Medicine and Health Sciences Commons^™

Comparison Of Patient Outcomes In Female Patients Undergoing Slap Repair Or Biceps Tenodesis For The Treatment Of Slap Lesions, Adeeb Hanna, Matthew Wallingford, William Johns, John Sonner, Emma Johnson, Sommer Hammoud, Brandon Erickson, Steven Cohen, Michael G. Ciccotti, Meghan Bishop, Meghan Bishop

Rowan-Virtua Research Day

Background: There is no consensus on whether SLAP repair (SR) or biceps tenodesis (BT) yields superior long-term outcomes in managing superior labrum anterior to posterior (SLAP) tears. No previous study has examined outcomes of these procedures in female patients.

Hypothesis/Purpose: The purpose of this study was to compare outcomes following SR and BT for SLAP tears in females. The authors hypothesized there would be no difference in outcomes between patients who underwent SR or BT.

Study Design: Retrospective Cohort (level III)

Methods: Female patients who underwent SR or BT for treatment of SLAP tears between 1/1/2014 and 9/1/2019 were retrospectively …

Amenorrhea And Stress Fractures In Female New Jersey Division Iii Collegiate Runners: An Opportunity For Increased Health Education, Emily Forester, Tara Pellegrino

Rowan-Virtua Research Day

Background: In the National Collegiate Athletic Association (NCAA), 9.1% of the injuries reported by Women’s cross country athletes between 2014-2019 were fractures. Although excessive exercise is a major contributor to the development of amenorrhea, there are currently no studies on the association between amenorrhea and stress fractures in NJ NCAA Division III Women’s cross country or track athletes. This study aims to determine if there is an association between incidence of amenorrhea and subsequent occurrence of stress fractures among this population.

Methods: This is a survey based study. Participants must be female athletes over the age of 18 who currently …

Srsf1 Haploinsufficiency Is Responsible For A Syndromic Developmental Disorder Associated With Intellectual Disability, Elke Bogaert, Aurore Garde, Thierry Gautier, Kathleen Rooney, Yannis Duffourd, Pontus Leblanc, Emma Van Reempts, Frederic Tran Mau-Them, Ingrid M Wentzensen, Kit Sing Au, Kate Richardson, Hope Northrup, Vincent Gatinois, David Geneviève, Raymond J Louie, Michael J Lyons, Lone Walentin Laulund, Charlotte Brasch-Andersen, Trine Maxel Juul, Fatima El It, Nathalie Marle, Patrick Callier, Raissa Relator, Sadegheh Haghshenas, Haley Mcconkey, Jennifer Kerkhof, Claudia Cesario, Antonio Novelli, Nicola Brunetti-Pierri, Michele Pinelli, Perrine Pennamen, Sophie Naudion, Marine Legendre, Cécile Courdier, Aurelien Trimouille, Martine Doco Fenzy, Lynn Pais, Alison Yeung, Kimberly Nugent, Elizabeth R Roeder, Tadahiro Mitani, Jennifer E Posey, Daniel Calame, Hagith Yonath, Jill A Rosenfeld, Luciana Musante, Flavio Faletra, Francesca Montanari, Giovanna Sartor, Alessandra Vancini, Marco Seri, Claude Besmond, Karine Poirier, Laurence Hubert, Dimitri Hemelsoet, Arnold Munnich, James R Lupski, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, Bekim Sadikovic, Jérôme Govin, Bart Dermaut, Antonio Vitobello

Faculty, Staff and Students Publications

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals …

Associations Between Cannabis Use, Polygenic Liability For Schizophrenia, And Cannabis-Related Experiences In A Sample Of Cannabis Users, Emma C Johnson, Sarah M C Colbert, Paul W Jeffries, Rebecca Tillman, Nicole R Karcher, Elliot C Nelson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

BACKGROUND AND HYPOTHESIS: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs.

STUDY DESIGN: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African …

Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca²⁺ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca²⁺] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca²⁺ accumulation, thereby reducing ROS production and stress-induced intracellular Ca²⁺ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca²⁺] in female rat VCMs challenged …

Association Of Prenatal Depression With New Cardiovascular Disease Within 24 Months Postpartum., Christina M Ackerman-Banks, Heather S Lipkind, Kristin Palmsten, Mariah Pfeiffer Rn, Mph, Catherine Gelsinger Rn, Katherine Ahrens Mph, Phd

Population Health

No abstract provided.

3-Year Outcomes After Transcatheter Or Surgical Aortic Valve Replacement In Low-Risk Patients With Aortic Stenosis., John K Forrest, G Michael Deeb, Steven J Yakubov, Hemal Gada, Mubashir A Mumtaz, Basel Ramlawi, Tanvir Bajwa, Paul S Teirstein, Michael Defrain, Murali Muppala, Bruce J Rutkin, Atul Chawla, Bart Jenson, Stanley J Chetcuti, Robert C Stoler, Marie-France Poulin, Kamal Khabbaz, Melissa Levack, Kashish Goel, Didier Tchétché, Ka Yan Lam, Pim A L Tonino, Saki Ito, Jae K Oh, Jian Huang, Jeffrey J Popma, Neal Kleiman, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: Randomized data comparing outcomes of transcatheter aortic valve replacement (TAVR) with surgery in low-surgical risk patients at time points beyond 2 years is limited. This presents an unknown for physicians striving to educate patients as part of a shared decision-making process.

OBJECTIVES: The authors evaluated 3-year clinical and echocardiographic outcomes from the Evolut Low Risk trial.

METHODS: Low-risk patients were randomized to TAVR with a self-expanding, supra-annular valve or surgery. The primary endpoint of all-cause mortality or disabling stroke and several secondary endpoints were assessed at 3 years.

RESULTS: There were 1,414 attempted implantations (730 TAVR; 684 surgery). Patients …

State-Level Macro-Economic Factors Moderate The Association Of Low Income With Brain Structure And Mental Health In U.S. Children, David G Weissman, Mark L Hatzenbuehler, Mina Cikara, Deanna M Barch, Katie A Mclaughlin

2020-Current year OA Pubs

Macrostructural characteristics, such as cost of living and state-level anti-poverty programs relate to the magnitude of socioeconomic disparities in brain development and mental health. In this study we leveraged data from the Adolescent Brain and Cognitive Development (ABCD) study from 10,633 9-11 year old youth (5115 female) across 17 states. Lower income was associated with smaller hippocampal volume and higher internalizing psychopathology. These associations were stronger in states with higher cost of living. However, in high cost of living states that provide more generous cash benefits for low-income families, socioeconomic disparities in hippocampal volume were reduced by 34%, such that …

Spatial Transcriptomics Depict Ligand-Receptor Cross-Talk Heterogeneity At The Tumor-Stroma Interface In Long-Term Ovarian Cancer Survivors, Sammy Ferri-Borgogno, Ying Zhu, Jianting Sheng, Jared K Burks, Javier A Gomez, Kwong Kwok Wong, Stephen T C Wong, Samuel C Mok

Faculty, Staff and Student Publications

Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. To investigate the stromal heterogeneity of the tumor microenvironment (TME) in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment-naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Outcomes Of The "Brca Quality Improvement Dissemination Program": An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems., Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Oncology Articles

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …

The Impact Of Maternal Diabetes On Birth To Placental Weight Ratio And Umbilical Cord Oxygen Values With Implications For Fetal-Placental Development, Sheryl Choo, Barbra De Vrijer, Timothy R H Regnault, Hilary K Brown, Larry Stitt, Bryan S Richardson

Obstetrics & Gynaecology Publications

Introduction

We determined the impact of gestational diabetes (GDM) and pre-existing diabetes (DM) on birth/placental weight and cord oxygen values with implications for placental efficiency and fetal-placental growth and development.

Methods

A hospital database was used to obtain birth/placental weight, cord PO₂ and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA >34 weeks (N = 69,854). Oxygen saturation was calculated from the cord PO₂ and pH data, while fetal O₂ extraction was calculated from the oxygen saturation data. The effect of diabetic status on birth/placental weight and cord oxygen values …

Assessing Gaps In Motherhood After Cancer: Development And Psychometric Testing Of The Survivorship Oncofertility Barriers Scale, Aubri Hoffman, Chloe Josephine Denham, Shuangshuang Fu, Tito Mendoza, Roni Nitecki, Kirsten A Jorgensen, Jose Garcia, Kelly Lamiman, Terri L Woodard, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: With a growing population of young cancer survivors, there is an increasing need to address the gaps in evidence regarding cancer survivors' obstetric outcomes, fertility care access, and experiences. As part of a large research program, this study engaged survivors and experts in co-developing and testing the validity, reliability, acceptability, and feasibility of a scale to assess survivor-reported barriers to motherhood after cancer.

Methods: Scale items were developed based on literature and expert review of 226 reproductive health items, and six experience and focus groups with 26 survivors of breast and gynecological cancers. We then invited 128 survivors to …

Food Insecurity, Snap Participation And Glycemic Control In Low-Income Adults With Predominantly Type 2 Diabetes: A Cross-Sectional Analysis Using Nhanes 2007-2018 Data, Oluwatobi Alawode, Sarah Humble, Cynthia J Herrick

2020-Current year OA Pubs

INTRODUCTION: Diabetes, characterized by elevated blood glucose levels, affects 13% of US adults, 95% of whom have type 2 diabetes (T2D). Social determinants of health (SDoH), such as food insecurity, are integral to glycemic control. The Supplemental Nutrition Assistance Program (SNAP) aims to reduce food insecurity, but it is not clear how this affects glycemic control in T2D. This study investigated the associations between food insecurity and other SDoH and glycemic control and the role of SNAP participation in a national socioeconomically disadvantaged sample.

RESEARCH DESIGN AND METHODS: Adults with likely T2D and income

RESULTS: The study population included 2084 …

Association Of Sex With Neurobehavioral Markers Of Executive Function In 2-Year-Olds At High And Low Likelihood Of Autism, Tanya St John, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored.

OBJECTIVE: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL …

Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa

2020-Current year OA Pubs

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year.

OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery.

STUDY DESIGN: The Medicare 5% Limited Data Set was queried from …

Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Nandini Raghuraman, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.

OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …

Examining Mental Health, Education, Employment, And Pain In Sickle Cell Disease, Kelly M Harris, Liliana Preiss, Taniya Varughese, Anna Bauer, Cecelia L Calhoun, Marsha Treadwell, Rita Masese, Jane S Hankins, Faiz Ahmed Hussain, Jeffrey Glassberg, Cathy L Melvin, Robert Gibson, Allison A King, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

IMPORTANCE: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain.

OBJECTIVE: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD.

DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022.

MAIN …

Neighborhood Deprivation And Association With Neonatal Intensive Care Unit Mortality And Morbidity For Extremely Premature Infants, Brynne A Sullivan, Ayush Doshi, Pavel Chernyavskiy, Ameena Husain, Alexandra Binai, Rakesh Sahni, Karen D Fairchild, J Randall Moorman, Colm P Travers, Zachary A Vesoulis

2020-Current year OA Pubs

IMPORTANCE: Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.

OBJECTIVE: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 …

Patterns In Use And Transplant Outcomes Among Adult Recipients Of Kidneys From Deceased Donors With Covid-19, Mengmeng Ji, Amanda J Vinson, Su-Hsin Chang, Massini Merzkani, Krista L Lentine, Yasar Caliskan, Kristin Progar, Nicole Nesselhauf, Casey Dubrawka, Tarek Alhamad

2020-Current year OA Pubs

IMPORTANCE: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown.

OBJECTIVE: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs …

Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint

2020-Current year OA Pubs

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …

A Randomized, Open-Label Study Of The Tolerability And Efficacy Of One Or Three Daily Doses Of Ivermectin Plus Diethylcarbamazine And Albendazole (Ida) Versus One Dose Of Ivermectin Plus Albendazole (Ia) For Treatment Of Onchocerciasis, Nicholas O. Opoku, Nicole Fetcho, Kerstin Fischer, Peter U. Fischer, Charles W. Goss, Augustine R. Hong, Daphne Lew, Gary J. Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis.

METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with …

Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.

2020-Current year OA Pubs

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …

Influence Of Genomic Landscape On Cancer Immunotherapy For Newly Diagnosed Ovarian Cancer: Biomarker Analyses From The Imagyn050 Randomized Clinical Trial, Charles N Landen, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.

PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations …

Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.

EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome …

Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

PURPOSE: Economic empowerment and family strengthening interventions have shown promise for improving psychosocial well-being in a range of populations. This study investigates the effect of a combination economic and family strengthening intervention on psychosocial well-being among Ugandan adolescent girls and young women (AGYW).

METHODS: We harnessed data from a three-arm cluster randomized controlled trial among AGYW aged 14-17 years in 47 Ugandan secondary schools. Schools were randomized to either a youth development account intervention (YDA) [N = 16 schools], YDA plus a multiple family group intervention (YDA + MFG) [N = 15 schools], or bolstered standard of care (BSOC) [N …

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …

Efficacy Of Alternative Dose Regimens Of Exemestane In Postmenopausal Women With Stage 0 To Ii Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial, Davide Serrano, Sara Gandini, Parjhitham Thomas, Katherine D Crew, Nagi B Kumar, Lana A Vornik, J Jack Lee, Paolo Veronesi, Giuseppe Viale, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Harriet Johansson, Mauro D'Amico, Flavio Guasone, Stefano Spinaci, Bjørn-Erik Bertelsen, Gunnar Mellgren, Isabelle Bedrosian, Diane Weber, Tawana Castile, Eileen Dimond, Brandy M Heckman-Stoddard, Eva Szabo, Powel H Brown, Andrea Decensi, Bernardo Bonanni

Faculty, Staff and Student Publications

IMPORTANCE: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events.

OBJECTIVE: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer …

Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Amir A Shamshirsaz, Alison G Cahill, Mark A Turrentine, Angela R Seasely, Joe Eid, Caroline E Rouse, Michael Richley, Nandini Raghuraman, Mariam Naqvi, Yasser Y El-Sayed, Martina L Badell, Cece Cheng, James Liu, Emily H Adhikari, Soha S Patel, Erika R O'Neil, Patrick S Ramsey

Faculty, Staff and Student Publications

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.

OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …

Outcomes Of The “Brca Quality Improvement Dissemination Program”: An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems, Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …