Medical Specialties Commons^™

A Systematic Review And Meta-Analysis On Prevalence Of And Risk Factors Associated With Depression, Anxiety And Insomnia In Infectious Diseases, Including Covid-19: A Call To Action, Kai Yuan, Yong-Bo Zheng, Yi-Jie Wang, Yan-Kun Sun, Yi-Miao Gong, Yue-Tong Huang, Xuan Chen, Xiao-Xing Liu, Yi Zhong, Si-Zhen Su, Nan Gao, Yi-Long Lu, Zhe Wang, Wei-Jian Liu, Jian-Yu Que, Ying-Bo Yang, An-Yi Zhang, Meng-Ni Jing, Chen-Wei Yuan, Na Zeng, Michael V Vitiello, Vikram Patel, Seena Fazel, Harry Minas, Graham Thornicroft, Teng-Teng Fan, Xiao Lin, Wei Yan, Le Shi, Jie Shi, Thomas Kosten, Yan-Ping Bao, Lin Lu

Children’s Nutrition Research Center Staff Publications

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, …

State-Of-The-Art Review: Evidence On Red Meat Consumption And Hypertension Outcomes, Tara Shrout Allen, Harpreet S Bhatia, Alexis C Wood, Shabnam R Momin, Matthew A Allison

Children’s Nutrition Research Center Staff Publications

Hypertension (HTN) is a well-established risk factor for cardiovascular diseases (CVDs), including ischemic heart disease, stroke, heart failure, and atrial fibrillation. The prevalence of HTN, as well as mortality rates attributable to HTN, continue to increase, particularly in the United States and among Black populations. The risk of HTN involves a complex interaction of genetics and modifiable risk factors, including dietary patterns. In this regard, there is accumulating evidence that links dietary intake of red meat with a higher risk of poorly controlled blood pressure and HTN. However, research on this topic contains significant methodological limitations, which are described in …

Twist1 Interacts With Β/Δ-Catenins During Neural Tube Development And Regulates Fate Transition In Cranial Neural Crest Cells, Jessica W Bertol, Shelby Johnston, Rabia Ahmed, Victoria K Xie, Kelsea M Hubka, Lissette Cruz, Larissa Nitschke, Marta Stetsiv, Jeremy P Goering, Paul Nistor, Sally Lowell, Hanne Hoskens, Peter Claes, Seth M Weinberg, Irfan Saadi, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons and glial cells. We have previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we have investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicate that TWIST1 is expressed in endocytic vesicles at the apical surface and interacts with β/δ-catenins during neural …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations and Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

Dissertations and Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging (DWI). The …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Impact Of Somatic Mutations On Survival Outcomes In Patients With Anaplastic Thyroid Carcinoma, Jennifer Rui Wang, Matthew Montierth, Li Xu, Maitrayee Goswami, Xiao Zhao, Gilbert Cote, Wenyi Wang, Priyanka Iyer, Ramona Dadu, Naifa L Busaidy, Stephen Y Lai, Neil D Gross, Renata Ferrarotto, Charles Lu, Gary Brandon Gunn, Michelle D Williams, Mark Routbort, Mark E Zafereo, Maria E Cabanillas

Faculty, Staff and Student Publications

PURPOSE: Anaplastic thyroid carcinoma (ATC) uniformly present with aggressive disease, but the mutational landscape of tumors varies. We aimed to determine whether tumor mutations affect survival outcomes in ATC.

MATERIALS AND METHODS: Patients who underwent mutation sequencing using targeted gene panels between 2005 and 2019 at a tertiary referral center were included. Associations between mutation status and survival outcomes were assessed using Cox proportional hazards models.

RESULTS: A total of 202 patients were included, where 122 died of ATC (60%). The median follow-up was 31 months (interquartile range, 18-45 months). The most common mutations were in

CONCLUSION: Mutation analysis provides …

Mediating And Maintaining Methylation While Minimizing Mutation: Recent Advances On Mammalian Dna Methyltransferases, Xiaodong Cheng, Robert M Blumenthal

Faculty, Staff and Student Publications

Mammalian genomes are methylated on carbon-5 of many cytosines, mostly in CpG dinucleotides. Methylation patterns are maintained during mitosis via DNMT1, and regulatory factors involved in processes that include histone modifications. Methylation in a sequence longer than CpG can influence the binding of sequence-specific transcription factors, thus affecting gene expression. 5-Methylcytosine deamination results in C-to-T transition. While some mutations are beneficial, most are not; so boosting C-to-T transitions can be dangerous. Given the role of DNMT3A in establishing de novo DNA methylation during development, it is this CpG methylation and deamination that provide the major mutagenic impetus in the DNMT3A …

Assessing The Practicality Of Using A Single Knowledge-Based Planning Model For Multiple Linac Vendors, Raphael J Douglas, Adenike Olanrewaju, Lifei Zhang, Beth M Beadle, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Knowledge-based planning (KBP) has been shown to be an effective tool in quality control for intensity-modulated radiation therapy treatment planning and generating high-quality plans. Previous studies have evaluated its ability to create consistent plans across institutions and between planners within the same institution as well as its use as teaching tool for inexperienced planners. This study evaluates whether planning quality is consistent when using a KBP model to plan across different treatment machines.

Materials and methods: This study used a RapidPlan model (Varian Medical Systems) provided by the vendor, to which we added additional planning objectives, maximum dose limits, …

Love And Fear: A Special Issue, C Sue Carter, Robert Dantzer

Faculty, Staff and Student Publications

Love and fear were forged by the same fundamental evolutionary processes that permitted life on Earth. Both love and fear are deeply interwoven with the adaptive management of stress and disease. Love and fear share common roots and both can play a role in reproduction, survival, perceived safety and wellbeing. This special issue of Comprehensive Psychoneuroendocrinology focuses specifically on the causes and consequences of love from the interactive perspectives of evolution, neurobiology and culture.

Clinical Activity Of Mitogen-Activated Protein Kinase-Targeted Therapies In Patients With Non-V600 Braf-Mutant Tumors, Matthew Dankner, Yifan Wang, Rouhi Fazelzad, Benny Johnson, Caroline A Nebhan, Ibiayi Dagogo-Jack, Nathaniel J Myall, Georg Richtig, Jillian W P Bracht, Marco Gerlinger, Eiji Shinozaki, Takayuki Yoshino, Daisuke Kotani, Jason R Fangusaro, Oliver Gautschi, Julien Mazieres, Jeffrey A Sosman, Scott Kopetz, Vivek Subbiah, Michael A Davies, Anna L Groover, Ryan J Sullivan, Keith T Flaherty, Douglas B Johnson, Andrea Benedetti, David W Cescon, Anna Spreafico, George Zogopoulos, April A N Rose

Faculty, Staff and Student Publications

Purpose: Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.

Methods: We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, …

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Albiruni Abdul Razak, Neeta Somaiah, Sant Chawla, Javier Martin-Broto, Giovanni Grignani, Scott M Schuetze, Bruno Vincenzi, Andrew J Wagner, Bartosz Chmielowski, Robin L Jones, Richard F Riedel, Silvia Stacchiotti, Elizabeth T Loggers, Kristen N Ganjoo, Axel Le Cesne, Antoine Italiano, Xavier Garcia Del Muro, Melissa Burgess, Sophie Piperno-Neumann, Christopher Ryan, Mary F Mulcahy, Charles Forscher, Nicolas Penel, Scott Okuno, Anthony Elias, Lee Hartner, Tony Philip, Thierry Alcindor, Bernd Kasper, Peter Reichardt, Lore Lapeire, Jean-Yves Blay, Christine Chevreau, Claudia Maria Valverde Morales, Gary K Schwartz, James L Chen, Hari Deshpande, Elizabeth J Davis, Garth Nicholas, Stefan Gröschel, Helen Hatcher, Florence Duffaud, Antonio Casado Herráez, Roberto Diaz Beveridge, Giuseppe Badalamenti, Mikael Eriksson, Christian Meyer, Margaret Von Mehren, Brian A Van Tine, Katharina Götze, Filomena Mazzeo, Alexander Yakobson, Aviad Zick, Alexander Lee, Anna Estival Gonzalez, Andrea Napolitano, Mark A Dickson, Dayana Michel, Changting Meng, Lingling Li, Jianjun Liu, Osnat Ben-Shahar, Dane R Van Domelen, Christopher J Walker, Hua Chang, Yosef Landesman, Jatin J Shah, Sharon Shacham, Michael G Kauffman, Steven Attia

Faculty, Staff and Student Publications

Purpose: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

Methods: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Regulation And Function Of Id2 In Plasmacytoid Dendritic Cells, Rachel L Babcock, Yifan Zhou, Bhakti Patel, Taylor T Chrisikos, Laura M Kahn, Allison M Dyevoich, Yusra B Medik, Stephanie S Watowich

Faculty, Staff and Student Publications

Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-I) producing cells that promote anti-viral immune responses and contribute to autoimmunity. Development of pDCs requires the transcriptional regulator E2-2 and is opposed by inhibitor of DNA binding 2 (Id2). Prior work indicates Id2 is induced in pDCs upon maturation and may affect pDC IFN-I production via suppression of E2-2, suggesting an important yet uncharacterized role in this lineage. We found TLR7 agonists stimulate Id2 mRNA and protein expression in pDCs. We further show that transcriptional activation of Id2 is dependent on the E2 ubiquitin-conjugating enzyme Ubc13, but independent of IFN-I …

Probing The Structure And Function Of Polymerase Θ Helicase-Like Domain, Scott Vanson, Yuzhen Li, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

DNA Polymerase θ is the key actuator of the recently identified double-strand break repair pathway, theta-mediated end joining (TMEJ). It is the only known polymerase to have a 3-domain architecture containing an independently functional family A DNA polymerase tethered by a long central region to an N-terminal helicase-like domain (HLD). Full-length polymerase θ and the isolated HLD hydrolyze ATP in the presence of DNA, but no processive DNA duplex unwinding has been observed. Based on sequence and structure conservation, the HLD is classified as a member of helicase superfamily II and, more specifically, the Ski2-like family. The specific subdomain composition …

Detecting Cognitive Impairment And Dementia In The Emergency Department: A Scoping Review, Armin Nowroozpoor, Jeff Dussetschleger, William Perry, Mary Sano, Amy Aloysi, Michael Belleville, Alexandria Brackett, Jon Mark Hirshon, William Hung, Joan Michelle Moccia, Ugochi Ohuabunwa, Manish N Shah, Ula Hwang

Faculty, Staff and Student Publications

OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED).

DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners.

SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients.

METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and …

Association Of Changes In Antithrombin Activity Over Time With Responsiveness To Enoxaparin Prophylaxis And Risk Of Trauma-Related Venous Thromboembolism, Laura E Vincent, Michael M Talanker, Dakota D Butler, Xu Zhang, Jeanette M Podbielski, Yao-Wei W Wang, Amber Chen-Goodspeed, Selina L Hernandez Gonzalez, Erin E Fox, Bryan A Cotton, Charles E Wade, Jessica C Cardenas

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity < 80%).

Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis.

Design, setting, and participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January …

Predictors Of Disease Activity And Worsening In Relapsing-Remitting Multiple Sclerosis, Yinan Zhang, Stacey Cofield, Gary Cutter, Stephen Krieger, Jerry S Wolinsky, Fred Lublin

Faculty, Staff and Student Publications

Background and objectives: Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening.

Methods: The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of …

Event-Related Phase Synchronization Propagates Rapidly Across Human Ventral Visual Cortex, Oscar Woolnough, Kiefer J Forseth, Patrick S Rollo, Zachary J Roccaforte, Nitin Tandon

Faculty, Staff and Student Publications

Visual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression …

Complication Rates In Patients Using Intracavernosal Injection Therapy For Erectile Dysfunction With Or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study, Kyle A Blum, Justin P Mehr, Travis Green, Lauren Conroy, Vanessa Marino, Daniel Kim, Kailash Panchapakesan, Liam Murphy, Sravan Panuganti, Run Wang

Faculty, Staff and Student Publications

Background: Intracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI.

Aim: We sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use.

Methods: We reviewed our institutional electronic health record and identified 168 patients who were seen in …

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity In Human Sensory Neuron Somata Parallel Alterations Described In Spontaneously Active Rodent Nociceptors, Robert Y North, Max A Odem, Yan Li, Claudio Esteves Tatsui, Ryan M Cassidy, Patrick M Dougherty, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to …

3’Utr Shortening Of Has2 Promotes Hyaluronan Hyper-Synthesis And Bioenergetic Dysfunction In Pulmonary Hypertension, Victor Tseng, Scott D Collum, Ayed Allawzi, Kathryn Crotty, Samantha Yeligar, Aaron Trammell, M Ryan Smith, Bum-Yong Kang, Roy L Sutliff, Jennifer L Ingram, Soma S S K Jyothula, Rajarajan A Thandavarayan, Howard J Huang, Eva S Nozik, Eric J Wagner, C Michael Hart, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH. Herein, we identified HA synthase-2 (HAS2) in the pulmonary artery smooth muscle cell (PASMC) layer as a predominant locus of HA dysregulation. HA upregulation involves depletion of NUDT21, a master regulator of …

Covid-19: Perceived Infection Risk And Barriers To Uptake Of Pfizer-Biontech And Moderna Vaccines Among Community Healthcare Workers, Tolulope B Famuyiro, Abayomi Ogunwale, Jude Des Bordes, Mukaila Raji

Faculty, Staff and Student Publications

Background: The health and economic ramifications of the coronavirus pandemic have prompted the need for a timely and effective vaccine development. While the rollout of the COVID-19 vaccine in record time is being hailed as a scientific feat, skepticism about the safety, side effects, and even its long-term effects remain. Acceptance of the vaccine may therefore be a challenge among healthcare workers (HCWs), whose role is considered a proxy to determining the COVID-19 vaccine uptake response by the general population.

Methods: In December 2020, prior to the arrival and receipt of the Pfizer-BioNTech and Moderna COVID-19 vaccine, we conducted a …

Influenza-Induced Thrombotic Microangiopathy In A Patient With Cancer On Proteasome Inhibitor: A Diagnostic Dilemma, Christopher D Hamad, Zachary C Hoelscher, Amanda Tchakarov, Jaya Kala

Faculty, Staff and Student Publications

Thrombotic microangiopathy (TMA) in a cancer patient is a common complication of either cancer itself or anticancer therapy. Incidence of TMA from anticancer therapy was found to be > 15%, since the introduction of anti-angiogenic drugs like anti-vascular endothelial growth factor agents. It is, however, important to not ignore other causes of TMA such as bacteria, viruses, antiplatelet drugs, hereditary complement mutations, and autoimmune disorders. We present such a diagnostic dilemma in our patient who was admitted with influenza and was found to have TMA on renal biopsy, while on proteasome inhibitor (PI) therapy. With this case, we would like to …

Rationale And Design Of Savi-Aos: A Physiologic Study Of Patients With Symptomatic Moderate Aortic Valve Stenosis And Preserved Left Ventricular Ejection Fraction, Rob Eerdekens, Pim Tonino, Jo Zelis, Rik Adrichem, Jung-Min Ahn, Jesse Demandt, Ashkan Eftekhari, Mohamed El Farissi, Phillip Freeman, Abdul Rahman Ihdayhid, Nikolaos Kakouros, Dae-Hee Kim, Seung-Ah Lee, Nicolas M Van Mieghem, Waqas Qureshi, Nils P Johnson

Faculty, Staff and Student Publications

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS.

Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) …

Placental Pathology In Spontaneous And Iatrogenic Preterm Birth: Different Entities With Unique Pathologic Features, Lucy T Brink, Drucilla J Roberts, Colleen A Wright, Daan G Nel, Pawel T Schubert, Theonia K Boyd, David R Hall, Hein Odendaal

Faculty, Staff and Student Publications

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships.

METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13.

RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) …

Management Of Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumors And The Role Of Bilateral Adrenalectomy In Ectopic Cushing Syndrome, Jace P Landry, Uriel Clemente-Gutierrez, Carolina R C Pieterman, Yi-Ju Chiang, Steven G Waguespack, Camilo Jimenez, Mouhammed A Habra, Daniel M Halperin, Sarah B Fisher, Paul H Graham, Nancy D Perrier

Faculty, Staff and Student Publications

BACKGROUND: Neuroendocrine tumors can cause ectopic Cushing syndrome, and most patients have metastatic disease at diagnosis. We identified risk factors for outcome, evaluated ectopic Cushing syndrome management, and explored the role of bilateral adrenalectomy in this population.

METHODS: This was a retrospective study including patients with diagnosis of ectopic Cushing Syndrome secondary to neuroendocrine tumors with adrenocorticotropic hormone secretion treated at our quaternary referral center over a 40-year period (1980-2020).

RESULTS: Seventy-six patients were included. Mean age at diagnosis was 46.3 ± 15.8 years. Most patients (N = 61, 80%) had metastases at ectopic Cushing syndrome diagnosis. Average follow-up was …

Final Evaluation Of La Door: Proposition 47 Grant Program, Melissa M Labriola, Danielle Sobol, Stephanie Brooks Holliday, Heather Sims

Faculty, Staff and Student Publications

The Los Angeles Diversion, Outreach, and Opportunities for Recovery program (LA DOOR) was designed by the Los Angeles City Attorney's Office (LACA) to provide a comprehensive, health-focused, preventative approach that proactively engages individuals at elevated risk of returning to LACA on a new misdemeanor offense related to substance use, mental illness, or homelessness. LA DOOR was funded through the grant program of Proposition 47. Programs funded through Proposition 47 are intended to serve individuals with a history of criminal justice involvement and mental health issues or substance use disorders and to offer mental health services, substance use disorder treatment, and …

Dynamic Expression Of Schlafen 11 (Slfn11) In Circulating Tumour Cells As A Liquid Biomarker In Small Cell Lung Cancer, Bingnan Zhang, C Allison Stewart, Qi Wang, Robert J Cardnell, Pedro Rocha, Junya Fujimoto, Luisa M Solis Soto, Runsheng Wang, Veronica Novegil, Peter Ansell, Lei He, Luisa Fernandez, Adam Jendrisak, Cole Gilbertson, Joseph D Schonhoft, Jiyun Byun, Joshua Jones, Amanda K L Anderson, Ana Aparicio, Hai Tran, Marcelo V Negrao, Jianjun Zhang, Wei-Lien Wang, Ignacio I Wistuba, Jing Wang, Rick Wenstrup, Lauren A Byers, Carl M Gay

Faculty, Staff and Student Publications

Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling.

Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response.

Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine …

Ablation Of Long Noncoding Rna Malat1 Activates Antioxidant Pathway And Alleviates Sepsis In Mice, Jingshu Chen, Shu Tang, Sui Ke, James J Cai, Daniel Osorio, Andrei Golovko, Benjamin Morpurgo, Shaodong Guo, Yuxiang Sun, Melanie Winkle, George A Calin, Yanan Tian

Faculty, Staff and Student Publications

The metastasis-associated lung adenocarcinoma transcript1 (MALAT1) is a long noncoding RNA (lncRNA) and is known for its role in cancer development and prognosis. In this study, we report that MALAT1 plays an important role in regulating acute inflammatory responses in sepsis. In patient samples, MALAT1 expression was positively correlated with severity of sepsis. In cultured macrophages, LPS treatment significantly induced MALAT1 expression, while genetic ablation of MALAT1 greatly reduced proinflammatory cytokine levels. Furthermore, MALAT1-ablated mice had significantly increased survival rates in cecal ligation and puncture (CLP)-induced sepsis and LPS-induced endotoxemia. One novel and salient feature of MALAT1-ablated mice is greatly …