Medical Specialties Commons^™

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Evaluating Triage To Genetic Counseling Using An Online Reproductive Genetics Module, Grace Ra

Dissertations and Theses (Open Access)

The American College of Obstetricians and Gynecologists recommends genetic screening for all pregnant women. As clinical recommendations broaden and demand for prenatal screening increases, obstetric practitioners report time constraints and lack of genetics knowledge as challenges to providing sufficient pretest education. These challenges in offering routine screening are further compounded by the inequities in access to genetic counseling and testing. Thus, alternative education and service delivery models have emerged to meet the demands for prenatal genetics education and help mitigate challenges surrounding access. At UTHealth Houston, an online triage and education module, the Prenatal Genetics Education Program (PGEP), was created …

Associations Between The Timing Of 24 H Physical Activity And Diabetes Mellitus: Results From A Nationally Representative Sample Of The Us Population, Qian Xiao, Qiuyu Feng, Martin K Rutter, Gali Albalak, Heming Wang, Raymond Noordam

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 …

A Comparison Of Carbon Ions Versus Protons For Integrated Mode Ion Imaging, Mikaël Simard, Ryan Fullarton, Lennart Volz, Christoph Schuy, Daniel G Robertson, Allison Toltz, Colin Baker, Sam Beddar, Christian Graeff, Charles-Antoine Collins Fekete

Faculty, Staff and Student Publications

Background: Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single-event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is …

Advancing Understanding And Therapeutic Strategies For Nut Sarcomas: Comprehensive Review Of The Literature And Two Cases, Carlos Torrado, Elise Nassif Haddad, Neeta Somaiah, Pavlos Msaouel, Alexander J Lazar, Sarina A Piha-Paul

Faculty, Staff and Student Publications

Soft tissue sarcomas (STSs) are a group of rare cancers, among which nuclear protein in testis (NUT) sarcomas represent an ultra-rare subset driven by NUTM1 gene fusions. This article presents two unique cases of NUT sarcomas and conducts a comprehensive review of the literature to include an additional 61 cases. Our review reveals that NUT sarcoma exhibits a slightly higher incidence among women (male-to-female ratio of 1:1.03) and tends to manifest at a relatively young age (median age of 40 years). The most prevalent NUT partner genes were the MAD family in 52% of patients (33 of 63 patients, including …

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 …

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, Joletta Belton, David L H Bennett, Margarita Calvo, 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 …

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 …

Predicting Thoracic Aortic Dissection In A Diverse Biobank Using A Polygenic Risk Score, John Depaolo, Siavash Zamirpour, Sarah Abramowitz, Gina Biagetti, Renae Judy, Cameron Beeche, Jeffrey Duda, James Gee, 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 …

Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding

Faculty, Staff and Student Publications

We investigate the impact of germline variants on cancer patients' proteomes, encompassing 1,064 individuals across 10 cancer types. We introduced an approach, "precision peptidomics," mapping 337,469 coding germline variants onto peptides from patients' mass spectrometry data, revealing their potential impact on post-translational modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. We identified rare pathogenic and common germline variants in cancer genes potentially affecting proteomic features, including variants altering protein abundance and structure and variants in kinases (ERBB2 and MAP2K2) impacting phosphorylation. Precision peptidome analysis predicted destabilizing events in signal-regulatory protein alpha (SIRPA) and glial …

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 …

Genome-Wide Association Meta-Analyses Of Drug-Resistant Epilepsy, Costin Leu, Andreja Avbersek, Remi Stevelink, Helena Martins Custodio, Siwei Chen, Doug Speed, Caitlin A Bennett, Lina Jonsson, Unnur Unnsteinsdóttir, Andrea L Jorgensen, Gianpiero L Cavalleri, Norman Delanty, John J Craig, Chantal Depondt, Michael R Johnson, Bobby P C Koeleman, Emadeldin Hassanin, Maryam Erfanian Omidvar, Roland Krause, Holger Lerche, Anthony G Marson, Terence J O'Brien, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Hreinn Stefansson, Kari Stefansson, Patrick May, Benjamin M Neale, Dennis Lal, Samuel F Berkovic, Epi25 Collaborative, Epipgx Consortium, Sanjay M Sisodiya

Faculty, Staff and Student Publications

Background: Epilepsy is one of the most common neurological disorders, affecting over 50 million people worldwide. One-third of people with epilepsy do not respond to currently available anti-seizure medications, constituting one of the most important problems in epilepsy. Little is known about the molecular pathology of drug resistance in epilepsy, in particular, possible underlying genetic factors are largely unknown.

Methods: We performed a genome-wide association study (GWAS) in two epilepsy cohorts of European ancestry, comparing drug-resistant (N = 4208) to drug-responsive individuals (N = 2618) followed by meta-analyses across the studies. Next, we performed subanalyses split into two broad subtypes: …

Psychological Profiles Of Patients Reporting With Musculoskeletal Shoulder Or Elbow Pain, Chuheng Xing, Mallory B Lane, Madilyn L Feik, Jake Taylor, James M Gregory, Natalie L Myers

Faculty, Staff and Student Publications

Background: The Optimal Screening for Prediction of Referral and Outcome-Yellow Flag (OSPRO-YF) is a questionnaire that helps assess multiple psychological domains. The primary purpose of this study was to evaluate the effect of body region (shoulder and elbow) and sex on baseline OSPRO-YF scores. The secondary purpose was to evaluate the association of age on baseline OSPRO-YF scores for both shoulder and elbow patients.

Methods: 242 subjects completed 1) a demographic survey and 2) the 17-item OSPRO-YF. The OSPRO-YF estimates the individual scores of 11 psychological patient-reported outcome measures. To assess the effects of body region and sex on the …

Outcomes After Anatomic Labral Repair With All-Suture Knotless Tensionable Anchors In Primary Hip Arthroscopic Surgery: A Prospective Analysis Of 200 Consecutive Patients, David R Maldonado, Rachel E Bruning, Julio Nerys-Figueroa, Benjamin G Domb

Faculty, Staff and Student Publications

Background: Anatomic labral repair is paramount when restoring the hip suction sealing mechanism in femoroacetabular impingement syndrome (FAIS) surgery. All-suture knotless tensionable anchors have been recently proposed as an alternative; however, data are scarce.

Purpose: To report patient-reported outcome measure (PROM) scores at a minimum 2-year follow-up for patients who underwent primary hip arthroscopic surgery with labral repair using an all-suture knotless tensionable anchor with the controlled-tension anatomic technique in the setting of FAIS.

Study design: Case series; Level of evidence, 4.

Methods: Data were prospectively collected, and patients who underwent primary hip arthroscopic surgery for the treatment of FAIS …

Synchronous Clear Cell Renal Cell Carcinoma And Classic Hodgkin Lymphoma, Phuoc Christie-Nguyen, Ahmed A Ahmed, Nourhan Ibrahim, Jacob Armstrong, Brenda Mai

Faculty, Staff and Student Publications

Introduction: The coexistence of renal cell carcinoma and classic Hodgkin lymphoma is exceedingly rare, with only two documented cases. Here, we present the third case diagnosed in our institution.

Case presentation: A 46-year-old man presented with right flank pain, fever, mild pancytopenia, and renal mass on computed tomography scan, suggesting renal malignancy. Despite intravenous antibiotics and extensive workup for recurrent fever, his condition did not improve. A bone marrow biopsy revealed rare large EBV-positive B cells. Surprisingly, imaging only showed minimal intraabdominal lymphadenopathy in the perinephric region. Subsequent surgery confirmed clear cell renal cell carcinoma in the kidney and scattered …

Pathobiology Of Aortic Aneurysms And Dissections: Synthesis Of Recent Investigations And Evolving Insights, L Maximilian Buja, Bihong Zhao, Deborah Vela, Ana Segura, Navneet Narula

Faculty, Staff and Student Publications

The pathobiology of aortic disease is linked to aortic region: atherosclerosis for abdominal aorta, primary medial degeneration or aortitis for ascending thoracic aorta, and all causes for descending thoracic aorta and thoracoabdominal lesions. The pathogenesis of aortic dissection involves damage of the outer media from impaired perfusion from dysfunctional vasa vasorum, formation of discrete foci of disrupted vascular smooth muscle cell-elastic fiber extension-contractile units, and imbalance of radial sheer stress across the aortic wall, thereby creating an intimal tear and linear dissection. Thoracic aortic aneurysms develop from the chronic progression of medial degeneration coupled with the weakening of the remodeled …

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 …

Justification, Margin Values, And Analysis Populations For Oncologic Noninferiority And Equivalence Trials: A Meta-Epidemiological Study, Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.gov. Data were extracted from each trial's registration page and primary manuscript.

Results: We identified 65 noninferiority and 10 equivalence trials that collectively enrolled 61 632 patients. Of these, 61 (81%) …

Enhancing The Safety And Efficacy Of Cell Therapy With Programmed Sense-And-Respond Function, Andrew J Walters, Xiaoyu Yang, Scott D Olson, Caleb J Bashor

Faculty, Staff and Student Publications

No abstract provided.

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, …

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, Effie W Petersdorf

Faculty, Staff and Student Publications

No abstract provided.

Development Of A Treatment Decision Aid For Patients With Dysplastic Nevi Who Are Candidates For Re-Excision, Jaclyn N Roland-Mcgowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Clara Curiel-Lewandrowski, Emily Y Chu, Erin L Foster, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu

Faculty, Staff and Student Publications

No abstract provided.

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 …

Rna Sculpting By The Primordial Helix-Clasp-Helix-Strand-Loop (Hch-Sl) Motif Enforces Chemical Recognition Enabling Diverse Kh Domain Functions, John A Tainer, Susan E Tsutakawa

Faculty, Staff and Student Publications

In all domains of life, the ancient K homology (KH) domain superfamily is central to RNA processes including splicing, transcription, posttranscriptional gene regulation, signaling, and translation. Proteins with 1 to 15 KH domains bind single-strand (ss) RNA or DNA with base sequence specificity. Here, we examine over 40 KH domain experimental structures in complex with nucleic acid (NA) and define a novel Helix-clasp-Helix-Strand-Loop (HcH-SL) NA recognition motif binding 4 to 5 nucleotides using 10 to 18 residues. HcH-SL includes and extends the Gly-X-X-Gly (GXXG) signature sequence "clasp" that brings together two helices as an ∼90° helical corner. The first helix …

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 …

Treatment Of C-Met Antibody-Drug Conjugate Asymptomatic Pneumonitis With A Novel Steroid Regimen In Non-Small Cell Lung Cancer: A Case Report, Daniel A Fox, Christine Tran, Vincent Blot, David S Hong

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) are a potent class of antineoplastic drugs that deliver cytotoxic agents via targeting with monoclonal antibodies; however, ADCs are associated with high rates of lung toxicities, limiting the therapeutic potential in many patients. We report a case of a patient with metastatic non-small cell lung cancer taking the ADC telisotuzumab vedotin (Teliso V) plus osimtertinib who developed ADC-induced pneumonitis despite clinical benefit. This patient was able to tolerate treatment for a prolonged period on a novel steroid regimen, using steroids when pneumonitis was asymptomatic but radiologically evident and as a daily suppressant. This treatment strategy may have …

From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Rahat Hussain, Danielle Wu, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5

Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Siegfried K Wagner, Yujie Wang, An Ran Ran, 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 …

Comic: A Bayesian Dose Optimization Design For Drug Combination In Multiple Indications With Application To Car-T Therapies, Kai Chen, Kentaro Takeda, Ying Yuan

Faculty, Staff and Student Publications

Project Optimus, initiated by the US Food and Drug Administration (FDA), seeks to shift the focus of dose finding and selection from the maximum tolerated dose to the optimal dose that offers the most favorable risk-benefit balance. However, applying this paradigm shift to drug combination trials presents challenges, particularly due to limited sample sizes and a large two-dimensional dose exploration space. These challenges are amplified when trials involve multiple indications. To address this, we developed a two-stage Bayesian dose optimization design, called COMIC (Combination Optimization in Multiple IndiCations), to efficiently identify Optimal Biological Dose Combinations (OBDC) for multiple indications. The …

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: …