Digital Commons Network^™

Isotonic Phase I Cancer Clinical Trial Design Utilizing Patient-Reported Outcomes, Nolan A Wages, Ruitao Lin

Faculty, Staff and Student Publications

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe a new isotonic patient-reported outcome (PRO-ISO) Phase I design with the flexibility of allocating patients to lower, more tolerable regimens if a large number of PRO-DLT events are seen at higher doses. We conduct simulation studies of the operating characteristics of the design and compared them to the patient-reported outcomes continual reassessment method (PRO-CRM). We illustrate that the PRO-ISO makes appropriate dose …

Wnt7a, Naomi M Calhoun, Richard R Behringer

Faculty, Staff and Student Publications

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

Bismuth-Infused Perivascular Wrap Facilitates Delivery Of Mesenchymal Stem Cells And Attenuation Of Neointimal Hyperplasia In Rat Arteriovenous Fistulas, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Gino Martin Canlas, Francisco M Heralde, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in …

Disparities In Breast Cancer Detection Modalities And Outcomes Among Geriatric Female Cancer Patients, Zhaoli Liu, Mathilda Nicot-Cartsonis, Biai D E Digbeu, Daoqi Gao, Sharon H Giordano, Yong-Fang Kuo

Faculty, Staff and Student Publications

This study examined racial and geographic disparities in breast cancer detection modalities (screening-, diagnostic-, or non-mammography) with cancer stage and mortality. A retrospective cohort study was conducted using Texas Cancer Registry-Medicare linkage data for geriatric women. Cancers detected through screening and diagnostic mammography had 43 % (95 % CI, 39 %-46 %, p < .0001) and 31 % (95 % CI, 27 %-35 %, p < .0001) lower all-cause mortality, and 49 % (95 % CI, 41 %-54 %, p < .0001) and 37 % (95 % CI, 32 %-43 %, p < .0001) lower cancer-specific mortality, respectively, compared to non-mammography-detected breast cancers. Patients from rural areas were 17 % (95 % CI, 1.06 - 1.29) more likely to be diagnosed with mid- (p = .0023) and advanced stage (p = .003) cancers compared to their urban counterparts. Racial or geographic disparities in cancer detection modalities with associated mortality no longer exist after adjusting for covariates. Healthcare professionals can leverage these findings to promote rural cancer health equity.

Organ Of Corti Macrophages: A Distinct Group Of Cochlear Macrophages With Potential Roles In Supporting Cell Degeneration And Survival, Mengxiao Ye, Celia Zhang, Dalian Ding, Guang-Di Chen, Henry J Adler, Rania Sharaf, Bo Hua Hu

Faculty, Staff and Student Publications

Macrophages are the primary immune cells in the cochlea, essential for maintaining cochlear homeostasis and orchestrating inflammatory responses to pathological events. Although these cells have been found in various parts of the cochlea, their presence in the organ of Corti, a critical structure for acoustic sensing, remains poorly understood. The present study was designed to examine macrophage responses to ototoxic drug-induced cochlear damage and age-related cochlear degeneration, with a particular focus on the pathological conditions that trigger macrophage recruitment into the organ of Corti. We used a model of ototoxicity induced by cyclodextrin, a cyclic oligosaccharide known for its ability …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Normative Laboratory Value Ranges In Pediatric Patients Who Underwent Evaluation For Mis-C, Thomas Graf, Nathan M Money, Sindhoosha Malay, Nori Minich, Risa Bochner, Bari Winik, Ron Kaplan, Jennifer Y Colgan, Erin Aldag, Ryan O' Sullivan, Guliz Erdem, Allayne Stephans

Faculty, Staff and Student Publications

Background and objectives: Diagnosis of multisystem inflammatory syndrome in children (MIS-C) is challenging due to symptom overlap with other common conditions. The primary objective of this multicenter study was to establish normative laboratory values in MIS-C patients and compare to patients evaluated for MIS-C who had other final diagnoses.

Methods: Five hospitals reviewed records of a cohort of patients 6 months to 18 years old who were evaluated for MIS-C between March 31st 2020 and February 1st 2022. Patient demographics, clinical presentation, and laboratory values were compared in patients with a final diagnosis of MIS-C versus all other conditions. Patients' …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Methods: We performed a retrospective chart review of 476 patients treated with ICIs for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to the results of BAL cell percentage, confirmed the diagnosis of ICIP or other …

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …

The Human Spinothalamic Tract: Lessons From Cordotomy, Anthony K Allam, Michael Benjamin Larkin, Ishan A Patel, Mohammed Hasen, David Mears, Patrick Dougherty, Ashwin Viswanathan

Faculty, Staff and Student Publications

The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and …

The Impact Of Insurance On Adolescent Transition To Adult Care, Diane V Murrell, Cassandra J Enzler, Lauren Bretz, Beth H Garland, Albert C Hergenroeder, Christine Markham, Constance M Wiemann

Faculty, Staff and Student Publications

Background: This study sought to examine how adolescents and young adults with special health care needs (AYA) prepare for managing medical insurance (private and public) as an adult and the role of insurance in locating an adult provider and engaging in care.

Methods: Twenty-eight AYA aged 18-24 years with renal, inflammatory bowel, or rheumatologic diseases completed individual semi-structured interviews designed to evaluate the impact of insurance (private vs. public) on their health care transition experiences. An interdisciplinary team of coders analyzed transcripts using The Framework Method.

Results: Three themes emerged: continuum of accepting health insurance responsibility; the impact of insurance …

Digital Otoscopy With Computer-Aided Composite Image Generation: Impact On The Correct Diagnosis, Confidence, And Time, Seda Camalan, Carl D Langefeld, Amy Zinnia, Brigham Mckee, Matthew L Carlson, Nicholas L Deep, Michael S Harris, Taha A Jan, Vivian F Kaul, Nathan R Lindquist, Jameson K Mattingly, Jay Shah, Kevin Y Zhan, Metin N Gurcan, Aaron C Moberly

Faculty, Staff and Student Publications

Objective: This study investigated the comparative performance of ear, nose, and throat (ENT) physicians in correctly detecting ear abnormalities when reviewing digital otoscopy imaging using 3 different visualization methods, including computer-assisted composite images called "SelectStitch," single video frame "Still" images, and video clips. The study also explored clinicians' diagnostic confidence levels and the time to make a diagnosis.

Study design: Clinician diagnostic reader study.

Setting: Online diagnostic survey of ENT physicians.

Methods: Nine ENT physicians reviewed digital otoscopy examinations from 86 ears with various diagnoses (normal, perforation, retraction, middle ear effusion, tympanosclerosis). Otoscopy examinations used artificial-intelligence (AI)-based computer-aided composite image …

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Single-Cell Multiome Characterizing Intercellular Communication And Intracellular Regulation Of Epithelium And Mesenchymal During Secondary Palate Development In Mice, Usama Hussein, Yulin Dai, Andi Liu, Toshiyuki Itai, Fangfang Yan, Lukas M Simon, Zhongming Zhao

Faculty, Staff and Student Publications

Cell-cell communication between adjacent tissues is fundamental to orchestrating organ morphogenesis. During secondary palate development, interactions between epithelial and mesenchymal cells regulate epithelial-mesenchymal signaling, thereby controlling cell proliferation, differentiation, and tissue patterning. However, the precise molecular mechanisms underlying these interactions remain largely unexplored. In this study, we employed single-cell multiome sequencing to simultaneously profile chromatin accessibility and gene expression in 35,150 individual cells isolated from the developing mouse secondary palate at embryonic days E12.5, E13.5, E14.0, and E14.5. Our analysis revealed that intercellular signaling plays a pivotal role in directing secondary palate morphogenesis, with WNT, BMP, and PDGF pathways emerging …

Clinician Attitudes Toward Palliative Care To Enhance The Quality Of Life For Patients With Sickle Cell Disease, Eberechi Nwogu-Onyemkpa, Amber B Amspoker, Nimrah Saleem, Aanand D Naik, Elizabeth Kvale, Ifeyinwa Osunkwo

Faculty, Staff and Student Publications

Objectives: Palliative care (PC) is rare for patients with sickle cell disease (SCD). This study evaluated clinician attitudes toward PC for SCD.

Methods: A cross-sectional survey was conducted between October 2022 and February 2023. Clinicians were recruited from institutions across the United States.

Results: Eighty-six participants completed the survey. Most were physicians (90%), female (72%), had >10 years of experience (63%), and lacked prior PC training (57%). Most participants agreed (83%) that patients with SCD would benefit from PC, disagreed (99%) that PC is only for dying patients, and expressed interest (91%) in learning about PC interventions. Clinicians with prior …

Overview Of The Head And Neck Tumor Segmentation For Magnetic Resonance Guided Applications (Hnts-Mrg) 2024 Challenge, Kareem A Wahid, Cem Dede, Dina M El-Habashy, Serageldin Kamel, Michael K Rooney, Yomna Khamis, Moamen R A Abdelaal, Sara Ahmed, Kelsey L Corrigan, Enoch Chang, Stephanie O Dudzinski, Travis C Salzillo, Brigid A Mcdonald, Samuel L Mulder, Lucas Mccullum, Qusai Alakayleh, Carlos Sjogreen, Renjie He, Abdallah S R Mohamed, Stephen Y Lai, John P Christodouleas, Andrew J Schaefer, Mohamed A Naser, Clifton D Fuller

Faculty, Staff and Student Publications

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT …

Head-To-Head Comparison Of Aptamer- And Antibody-Based Proteomic Platforms In Human Cerebrospinal Fluid Samples From A Real-World Memory Clinic Cohort, Raquel Puerta, Amanda Cano, Pablo García-González, Fernando García-Gutiérrez, Maria Capdevila, Itziar De Rojas, Clàudia Olivé, Josep Blázquez-Folch, Oscar Sotolongo-Grau, Andrea Miguel, Laura Montrreal, Pamela Martino-Adami, Asif Khan, Adelina Orellana, Yun Ju Sung, Ruth Frikke-Schmidt, Natalie Marchant, Jean Charles Lambert, Maitée Rosende-Roca, Montserrat Alegret, Maria Victoria Fernández, Marta Marquié, Sergi Valero, Lluís Tárraga, Carlos Cruchaga, Alfredo Ramírez, Mercè Boada, Bart Smets, Alfredo Cabrera-Socorro, Agustín Ruiz

Faculty, Staff and Student Publications

High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, …

Linking Transcriptome And Morphology In Bone Cells At Cellular Resolution With Generative Ai, Lu Lu, Noriaki Ono, Joshua D Welch

Faculty, Staff and Student Publications

Recent advancements in deep learning (DL) have revolutionized the capability of artificial intelligence (AI) by enabling the analysis of large-scale, complex datasets that are difficult for humans to interpret. However, large amounts of high-quality data are required to train such generative AI models successfully. With the rapid commercialization of single-cell sequencing and spatial transcriptomics platforms, the field is increasingly producing large-scale datasets such as histological images, single-cell molecular data, and spatial transcriptomic data. These molecular and morphological datasets parallel the multimodal text and image data used to train highly successful generative AI models for natural language processing and computer vision. …

Dynamic And Concordance-Assisted Learning For Risk Stratification With Application To Alzheimer’S Disease, Wen Li, Ruosha Li, Ziding Feng, Jing Ning

Faculty, Staff and Student Publications

Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of …

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 …

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 …

A Bayesian Pharmacokinetics Integrated Phase I-Ii Design To Optimize Dose-Schedule Regimes, Mengyi Lu, Ying Yuan, Suyu Liu

Faculty, Staff and Student Publications

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. …

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 …

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 …

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 …

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