Medicine and Health Sciences Commons^™

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 …

Phase Ii Trial Of Atezolizumab And Bevacizumab For Treatment Of Hpv-Positive Unresectable Or Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Suyu Liu, Kangyu Lin, Haifeng Zhu, Seema Prasad, Armeen Mahvash, Priya Bhosale, Baohua Sun, Edwin R Parra, Ignacio Wistuba, Arjun Peddireddy, James Yao, Julia Mendoza-Perez, Mark Knafl, Scott E Woodman, Cathy Eng, Daniel Halperin

Faculty, Staff and Student Publications

Purpose: Anti-PD-L1 antibodies are associated with responses in < 25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Patients and methods: For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test.

Results: Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2-32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6-not …

Tumour Size Is Associated With Growth Rates Of >0.5 Cm/Year And Delayed Intervention In Small Renal Masses In Patients On Active Surveillance, Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A Fletcher, Joseph Cheaib, Khalid Alkhatib, Peter Chang, Andrew A Wagner, James M Mckiernan, Mohamad E Allaf, Phillip M Pierorazio, Nirmish Singla

Faculty, Staff and Student Publications

Objective: To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).

Materials and methods: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time-to-event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed …

Race And Clinical Outcomes In Hormone Receptor-Positive, Her2-Negative, Node-Positive Breast Cancer In The Randomized Rxponder Trial, Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky

Faculty, Staff and Student Publications

Background: The phase III RxPONDER trial has affected treatment for node-positive (1-3), hormone receptor-positive, HER2-negative breast cancer with a 21-gene recurrence score (RS) less than 26. We investigated how these findings apply to different racial and ethnic groups within the trial.

Methods: The trial randomly assigned women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS), with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathological characteristics, RS, and treatment.

Results: A total of 4048 …

Impact Of Comorbidities On The Mortality Benefits Of Lung Cancer Screening: A Post-Hoc Analysis Of The Plco And Nlst Trials, Sebastien Gendarme, Ehsan Irajizad, James P Long, Johannes F Fahrmann, Jennifer B Dennison, Seyyed Mahmood Ghasemi, Rongzhang Dou, Robert J Volk, Rafael Meza, Iakovos Toumazis, Florence Canoui-Poitrine, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Objectives: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.

Methods: We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile …

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

Faculty, Staff and Student Publications

Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Malperfusion In Patients With Acute Type A Aortic Dissection: A Nationwide Analysis, Nicholas J Goel, John J Kelly, William L Patrick, Yu Zhao, Joseph E Bavaria, Maral Ouzounian, Anthony L Estrera, Hiroo Takayama, Edward P Chen, T Brett Reece, G Chad Hughes, Eric E Roselli, Karen M Kim, Himanshu J Patel, Michael E Bowdish, Jason S Sperling, Bradley G Leshnower, Ourania Preventza, William T Brinkman, Nimesh D Desai

Faculty, Staff and Student Publications

Background: This study describes in detail the clinical burden of malperfusion associated with acute type A aortic dissection (ATAAD) in a large, national cohort and the effect of treatment strategy on outcomes.

Methods: All patients undergoing repair of ATAAD between 2017 and 2020 in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database were studied. Malperfusion was defined using STS definitions on the basis of imaging or the surgeon's evaluation. Multivariable logistic regression was used to analyze the effect of patient and treatment factors on outcomes in patients with and without malperfusion.

Results: A total of 9958 patients undergoing …

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …

Randomized Controlled Trial Of "Bounce Back Now," A Mobile App To Reduce Post-Disaster Symptoms Of Posttraumatic Stress, Depressed Mood, And Sleep Disturbance, Kenneth J Ruggiero, Arthur Andrews, Tatiana M Davidson, Yulia Gavrilova, Brian E Bunnell, Jennifer Dahne, Matthew Price, Zoe M F Brier, Gregory Cohen, Dean Kilpatrick, Ron Acierno, Sandro Galea

Faculty, Staff and Student Publications

Objective: There is tremendous public health interest in cost-efficient, scalable interventions to improve post-disaster mental health. The authors examined the efficacy of Bounce Back Now (BBN), a mobile application, versus an enhanced usual care app (EUC).

Methods: A population-based trial was conducted with a diverse sample of 1,357 adults affected by Hurricane Harvey, Irma, Maria, Florence, or Michael in 2017 and 2018. Participants were eligible if they were ≥18 years of age, had access to an Internet-accessible device, were English speaking, and lived in a hurricane-affected area. BBN is designed to address symptoms of posttraumatic stress, depression, and sleep disturbance …

Adherence To Life’S Essential 8 Is Associated With Delayed White Matter Aging, Li Feng, Zhenyao Ye, Yezhi Pan, Rozalina G Mccoy, Braxton D Mitchell, Peter Kochunov, Paul M Thompson, Jie Chen, Menglu Liang, Thu T Nguyen, Edmond Shenassa, Yan Li, Travis Canida, Hongjie Ke, Hwiyoung Lee, Song Liu, L Elliot Hong, Chixiang Chen, David K Y Lei, Shuo Chen, Tianzhou Ma

Faculty, Staff and Student Publications

Background: The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.

Methods: This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with …

Blood Pressure Misclassification Among Stroke Survivors Followed In A Comprehensive Stroke Prevention Clinic, M Carter Denny, Maha Almohamad, Emmanuel Ebirim, Adriana Morell, Munachi Okpala, Kevin O Hwang, Sean Savitz, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Hypertension is the most important modifiable risk factor for secondary stroke prevention; however, blood pressure (BP) remains uncontrolled for at least 50 % of stroke survivors following an incident stroke. Accurate in-clinic assessment of BP is important for appropriate medication titration. We evaluated misclassification of clinic BP control in a racially diverse stroke clinic population using two BP measurement methods.

Observations: We followed ischemic stroke, intracerebral hemorrhage, and transient ischemic attack patients after hospital discharge in a comprehensive stroke clinic. Casual BP was obtained using a standard office automated machine, attended by a medical assistant. BP was also measured …

Air Embolism After Percutaneous Lung Biopsy Or Ablation: A Report Of Six Cases, Rebecca Choi, Haylie Kieu-Mi Phan, Varshana Gurusamy, Rahul A Sheth, Bruno C Odisio, Kelvin Hong, Alda L Tam

Faculty, Staff and Student Publications

Systemic air embolism is a rare but potentially life-threatening complication of percutaneous lung biopsy and ablation. This report describes six patients (four male, two female) with air embolism following CT-guided lung interventions at two institutions between January 2021 and March 2024. Air embolisms were identified in locations such as the pulmonary vein, left ventricle, and coronary arteries, with clinical presentations ranging from asymptomatic to life-threatening events. Prompt intervention, including oxygen therapy, patient repositioning, and intravenous administration of epinephrine in cases of cardiac arrest, resulted in favorable outcomes. This series highlights the importance of early detection of systemic air embolism and …

Safety, Efficacy, And Adjacent-Level Fracture Risk Following Vertebral Augmentation And Radiofrequency Ablation For The Treatment Of Spine Metastases In Patients With Cancer, Jeremiah Stringam, Koustav Pal, Andrew Niekamp, Rahim Jiwani, Iwan Paolucci, Joshua D Kuban, Zeyad Metwalli, Steven Huang, Peiman Habibollahi, Stephen Chen, Steven Yevich, Milan Patel, Sumit K Subudhi, Matthew Campbell, Amol Ghia, Claudio Tatsui, Rahul A Sheth

Faculty, Staff and Student Publications

Purpose: To evaluate the safety and efficacy of vertebral augmentation (VA) and radiofrequency ablation (RFA) for treating pathologic spinal fractures in patients with cancer and adjacent fracture risk following treatment.

Materials and Methods: This single-institution retrospective study, conducted from January 2017 to September 2020, included patients with cancer who underwent percutaneous VA with or without spine RFA for pathologic spine compression fractures. The primary outcome was pain reduction, assessed using the 10-point visual analog scale before the procedure, at first follow-up, and 2–4 weeks after the procedure. Logistic regression was performed to identify factors associated with epidural cement leak.

Results: …

Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, Nicholas A Bokulich, J Gregory Caporaso, Maura L Gillison, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet

Faculty, Staff and Student Publications

Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.

Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.

Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes and measures: Oral microbiome …

Defining The Optimal Radiation-Induced Lymphopenia Metric To Discern Its Survival Impact In Esophageal Cancer, Pim J J Damen, Max Peters, Brian Hobbs, Yiqing Chen, Uwe Titt, Remi Nout, Radhe Mohan, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Purpose: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in patients with esophageal cancer has been established. However, an optimal metric for RIL remains undefined but is important for the application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Methods and materials: Patients with esophageal cancer treated with concurrent chemoradiation therapy (CRT; 2004-2022) were selected. Studied metrics included absolute lymphocyte counts (ALCs) and neutrophil counts-and calculated derivatives-at baseline and during CRT. Multivariable Cox regression models for progression-free survival (PFS) and overall survival (OS) …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

Faculty, Staff and Student Publications

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Colour Changes In The Feet: A Sign Of Autonomic Symptoms In Systemic Sclerosis, Brittany L Adler, Kamini Kuchinad, Seeun Judy Jeong, Lauren E Stiles, Ami A Shah, Tae Chung, Zsuzsanna H Mcmahan

Faculty, Staff and Student Publications

Objectives: Patients with autonomic dysfunction, or dysautonomia, often report discolouration of their dependent extremities, which is thought to be from venous pooling or acrocyanosis. A subset of patients with SSc are affected by dysautonomia but may be challenging to identify. We sought to determine whether patients with SSc who report discolouration in their feet have a higher burden of autonomic symptoms, including orthostatic, gastrointestinal (GI), urinary, secretomotor and pupillomotor.

Methods: 167 patients with SSc completed the Composite Autonomic Symptom Score (COMPASS)-31 survey, which queries whether the patient experiences discolouration of the feet or hands. We compared the COMPASS-31 subdomain scores …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

Faculty, Staff and Student Publications

Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

T2-Weighted Imaging Of Rectal Cancer Using A 3d Fast Spin Echo Sequence With And Without Deep Learning Reconstruction: A Reader Study, Dan Nguyen, Sarah Palmquist, Ken-Pin Hwang, Jingfei Ma, Usama Salem, Jia Sun, Xinzeng Wang, Jong Bum Son, Randy Ernst, Peng Wei, Harmeet Kaur, Nir Stanietzky

Faculty, Staff and Student Publications

Purpose: To compare image quality and clinical utility of a T2-weighted (T2W) 3-dimensional (3D) fast spin echo (FSE) sequence using deep learning reconstruction (DLR) versus conventional reconstruction for rectal magnetic resonance imaging (MRI).

Methods: The study included 50 patients with rectal cancer who underwent rectal MRI consecutively between July 7, 2020 and January 20, 2021 using a T2W 3D FSE sequence with DLR and conventional reconstruction. Three radiologists reviewed the two sets of images, scoring overall SNR, motion artifacts, and overall image quality on a 3-point scale and indicating clinical preference for DLR or conventional reconstruction based on those three …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Navigating Challenges In Palliative Care: A Survey On Asco Guideline Adherence Among Health Care Providers In Low- And Middle-Income Countries., Cristiane Decat Bergerot, Enrique Soto-Perez-De-Celis, Chadane Thompson, Rushil Patel, Jafar Al-Mondhiry, Tingting Zhang, Nathasha Dhawan, Darcy Burbage, Joseph Mccollom Do, Mazie Tsang, Ramy Sedhom, William E Rosa

PCI Publications and Projects

PURPOSE: Integrating palliative care into oncology is essential, yet disparities in access and quality persist, particularly in low- and middle-income countries (LMICs). The ASCO guidelines advocate for early, routine, interdisciplinary palliative care for patients with advanced cancer. Barriers to implementing these recommendations include resource limitations, inadequate training, and cultural perceptions. Recognizing these challenges is essential for improving equitable access to palliative care worldwide.

METHODS: This prospective survey assessed adherence to ASCO recommendations for palliative care integration among LMIC health care providers (HCPs). Participants were recruited via e-mail, social media, and a list of members involved in the ASCO Palliative Care …

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

Faculty, Staff and Student Publications

Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …

Azetukalner, A Novel Kv7 Potassium Channel Opener, In Adults With Major Depressive Disorder: A Randomized Clinical Trial, Noam N Butterfield, Constanza Luzon Rosenblut, Maurizio Fava, Christoph U Correll, Anthony J Rothschild, James W Murrough, Sanjay J Mathew, Gregory N Beatch, Celene Grayson, Cynthia Harden, Jenny Qian, Joe Mcintosh, Rostam Namdari, Christopher Kenney

Staff and Researcher Publications

Importance: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need.

Objective: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD.

Design, setting, and participants: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024.

Intervention: Participants were …

Antibiotic Prophylaxis With Urodynamic Studies In Spinal Cord Injury: Assessing Practice Patterns And Outcomes To Guide Future Practice In A Single Center, Du Pham, Bradley Chi, Felicia Skelton, Donna Huang

Faculty, Staff and Students Publications

Context/objective: Despite urinary tract infections (UTIs) being a common problem in patients with spinal cord injuries (SCIs), and a well-known complication of invasive urologic procedures, little consensus exists regarding the standard of care for peri-procedural antibiotic use for SCI patients undergoing urodynamics studies (UDS). Our research seeks to evaluate local antibiotic prophylaxis pattern in SCI patients undergoing UDS, assess incidence of post-procedural UTI, describe local antibiotic resistance trends, and provide antibiotic stewardship considerations to guide future practice.

Design/setting/participants: Retrospective cohort study of SCI patients undergoing UDS from January 2010 to January 2020 at a Veterans Affairs SCI Center. Data on …

Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to evaluate the validity of the Veterans Affairs Low Vision Visual Functioning Questionnaire (VALVVFQ-48) functional vision scores (FVS) in patients with USH2A-associated retinal degeneration. In addition, to correlate the change in the VALVVFQ-48 FVS with the change in visual function (VF) measurements.

Methods: The VALVVFQ-48 was administered verbally to participants ≥18 years of age at baseline, and after 2 and 4 years. Associations among changes in FVS and changes in VF measures were assessed using the Spearman correlation coefficients. Mixed effects regression models with a random intercept were used to estimate annual rates …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …