to address this critical gap by synthesizing research that examined how caregivers' and care recipients' empathy were associated with caregivers' psychological health.

Methods: We conducted a literature search using PubMed, PsycInfo, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and Scopus databases …

Brain And Cerebrospinal Fluid 3d Center Of Mass Shift After Spaceflight, Michael A Williams, Bryn A Martin

Faculty, Staff and Student Publications

A subset of long-duration spaceflight astronauts at the International Space Station has been documented to develop spaceflight associated neuro-ocular syndrome (SANS). Researchers have sought to understand SANS by quantification of ocular and brain structural changes thought to be associated with weightlessness induced headward fluid shift. Brain tissue shift and cerebrospinal fluid (CSF) redistribution has been observed as measured by MRI on return to Earth, and not fully quantified. To improve the understanding of this phenomenon, we developed and applied automated methods to quantify 3D center of mass shift within the skull of the extra-axial cerebrospinal fluid (eaCSF) and brain after …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Keun-Wook Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

Enhanced Efficacy Of Ipilimumab Plus Nivolumab In Angiogenic Subtypes Of Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Li Xu, Salma Kotti, Wolf Herman Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

In metastatic clear-cell renal cell carcinoma (mccRCC), choosing between immuno-oncology (IO) combinations and IO plus anti-VEGF therapies is uncertain. The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5, which featured T-effector/cell-cycle signatures (p = 0.048). Complete responses were exclusively observed in cluster1/2 (p = 0.012), with longer progression-free survival (p = 0.014). Ipi/Nivo may particularly benefit angiogenic mccRCC, supporting molecular subtype-based treatment strategies.

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Discovery Of Novel, Potent, And Orally Bioavailable Smarca2 Proteolysis-Targeting Chimeras With Synergistic Antitumor Activity In Combination With Kirsten Rat Sarcoma Viral Oncogene Homologue G12c Inhibitors, Sasikumar Kotagiri, Yawen Wang, Yanyan Han, Xiaobing Liang, Nicholas Blazanin, Manu Sebastian, Yongying Jiang, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex, including SMARCA4 in nonsmall cell lung cancer with a frequency of up to 33% in advanced-stage disease, making it the most frequently mutated complex. We and others have identified SMARCA2 to be synthetic lethal to SMARCA4, indicating that SMARCA2 is a high-value therapeutic target. Here, we disclose the discovery and characterization of potent, selective, and orally bioavailable cereblon-based SMARCA2 PROTACs. Biochemically, we showed that YDR1 and YD54 are potent SMARCA2 degraders. Further, we showed the antitumor growth inhibitory activity of YDR1 and YD54 in SMARCA4 …

Human Pain Neuroscience And The Next Generation Of Pain Therapeutics, Bryan A Copits, Michele Curatolo, Patrick M Dougherty, Robert W Gereau, Wenqin Luo, Hakan Olausson, William Renthal, Clifford J Woolf, Guoyan Zhao

Faculty, Staff and Student Publications

The recent approval of suzetrigine for acute pain treatment highlights both the success of targeting peripheral sensory neurons for pain management and the potential of developing new pain therapies primarily in human-based systems. To realize this transformative potential, further research into somatosensation and pain neuroimmunology in human systems is essential.

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Graeme Segal, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

The Association Of Resistin With Metabolic Health And Obesity In A Mexican-American Population, Eleanor Davis, Susan P Fisher-Hoch, Absalon D Gutierrez

Faculty, Staff and Student Publications

Research on the relationship between resistin levels, metabolic health, and obesity has produced inconsistent findings across different ethnic groups, making it unclear whether lower resistin levels are associated with these conditions in Mexican-Americans. This cross-sectional study investigated the relationship between resistin, metabolic health, and obesity in an adult Mexican-American cohort (n = 1511) using multivariable linear regression analysis. Related adipokines (leptin and adiponectin) were measured simultaneously. Participants were categorized into four groups by metabolic health (healthy/unhealthy) and obesity (obese/non-obese) status. “Metabolically unhealthy” was defined as ≥2 cardiometabolic abnormalities. Obesity was defined as a BMI ≥ 30 kg/m2. We also …

Simplified Control Of Neuromuscular Stimulation Systems For Restoration Of Reach With Limb Stiffness As A Modifiable Degree Of Freedom

Faculty, Staff and Student Publications

Objective. Brain-controlled functional electrical stimulation (FES) of the upper limb has been used to restore arm function to paralyzed individuals in the lab. Able-bodied individuals naturally modulate limb stiffness throughout movements and in anticipation of perturbations. Our goal is to develop, via simulation, a framework for incorporating stiffness modulation into the currently-used ‘lookup-table-based’ FES control systems while addressing several practical issues: (1) optimizing stimulation across muscles with overlap in function, (2) coordinating stimulation across joints, and (3) minimizing errors due to fatigue. Our calibration process also needs to account for when current spread causes additional muscles to become activated. Approach. …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Amanda L Rodrigue, Margaret J Wright, Sarah E Medland, John Blangero, David C Glahn, Peter Kochunov, Douglas E Williamson, Asta K Håberg, Paul M Thompson, Neda Jahanshad

Faculty, Staff and Student Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Fang Zou, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang

Faculty, Staff and Student Publications

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …

Progressive Multifocal Leukoencephalopathy In Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study, Michelly Abreu, Chirag B Patel, Krina Patel, Fareed Khawaja, Sudhakar Tummala

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy. CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to …

Gdgse: An Algorithm To Evaluate Pathway Enrichment By Discretizing Gene Expression Values, Xiang Yang, Xiaosheng Wang

Faculty, Staff and Student Publications

We proposed gdGSE, a novel computational framework for gene set enrichment analysis. Unlike conventional methods that rely on continuous gene expression values, gdGSE employs discretized gene expression profiles to assess pathway activity. This approach effectively mitigates discrepancies caused by data distributions. This algorithm consists of two steps: (1) applying statistical thresholds binarizing gene expression matrix, and (2) converting the binarized gene expression matrix into a gene set enrichment matrix. Our results demonstrated that gdGSE could robustly extract biological insights from a diverse array of simulated and real bulk or single-cell gene expression datasets. Notably, gene set enrichment scores by gdGSE …

Language Mapping During Awake Brain Surgery In A Deaf Patient With A Brain Tumor: Illustrative Case, Ene Chibawanye I, Elizabeth Silva, Kyle Noll, Mariana Bradshaw, Katherine Connelly, Ravi Tummala, Frederick F Lang, Vinodh A Kumar

Faculty, Staff and Student Publications

Background: Signed language integrates complex sensorimotor processes involving visual and motor networks. The contribution of language regions such as Broca's and Wernicke's areas during signing is not well established. Here, the authors report the case of a 45-year-old right-handed male with congenital deafness, who communicates using American Sign Language (ASL) and Signed English, presenting with focal seizures. Imaging showed a diffuse infiltrative glioma in the right cerebral hemisphere.

Observations: Remarkably, preoperative functional MRI language activations were bihemispheric and overlapped for both traditional language paradigms and sign paradigms, suggesting that the same cortical regions of the brain are used for language …

Dynamic Vertebral Artery Recanalization As A Cause For Recurrent Posterior Circulation Thromboembolic Stroke: Illustrative Case, Hussein A Zeineddine, Gabriel Galan Castro, Antonio Dono, William W Wroe, Salvatore A D'Amato, Duncan Trimble, Nimer Adeeb, Andrew Barreto, Spiros L Blackburn

Faculty, Staff and Student Publications

Background: Posterior circulation strokes comprise one-fourth of ischemic strokes and can arise from many causes. One rare etiology is transient occlusion of the vertebral artery (VA) with head rotation due to an osteophyte, termed bow hunter's syndrome. The authors present the case of recurrent thromboembolic posterior strokes secondary to transient reopening of an osteophyte-occluded VA.

Observations: A 71-year-old man presented with dizziness and visual changes with a history of prior cervical fusion and myocardial ischemia, controlled with Plavix and aspirin. CT angiography of the neck revealed osteophyte occlusion of the right VA at C4, and MRI revealed a right posterior …

Prognostic Value Of Serum And Bronchoalveolar Lavage Fluid Galactomannan Levels In Invasive Aspergillosis: An 8-Year Experience At A Tertiary Cancer Center, Saliba Wehbe, Anne-Marie Chaftari, Ray Hachem, Hiba Dagher, Andrea Haddad, Ying Jiang, Peter Bakht, Jishna Shrestha, Peter Lamie, Robin Sherchan, Jennifer Makhoul, Patrick Chaftari, Issam I Raad

Faculty, Staff and Student Publications

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA.

Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and …

Examining Demographic, Geographic, And Temporal Patterns Of Melanoma Incidence In Texas From 2000 To 2018: Retrospective Study, Adewole S Adamson, Cici Bauer

Faculty, Staff and Student Publications

Background: Melanoma currently ranks as the fifth leading cancer diagnosis and is projected to become the second most common cancer in the United States by 2040. Melanoma detected at earlier stages may be treated with less-risky and less-costly therapeutic options.

Objective: This study aims to analyze temporal and spatial trends in melanoma incidence by stage at diagnosis (overall, early, and late) in Texas from 2000 to 2018, focusing on demographic and geographic variations to identify high-risk populations and regions for targeted prevention efforts.

Methods: We used melanoma incidence data from all 254 Texas counties from the Texas Cancer Registry (TCR) …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Antoine Italiano, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Genomic Characterization Of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features In Black Individuals, Katherine A Lawson-Michod, Jeffrey R Marks, Lindsay J Collin, David A Nix, Natalie R Davidson, Yao Yu, Courtney E Johnson, Lucas A Salas, Lauren C Peres, Casey S Greene, Joellen M Schildkraut, Jennifer A Doherty

Faculty, Staff and Student Publications

Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas …

Longitudinal Profiling Of Circulating Tumor Dna Reveals The Evolutionary Dynamics Of Metastatic Prostate Cancer During Serial Therapy, Yuehui Zhao, Naveen Ramesh, Ping Xu, Emi Sei, Min Hu, Patricia Troncoso, Christopher J Logothetis, Paul G Corn, Nicholas E Navin, Amado J Zurita

Faculty, Staff and Student Publications

Treatment decisions in metastatic castration-resistant prostate cancer are mostly guided by clinical variables, but efforts to molecularly monitor the disease remain hampered by challenges in acquiring tumor tissue repeatedly. In this study, we simultaneously profiled the genome copy number and exome in longitudinal plasma circulating tumor DNA (ctDNA) acquired before, during, and upon progression to serial treatments with androgen signaling inhibitors and taxane chemotherapy from 60 patients with metastatic castration-resistant prostate cancer (2-10 samples per patient). The genomic data were used to delineate the clonal substructure and evolutionary dynamics of each patient, and an evolutionary dynamic index was developed to …

Dosimetric Predictors Of Toxicity For Brainstem Metastases And Avms Treated With Stereotactic Radiosurgery: An International, Multi-Institutional Analysis, Raj Singh, Samantha Dayawansa, Duy Pham, Georgios Mantziaris, Selcuk Peker, Yavuz Samanci, Ali Haluk Duzkalir, David Mathieu, Anne-Marie Langlois, Molly L Egnot, Ronald E Warnick, Herwin Speckter, Erwin Lazo, Laura Mendez, Angel I Blanco, Mark J Amsbaugh, Collin Liu, Andrea Becerril-Gaitan, Yoshua Esquenazi, Ching-Jen Chen, Peter Zaki, Yun Liang, Rodney Wegner, Manjul Tripathi, Zhishuo Wei, Shivani A Jajoo, Ajay Niranjan, L Dade Lunsford, Joshua D Palmer, Jason P Sheehan

Faculty, Staff and Student Publications

Background: There are limited data on dosimetric predictors of radiation-induced changes (RICs) for brainstem metastases or arteriovenous malformations (AVMs) following single-fraction stereotactic radiosurgery (SRS).

Methods: We examined a multi-institutional cohort of patients with brainstem metastases or AVMs treated with SRS. We evaluated predictors of RICs graded per CTCAE(Common Terminology Criteria for Adverse Events), including D5%, D95%, D0.03 cc, and D0.5 cc (brainstem minus lesion). Univariate logistic regressions were initially performed with independent variables trending towards significance included on multivariate logistic regression.

Results: A total of 124 brainstem lesions treated with SRS were analyzed (21 AVMs and 103 metastases). The median …

An Updated Systematic Review And Consensus Definitions For Standardised Endpoints In Perioperative Medicine: Patient Comfort And Pain Relief, Frances Chung, Michael P W Grocott, Mark P Jensen, Henrik Kehlet, Andrea Kurz, Maxime Leger, Ulrica Nilsson, Phillip Peyton, Daniel I Sessler, Martin R Tramèr, Christopher L Wu, Alfred Health Patient Experience And Consumer Engagement Group

Faculty, Staff and Student Publications

Background: Improving comfort during and after surgery is a key concern for anaesthetists and other clinicians. With the inclusion of patient and public involvement, we undertook a Delphi consensus process to update previously recommended endpoints to be used in clinical trials evaluating treatments aiming to improve patient comfort after surgery.

Methods: We undertook a systematic review to identify domains and outcome measures of patient comfort used in perioperative studies. Focus groups, workshops, and a multi-round Delphi consensus process that included clinician-researchers and a patient experience and consumer group updated a recommended list of standardised endpoints focused on patient comfort. Consensus …

Survival In Patients With Rheumatoid Arthritis And Recently Diagnosed Early-Stage Colorectal, Lung, Or Prostate Cancer Receiving Tumour Necrosis Factor Inhibitors: A Retrospective Cohort Study, Suja S Rajan

Faculty, Staff and Student Publications

Background: Tumor necrosis factor (TNF) inhibitors could impair tumoural immunity in patients with rheumatoid arthritis and cancer. We aimed to investigate the association between survival and TNF inhibitor treatment during the first 3 years after a diagnosis of colorectal, lung, or prostate cancer in patients with rheumatoid arthritis.

Methods: In this cohort study, we conducted a secondary data analysis of the Surveillance, Epidemiology, and End Results Medicare-linked dataset. We included patients aged 66 years and older with rheumatoid arthritis diagnosed with colorectal, lung, or prostate cancer between Jan 1, 2008, and Dec 31, 2019, using ICD-O-3 site and histology codes. …

Identification Of Frailty Clusters Using Cross-Sectional Frailty And Frailty Trajectory: Cohort Of Heart Failure Veterans, Amir Sharafkhaneh, Christopher I Amos, Orna Intrator, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and diminished physiological reserves. Three-quarters (78%) of heart failure (HF) patients are frail. Traditional frailty indices (FIs) assess cross-sectional deficits, while frailty trajectories (FTs) measure changes over time.

OBJECTIVES: This study aims to examine the interaction between FI and FT to enhance risk stratification in hospitalized adults with HF.

METHODS: This retrospective cohort study utilized data from the Veterans Health Administration, including 143,687 veterans aged >50 admitted for HF from 2005 to 2019. FT measurements were derived from FI calculations for each of the 3 years before index hospitalization. Unsupervised clustering …

Associations Between The Timing Of 24 H Physical Activity And Diabetes Mellitus: Results From A Nationally Representative Sample Of The Us Population, Heming Wang

Faculty, Staff and Student Publications

Aims/hypothesis: Growing evidence suggests that timing may be an important aspect of physical activity that influences cardiometabolic health. However, the current literature is inconclusive regarding the time of day that physical activity offers the greatest metabolic advantages. We investigated associations between hourly physical activity levels and diabetes mellitus and glycaemic biomarkers in a cross-sectional and nationally representative sample of US adults.

Methods: We studied 7074 adults (mean age 48 years; 52% women) from the National Health and Nutrition Examination Survey (2011-2014). Physical activity was measured by actigraphy. A monitor-independent movement summary (MIMS) unit was used to derive the total activity …