Medicine and Health Sciences Commons^™

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Faculty, Staff and Student Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Predicting Kidney Graft Function And Failure Among Kidney Transplant Recipients, Yi Yao, Brad C Astor, Wei Yang, Tom Greene, Liang Li

Faculty, Staff and Student Publications

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of …

Implications Of Myocardial Strain In Primary Mitral Regurgitation-A Cardiovascular Magnetic Resonance Study, Simone Romano, Danai Kitkungvan, Duc T Nguyen, Carlos El-Tallawi, Edward A Graviss, Afshin Farzaneh-Far, Dipan J Shah

Faculty, Staff and Student Publications

Aims: Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodelling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction (EF). Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine images. The aim of this study is to evaluate the prognostic value of CMR feature tracking-derived GLS in patients with primary MR.

Methods and results: Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patients with LVEF < 50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised (i) referral for mitral surgery owing to symptoms or LV systolic dysfunction or (ii) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, and the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). At multivariable analysis, GLS≥ -16.6% was associated with primary outcome [hazard ratio (HR) 1.90, P = 0.01]. In moderate MR cohort, patients with GLS≥ -16.6% had worse event-free survival, whereas there was no significant difference in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (HR 2.24, P = 0.02).

Conclusion: In patients with primary MR with preserved systolic function, GLS was associated with our composite …

Transcriptomic Profile Analysis Of Brain Tissue In The Absence Of Functional Trpm8 Calcium Channel, Erick B Saldes, Alexandra Erdmier, Jai Velpula, Timothy E Koeltzow, Michael X Zhu, Swapna Asuthkar

Faculty, Staff and Student Publications

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca2+-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson's disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in …

Addressing Unprofessional Behaviors In The Clinical Learning Environment: Lessons From A Multi-Year Virtual, Intergenerational, Interdisciplinary Workshop, Stacey Rose, Anita Kusnoor, Phuong Huynh, Jocelyn Greely, Yesenia Rojas-Khalil, Doris Kung, Anne Gill, Nadia Ismail, Nital Appelbaum

Faculty, Staff and Students Publications

INTRODUCTION: Optimizing the clinical learning environment (CLE) is a medical education priority nationwide.

MATERIALS AND METHODS: We developed a virtual, one-hour workshop engaging students, housestaff and faculty in small-group discussions of five case scenarios adapted from reported unprofessional behaviors in the CLE, plus didactics regarding mistreatment, microaggressions and bystander interventions.

RESULTS: Over two sessions (2021-2022), we engaged 340 students and 73 faculty/housestaff facilitators. Post-session surveys showed significant improvement in participants' ability to recognize and respond to challenges in the CLE.

DISCUSSION: Our innovative workshop, including scenarios derived from institutional reports of unprofessional behaviors, advanced participants' knowledge and commitment to improve …

Approved Car-T Therapies Have Reproducible Efficacy And Safety In Clinical Practice, Daniel Goyco Vera, Hiral Waghela, Mohamed Nuh, Jonathan Pan, Premal Lulla

Faculty, Staff and Students Publications

CAR-T cell therapy has established itself as a highly effective treatment for hematological malignancies. There are currently six commercial CAR-T products that have been FDA approved for diseases such as B-ALL, LBCL, MCL, FL, MM, and CLL/SLL. "Real-world" studies allow us to evaluate outcomes from the general population to determine their efficacy and safety compared to those who were included in the original trials. Based on several well conducted "Real-world" studies that represent diverse populations, we report that outcomes from the original trials that led to the approval of these therapies are comparable to those in practice.

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH

Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao

Faculty, Staff and Student Publications

One goal of precision medicine is to develop effective treatments for patients by tailoring to their individual demographic, clinical, and/or genetic characteristics. To achieve this goal, statistical models must be developed that can identify and evaluate potentially heterogeneous treatment effects in a robust manner. The oft-cited existing methods for assessing treatment effect heterogeneity are based upon parametric models with interactions or conditioning on covariate values, the performance of which is sensitive to the omission of important covariates and/or the choice of their values. We propose a new Bayesian nonparametric (BNP) method for estimating heterogeneous causal effects in studies with zero-inflated …

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …

Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon

Faculty, Staff and Students Publications

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related …

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …

Age-Dependent Regulation Of Axoglial Interactions And Behavior By Oligodendrocyte Ankyring, Xiaoyun Ding, Yu Wu, Anna Vainshtein, Victoria Rodriguez, Emily Ricco, James T Okoh, Yanhong Liu, Daniel C Kraushaar, Elior Peles, Matthew N Rasband

Faculty, Staff and Students Publications

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In …

Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological …

Vaccines Targeting P53 Mutants Elicit Anti-Tumor Immunity, Dafei Chai, Xu Wang, Chunmei Fan, Junhao Wang, Jing Ming Lim, Xinfang Yu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8+ T cells, NK cells, and DCs. The vaccine enhanced the induction and maturation of CD11c+, CD103+CD11c+, and CD8+CD11c+ cells, which in turn promoted tumor-specific antibody production, as well …

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …

Lack Of Association Of The Pld4 Snp Rs2841277 With Systemic Sclerosis In A European American Population, Yunqing Ma, Maureen D Mayes, Xinjian Guo, Shervin Assassi, Xiaodong Zhou

Faculty, Staff and Student Publications

This study aimed to examine whether a reported SSc-associated SNP rs2841277 in the PLD4 gene identified in an Asian population was also associated with SSc in European American (EA). The EA cohort consisting of 1005 SSc patients and 961 healthy controls was examined in this study. TaqMan genotyping assays were performed to examine the SNP. Exact P-values were obtained from 2 × 2 tables of allele counts and disease status. In contrast to the previous reports in a Japanese population, SSc patients of EA did not show an association of PLD4 rs2841277 with SSc in general (P = 0.231, OR …

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …

Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki

Faculty, Staff and Students Publications

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations. Aperiodic '1/f slope' has emerged as a promising composite measure of these brain state dynamics. However, the relationship of 1/f slope to state-dependent processes, such as saliency, is less explored, particularly intracranially in humans. Here, we record …

Development And Evaluation Of An Implementation Strategy To Increase Hpv Vaccination Among Underserved Youth Across Texas: A Protocol Paper, Paula M Cuccaro, Jihye Choi, Lara S Savas, Efrat K Gabay, Mayra Aguilar Mcbride, Amy Montelongo Eldridge, Timothy J Walker

Faculty, Staff and Student Publications

BACKGROUND: All for Them is a theory-based and evidence-informed multilevel, multicomponent program delivered through schools to increase HPV vaccination among medically underserved youth across Texas. Given the potential logistical challenges of program implementation, understanding how to best support the implementation and sustainment of the program is critical. The overall goals of this study are twofold: 1) develop a multifaceted implementation strategy, Implementing All for Them (IM-AFT); and 2) evaluate the impact of IM-AFT on implementation outcomes for schools and healthcare providers to successfully implement All for Them in their respective settings.

METHODS: This study is underpinned by a comprehensive and …

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …

Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction Via Glypican-1 Shedding, Inflammation, And Matrix Metalloproteinase 9 In Patients Undergoing Cardiac Surgery, Shiyi Li, Katherine V Nordick, Iván Murrieta-Álvarez, Randall P Kirby, Rishav Bhattacharya, Ismael Garcia, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

OBJECTIVES: A prolonged cardiopulmonary bypass (CPB) time of over 180 min is linked to poorer outcomes and higher mortality in cardiac surgery. This study examines how glypican-1 shedding, matrix metallopeptidase 9 (MMP9), and the pro-inflammatory cytokine IL-1β may contribute to endothelial dysfunction in patients undergoing on-pump surgery with an extended CPB.

METHODS: Fifty-one patients undergoing cardiac surgical procedures were divided into two groups based on the intraoperative CPB duration: (i) normal CPB (<180 >min,

RESULTS: Before surgery, the plasma levels of glypican-1, MMP9, and IL-1β were comparable between the normal CPB and the prolonged CPB groups. However, after the end …

High-Intensity Focused Ultrasound Ablation For Primary Or Salvage Prostate Cancer Therapy: Initial Outcomes In The Veteran Healthcare Setting, Sagar Patel, Ali Antar, Aly Alrabaa, Gal Saffati, Broderick Fleming, Neel Srikishen, Jeremy Slawin, Jennifer Taylor, Jeffrey Jones

Faculty, Staff and Students Publications

High-Intensity Focused Ultrasound (HIFU) provides comparable oncologic, erectile, and urinary outcomes to standard-of-care options for localized prostate cancer. This study reports the largest United States series of HIFU in veterans for both primary and salvage therapies. We retrospectively analyzed the outcomes of 43 veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center from 2018 to 2022. Primary endpoints included prostate-specific antigen (PSA) reduction and local recurrence rates. Secondary endpoints included 30-day complications, Sexual Health Inventory for Men (SHIM), and American Urological Association Symptom Score (AUASS). In our study, 31 veterans (72.1%) received primary treatment and 12 (27.9%) received …

Update On Strategies To Reduce Early Brain Injury After Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Aaron M Gusdon, Xuefang Sophie Ren, Han-Gil Jeong, Chang-Hun Lee, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Purpose of review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets.

Recent findings: Mechanism-specific translational studies are converging on several pathophysiologic pathways: improved antioxidant delivery and the Sirt1/Nrf2 pathway for reactive oxygen species; NLRP3 inflammasome and microglial polarization for inflammation; and the PI3K/Akt pathway for apoptosis. Recently identified mechanistic components, such as …

Stem Cell Activity-Coupled Suppression Of Endogenous Retrovirus Governs Adult Tissue Regeneration, Ying Lyu, Soo Jin Kim, Ericka S Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H Hassan, Miranda L Johnson, Lisa P Deliu, Yun You, Anurag Sharma, H Amalia Pasolli, Yue Lu, Jianhua Zhang, Vakul Mohanty, Ken Chen, Youn Joo Yang, Taiping Chen, Yejing Ge

Faculty, Staff and Student Publications

Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair …

Multisociety Endorsement Of The 2024 European Guideline Recommendations On Coronary Revascularization, Victor Dayan, Joseph F Sabik, Minoru Ono, Marc Ruel, Song Wan, Lars G Svensson, Leonard N Girardi, Y Joseph Woo, Vinay Badhwar, Marc R Moon, Wilson Y Szeto, Vinod H Thourani, Rui M S Almeida, Zhe Zheng, Walter J Gomes, Dawn S Hui, Rosemary F Kelly, Miguel Sousa Uva, Joanna Chikwe, Faisal G Bakaeen

Faculty, Staff and Students Publications

No abstract provided.

Impact Of American Thyroid Association's Revised Cancer Management Guidelines On Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000-2020, Pierre Fwelo, Natalia I Heredia, Ruosha Li, Ayrton Bangolo, Vignesh K Nagesh, Simcha Weissman, Xianglin L Du

Faculty, Staff and Student Publications

Background: The past four decades have seen a steady increase in thyroid cancer in the United States (US). This study investigated the impact of the American Thyroid Association (ATA)'s revised cancer management guidelines on thyroid cancer incidence trends and how the trends varied by socioeconomic, histologic, geographic, and racial and ethnic characteristics from 2000 to 2020.

Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) database to identify thyroid cancer cases diagnosed among US patients between 2000 and 2020. We employed joinpoint regression software to fit, assess, and compare thyroid cancer incidence trends over time stratified by …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …