Genetic Phenomena Commons^™

Predicting Thoracic Aortic Dissection In A Diverse Biobank Using A Polygenic Risk Score, John Depaolo, Siavash Zamirpour, Sarah Abramowitz, Gina Biagetti, Renae Judy, Jeffrey Duda, Walter R Witschey, Julio A Chirinos, Nicholas J Goel, Nimesh Desai, Wilson Y Szeto, Dongchuan Guo, Dianna M Milewicz, Michael G Levin, James P Pirruccello, Scott M Damrauer

Faculty, Staff and Student Publications

Background: Thoracic aortic dissection is a life-threatening condition that often occurs in the presence of aortic dilation. However, currently there are limited clinical risk factors beyond aortic diameter (AoD) used to determine individual-level dissection risk.

Objectives: The purpose of this study was to determine whether common variant genetics can be used to improve identification of individuals most at risk for dissection.

Methods: A genome-wide association study (GWAS)-by-subtraction was performed to characterize the diameter-independent genetics of thoracic aortic dissection by subtracting a GWAS of AoD from a GWAS of thoracic aortic aneurysm and dissection. A polygenic risk score (PRS) was calculated …

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, Xinzeng Wang, 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, Aashish Patel, 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 …

Pharmacotherapy And Non-Invasive Neuromodulation For Neuropathic Pain: A Systematic Review And Meta-Analysis, Nadia Soliman, Xavier Moisset, Michael C Ferraro, Daniel Ciampi De Andrade, Ralf Baron, David L H Bennett, Patrick Dougherty, Ian Gilron, Aki J Hietaharju, Koichi Hosomi, Peter R Kamerman, Harriet Kemp, Elena K Enax-Krumova, Ewan Mcnicol, Theodore J Price, Srinivasa N Raja, Andrew S C Rice, Blair H Smith, Fiona Talkington, Andrea Truini, Jan Vollert, Nadine Attal, Nanna B Finnerup, Simon Haroutounian

Faculty, Staff and Student Publications

Background: There remains a substantial unmet need for effective and safe treatments for neuropathic pain. The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis.

Methods: For this systematic review and meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024. We included double-blind, randomised, placebo-controlled trials that evaluated pharmacological and neuromodulation treatments administered for at least 3 …

Quantitative Ablation Confirmation Methods In Percutaneous Thermal Ablation Of Malignant Liver Tumors: Technical Insights, Clinical Evidence, And Future Outlook, Iwan Paolucci, Jessica Albuquerque Marques Silva, Yuan-Mao Lin, Alexander Shieh, Anna Maria Ierardi, Carlo Gazzera, Paolo Fonio, Reto Bale, Kristy K Brock, Marco Calandri, Bruno C Odisio

Faculty, Staff and Student Publications

Percutaneous image-guided thermal ablation is an established local curative-intent treatment technique for the treatment of primary and secondary malignant liver tumors. Whereas margin assessment after surgical resection can be accomplished with microscopic examination of the resected specimen, margin assessment after percutaneous thermal ablation relies on cross-sectional imaging. The critical measure of technical success is the minimal ablative margin (MAM), defined as the minimum distance between the tumor and the edge of the ablation zone. Traditionally, the MAM has been assessed qualitatively using anatomic landmarks, which has suboptimal accuracy and reproducibility and is prone to operator bias. Consequently, specialized software-based methods …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Santhi Swaroop Vege, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

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, Peiman Habibollahi, 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, …

A Phase 2 Study Of Decitabine With Or Without Carboplatin And Arsenic Trioxide In Patients With Mds And Aml, Patricia L Kropf, Woonbok Chung, Raji Shameem, Lianchun Xiao, Curt Balch, Jean-Pierre J Issa

Faculty, Staff and Student Publications

Although decitabine (DAC) shows activity against myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), patient responses are limited, and prognoses remain poor. Preclinical studies have indicated that arsenic trioxide (ATO) and carboplatin (Carbo) enhance DAC's epigenetic gene derepression. Consequently, we initiated a randomized phase 2 clinical trial evaluating DAC alone, or with Carbo or ATO, in patients with MDS/AML. Thirty patients were initially randomized to receive DAC alone (20 mg/m2, days 1-5), DAC plus Carbo (AUC 5, day 8), or DAC plus ATO (0.15 mg/kg, days 1-5), followed by adaptive randomization of 61 patients, based on response rates, for at …

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

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 …

Donor Age Matters For Haploidentical Hct Patients Even After Adjusting For Hla Factors: A Machine Learning Approach, Rohtesh S Mehta, Rodney Sparapani, Tao Wang, Stephen Spellman, Stephanie J Lee

Faculty, Staff and Student Publications

No abstract provided.

Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Yujie Wang, Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Alex Suh, Yih Chung Tham, Carol Y Cheung, Xiaohong Yang, Honghua Yu, Zongyuan Ge, Wei Wang, Bin Sheng, Yun Liu, Andrew G Lee, Alastair K Denniston, Peter Van Wijngaarden, Pearse A Keane, Ching-Yu Cheng, Mingguang He, Tien Yin Wong

Faculty, Staff and Student Publications

The eye provides novel insights into general health, as well as pathogenesis and development of systemic diseases. In the past decade, growing evidence has demonstrated that the eye's structure and function mirror multiple systemic health conditions, especially in cardiovascular diseases, neurodegenerative disorders, and kidney impairments. This has given rise to the field of oculomics-the application of ophthalmic biomarkers to understand mechanisms, detect and predict disease. The development of this field has been accelerated by three major advances: 1) the availability and widespread clinical adoption of high-resolution and non-invasive ophthalmic imaging ("hardware"); 2) the availability of large studies to interrogate associations …

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, Zeyad Metwalli, 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: …

Diroximel Fumarate Acts Through Nrf2 To Attenuate Methylglyoxal-Induced Nociception In Mice And Decrease Isr Activation In Drg Neurons, Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Rohita Arjarapu, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price

Faculty, Staff and Student Publications

Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker diabetic fatty rats have enhanced MGO signaling, engage ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated …

Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Darcy Ponce, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams

Faculty, Staff and Student Publications

Introduction: Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.

Methods: This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.

Results: Of 507 eligible patients with metastatic NSCLC, 85 …

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, Nancy U Lin, 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 …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Jina Park, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

Faculty, Staff and Student Publications

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

Tumoral And Circulating Genomic Landscape Inform Survival Differences In Colorectal Carcinomatosis, Michael G White, Reed I Ayabe, Mohammad A Zeineddine, Fadl A Zeineddine, Abdelrahman M G Yousef, Norman J Galbraith, Christopher Scally, Keith Fournier, Timothy E Newhook, Nancy Y You, Jason Willis, Scott Kopetz, George J Chang, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) …

A Biomarker Signature-Guided Clinical Trial Design For Precision Medicine, Yuan Li, Dejian Lai, Ruosha Li, Han Chen, Xuelin Huang

Faculty, Staff and Student Publications

Targeted cancer therapies aim to effectively treat patients with specific biomarker profiles. Nevertheless, these therapies may not always precisely hit their intended targets, leading to uncertainty about the specific subset of patients who will benefit. To address this uncertainty, the identification of sensitive patient subsets in clinical trials becomes crucial. Our proposed phase IIB/III clinical trial design seeks to pinpoint a biomarker signature with precision, ensuring the accurate identification of patients who will respond to a specific treatment. This approach allows for the selective enrollment of sensitive patients to maximize benefits for trial participants. We incorporate Bayesian methodology to facilitate …

Fecal Immunochemical Test Positivity Thresholds: An International Survey Of Population-Based Screening Programs, Graeme P Young, Sally C Benton, Robert S Bresalier, Han-Mo Chiu, Evelien Dekker, Marieke A M Frasa, Michael Hoffmeister, Susan Parry, Kevin Selby, Carlo Senore, Harminder Singh, Erin L Symonds

Faculty, Staff and Student Publications

Background: The fecal immunochemical test for hemoglobin (FIT) is now a widely used non-invasive test in population-based organized screening programs for colorectal neoplasia. The positivity thresholds of tests currently in use are based on the fecal hemoglobin concentration (f-Hb), but the rationale for the adopted thresholds are not well documented. To understand current global usage of FIT in screening programs we conducted an international survey of the brands of FIT used, the f-Hb positivity threshold applied and the rationale for the choice.

Methods: All members of the World Endoscopy Organization CRC Screening Committee were invited to complete an eight-element initial …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Alissa C Greenwald, 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 …

Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, David S Hong

Faculty, Staff and Student Publications

Introduction: Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors.

Methods: We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors …

Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Courtney Dinardo, Marina Konopleva, Andrew A Lane

Faculty, Staff and Student Publications

No abstract provided.

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 …

Neurotransmitter Power Plays: The Synaptic Communication Nexus Shaping Brain Cancer, Jayanta Mondal, Jason T Huse

Faculty, Staff and Student Publications

Gliomas and brain metastases are notorious for their dismal prognosis and low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern brain cancers. Recently, a groundbreaking paradigm shift has emerged, highlighting the crucial role of synaptic communication between neurons and brain tumor cells in reshaping neuronal signaling to favor tumor growth. This review delves into the pivotal interplay of synaptic mechanisms, focusing on excitatory glutamatergic and inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate to propagate excitatory signals, while GABAergic synapses employ gamma-aminobutyric acid (GABA) to inhibit neuronal firing. Glutamatergic signaling can be broadly classified …

Chemotherapy-Free Treatment With Radiotherapy And Immunotherapy For Locally Advanced Non-Small Cell Lung Cancer, M Zeeshan Ozair, Balazs Halmos, Angelica D'Aiello, Jaewon Yun, Andrea R Filippi, Steven H Lin, Nitin Ohri

Faculty, Staff and Student Publications

Background: Concurrent chemoradiotherapy (CRT) followed by immunotherapy is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), yet many patients are ineligible due to treatment-related toxicity or poor functional status. Chemotherapy-free approaches using radiotherapy (RT) and immunotherapy may offer a safer and equally effective alternative in select patient populations.

Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and relevant conference proceedings focusing on trials between 2000 and 2024. Studies investigating chemotherapy-free regimens combining RT and immunotherapy in LA-NSCLC were analyzed, with emphasis on clinical outcomes, biomarker use, treatment sequencing, radiation dose/fractionation, and safety.

Results: Multiple …

Bilateral Germ Cell Tumor Of The Testis: Biological And Clinical Implications For A Stem Versus Genetic Origin Of Cancers, Jamaal C Jackson, Darren Sanchez, Aron Y Joon, Marcos R Estecio, Andrew C Johns, Matthew Campbell, Louis L Pisters, Charles C Guo, Miao Zhang, Niki M Zacharias, Shi-Ming Tu

Faculty, Staff and Student Publications

Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. …

Cognitive Outcomes In Prostate Cancer Treatment: Insights From The Odenza Trial And Future Considerations, Bryan J Neth, Jeffrey S Wefel, Kevin T Nead

Faculty, Staff and Student Publications

No abstract provided.

Network-Based Clustering Unveils Interconnected Landscapes Of Genomic And Clinical Features Across Myeloid Malignancies, Fritz Bayer, Marco Roncador, Giusi Moffa, Kiyomi Morita, Koichi Takahashi, Jack Kuipers

Faculty, Staff and Student Publications

Myeloid malignancies exhibit considerable heterogeneity with overlapping clinical and genetic features among subtypes. We present a data-driven approach that integrates mutational features and clinical covariates at diagnosis within networks of their probabilistic relationships, enabling the discovery of patient subgroups. A key strength is its ability to include presumed causal directions in the edges linking clinical and mutational features, and account for them aptly in the clustering. In a cohort of 1323 patients, we identify subgroups that outperform established risk classifications in prognostic accuracy. Our approach generalises well to unseen cohorts with classification based on our subgroups similarly offering advantages in …

Use Of Natural Language Processing To Identify Patients With Inflammatory Breast Cancer Across A Health-Care System, Ramez Kouzy, Megumi Kai, Huong T Le-Petross, Sadia Saleem, Wendy A Woodward

Faculty, Staff and Student Publications

Early identification and referral of inflammatory breast cancer remains challenging within large health-care systems, limiting access to specialized care. We developed and evaluated an artificial intelligence-driven platform integrating natural language processing (NLP) with electronic health records to systematically identify potential inflammatory breast cancer patients across 5 campuses. Our platform analyzed 8 623 494 clinical notes, implementing a sequential review process: NLP screening followed by human validation and multidisciplinary confirmation. Initial NLP screening achieved 55.4% positive predictive value, improving to 78.4% with human-in-the-loop review. Notably, among 255 confirmed patients with inflammatory breast cancer, our system demonstrated 92.2% sensitivity, identifying 57 patients …

The Effects Of Prescribed Medications On Depressive Symptoms And Neurocognitive Performance In People With Hiv, Asante R Kamkwalala, Avery Matthews, Ankita Garg, Upal Roy, Qing Ma, Erin Sundermann, Patricia K Riggs, Mattia Trunfio, Jennifer Blanchard, David J Moore, Leah H Rubin, Scott L Letendre

Faculty, Staff and Student Publications

Background: Alterations in brain function and structure, such as depression and neurocognitive impairment, continue to occur in people with human immunodeficiency virus (HIV, PWH) taking suppressive antiretroviral therapy (ART). The lifespan of PWH has improved but the healthspan remains worse than people without HIV, in part because of aging-related diseases. As a result, polypharmacy is common and increases the risk of drug-drug interactions and adverse reactions.

Methods: This cross-sectional project investigated the relationship between 7 medication-related metrics (including anticholinergic burden), depressive symptoms, and neurocognitive performance in 491 PWH at a single center in the United States. All participants were taking …