Digital Commons Network^™

Langerhans Cell Histiocytosis In Children Born After Assisted Reproductive Technology, Carrie L Williams, Kathryn J Bunch, Charles Stiller, Michael F G Murphy, Beverley J Botting, Melanie C Davies, Barbara Luke, Philip J Lupo, Alastair G Sutcliffe

Center for Medical Ethics and Health Policy Staff Publications

Research question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?

Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence …

A Proteome-Wide Association Study Identifies Putative Causal Proteins For Breast Cancer Risk, Tianying Zhao, Shuai Xu, Jie Ping, Guochong Jia, Yongchao Dou, Jill E Henry, Bing Zhang, Xingyi Guo, Michele L Cote, Qiuyin Cai, Xiao-Ou Shu, Wei Zheng, Jirong Long

Faculty, Staff and Students Publications

BACKGROUND: Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk.

METHODS: We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …

Effects Of Trauma Exposure And Posttraumatic Stress Disorder On Perceived Social Support In Youth: A Longitudinal Investigation, Erin Logue, John Leri, Jeffrey D Shahidullah, Caitlin M Pinciotti, Paul J Rathouz, Josh M Cisler, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff

Faculty, Staff and Students Publications

The aim of this study was to examine relationships among trauma burden, post-traumatic stress disorder, and perceived social support in a large, diverse group of trauma-exposed children and adolescents followed longitudinally. Specifically, we tested the social erosion hypothesis (i.e., mental health challenges negatively affect the quality of social relationships and contribute to reduced social support over time) using a sample of 1,829 trauma-exposed youth (aged 8-21) recruited through the multi-site Texas Childhood Trauma Research Network. Youth who reported more trauma burden (i.e., a greater number of traumas) perceived significantly lower levels of social support from family and peers, and those …

Global And Risk-Group Stratified Well-Being And Mental Health During The Covid-19 Pandemic In Adults: Results From The International Coh-Fit Study, Marco Solmi, Trevor Thompson, Andrés Estradé, Agorastos Agorastos, Joaquim Radua, Samuele Cortese, Elena Dragioti, Davy Vancampfort, Lau Caspar Thygesen, Harald Aschauer, Monika Schlögelhofer, Elena Aschauer, Andres Schneeberger, Christian G Huber, Gregor Hasler, Philippe Conus, Kim Q Do Cuénod, Roland Von Känel, Gonzalo Arrondo, Paolo Fusar-Poli, Philip Gorwood, Pierre-Michel Llorca, Marie-Odile Krebs, Elisabetta Scanferla, Taishiro Kishimoto, Golam Rabbani, Karolina Skonieczna-Żydecka, Paolo Brambilla, Angela Favaro, Akihiro Takamiya, Leonardo Zoccante, Marco Colizzi, Julie Bourgin, Karol Kamiński, Maryam Moghadasin, Soraya Seedat, Evan Matthews, John Wells, Emilia Vassilopoulou, Ary Gadelha, Kuan-Pin Su, Jun Soo Kwon, Minah Kim, Tae Young Lee, Oleg Papsuev, Denisa Manková, Andrea Boscutti, Cristiano Gerunda, Diego Saccon, Elena Righi, Francesco Monaco, Giovanni Croatto, Guido Cereda, Jacopo Demurtas, Natascia Brondino, Nicola Veronese, Paolo Enrico, Pierluigi Politi, Valentina Ciappolino, Andrea Pfennig, Andreas Bechdolf, Andreas Meyer-Lindenberg, Kai G Kahl, Katharina Domschke, Michael Bauer, Nikolaos Koutsouleris, Sibylle Winter, Stefan Borgwardt, Istvan Bitter, Judit Balazs, Pál Czobor, Zsolt Unoka, Dimitris Mavridis, Konstantinos Tsamakis, Vasilios P Bozikas, Chavit Tunvirachaisakul, Michael Maes, Teerayuth Rungnirundorn, Thitiporn Supasitthumrong, Ariful Haque, Andre R Brunoni, Carlos Gustavo Costardi, Felipe Barreto Schuch, Guilherme Polanczyk, Jhoanne Merlyn Luiz, Lais Fonseca, Luana V Aparicio, Samira S Valvassori, Merete Nordentoft, Per Vendsborg, Sofie Have Hoffmann, Jihed Sehli, Norman Sartorius, Sabina Heuss, Daniel Guinart, Jane Hamilton, John Kane, Jose Rubio, Michael Sand, Ai Koyanagi, Aleix Solanes, Alvaro Andreu-Bernabeu, Antonia San José Cáceres, Celso Arango, Covadonga M Díaz-Caneja, Diego Hidalgo-Mazzei, Eduard Vieta, Javier Gonzalez-Peñas, Lydia Fortea, Mara Parellada, Miquel A Fullana, Norma Verdolini, Eva Andrlíková, Karolina Janků, Mark J Millan, Mihaela Honciuc, Anna Moniuszko-Malinowska, Igor Łoniewski, Jerzy Samochowiec, Łukasz Kiszkiel, Maria Marlicz, Paweł Sowa, Wojciech Marlicz, Georgina Spies, Brendon Stubbs, Joseph Firth, Sarah Sullivan, Asli Enez Darcin, Hatice Aksu, Nesrin Dilbaz, Onur Noyan, Momoko Kitazawa, Shunya Kurokawa, Yuki Tazawa, Alejandro Anselmi, Cecilia Cracco, Ana Inés Machado, Natalia Estrade, Diego De Leo, Jackie Curtis, Michael Berk, Andre F Carvalho, Philip Ward, Scott Teasdale, Simon Rosenbaum, Wolfgang Marx, Adrian Vasile Horodnic, Liviu Oprea, Ovidiu Alexinschi, Petru Ifteni, Serban Turliuc, Tudor Ciuhodaru, Alexandra Bolos, Valentin Matei, Dorien H Nieman, Iris Sommer, Jim Van Os, Therese Van Amelsvoort, Ching-Fang Sun, Ta-Wei Guu, Can Jiao, Jieting Zhang, Jialin Fan, Liye Zou, Xin Yu, Xinli Chi, Philippe De Timary, Ruud Van Winkel, Bernardo Ng, Edilberto Peña De León, Ramon Arellano, Raquel Roman, Thelma Sanchez, Larisa Movina, Pedro Morgado, Sofia Brissos, Oleg Aizberg, Anna Mosina, Damir Krinitski, James Mugisha, Dena Sadeghi-Bahmani, Farshad Sheybani, Masoud Sadeghi, Samira Hadi, Serge Brand, Antonia Errazuriz, Nicolas Crossley, Dragana Ignjatovic Ristic, Carlos López-Jaramillo, Dimitris Efthymiou, Praveenlal Kuttichira, Roy Abraham Kallivayalil, Afzal Javed, Muhammad Iqbal Afridi, Bawo James, Omonefe Joy Seb-Akahomen, Jess Fiedorowicz, Jeff Daskalakis, Lakshmi N Yatham, Lin Yang, Tarek Okasha, Aïcha Dahdouh, Jari Tiihonen, Jae Il Shin, Jinhee Lee, Ahmed Mhalla, Lotfi Gaha, Takoua Brahim, Kuanysh Altynbekov, Nikolay Negay, Saltanat Nurmagambetova, Yasser Abu Jamei, Mark Weiser, Christoph U Correll

Faculty, Staff and Students Publications

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ2, penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with …

Efficacy Of Letermovir For Cytomegalovirus Prophylaxis Following Alemtuzumab T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplant, Ibrahim N Muhsen, Kristen E Shaver, Tao Wang, Mengfen Wu, Premal Lulla, Carlos A Ramos, Rammurti T Kamble, Helen E Heslop, George Carrum, Laquisa C Hill

Faculty, Staff and Students Publications

In vivo T-cell depletion (TCD) using alemtuzumab decreases the risk of Graft vs Host Disease (GvHD) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, this approach increases the risk of infections post-allo-HSCT, including Cytomegalovirus (CMV). Letermovir is approved for the use in CMV prophylaxis post-allo-HSCT. Few studies have investigated the efficacy of letermovir in patients receiving alemtuzumab. This is a single-center retrospective study describing our institutional experience using letermovir in recipients of alemtuzumab TCD allo-HSCT from unrelated donors (URD). The primary outcome was the cumulative incidence of significant CMV infection (defined as viremia leading to preemptive antiviral therapy …

The Long Road Of Drug Development For Endometriosis – Pains, Gains, And Hopes, Zian Liao, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease …

Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard

Faculty, Staff and Students Publications

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young …

Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which …

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas

Faculty, Staff and Students Publications

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and …

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …

Lack Of Association Of First And Second-Line Medication Dosing And Progression To Refractory Status Epilepticus In Children, Cristina Barcia Aguilar, Marta Amengual-Gual, J Nicholas Brenton, Kevin E Chapman, Justice Clark, William D Gaillard, Joshua L Goldstein, Howard P Goodkin, Robert Kahoud, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Eric T Payne, Craig A Press, Latania Reece, Tristan T Sands, Kumar Sannagowdara, Theodore Sheehan, Renée A Shellhaas, Robert C Tasker, Mark S Wainwright, Bo Zhang, Tobias Loddenkemper

Faculty, Staff and Students Publications

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.

Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given …

Parental Report Of Indoor Air Pollution Is Associated With Respiratory Morbidities In Bronchopulmonary Dysplasia, Jessica L Rice, Joseph M Collaco, Michael C Tracy, Catherine A Sheils, Lawrence M Rhein, Antonia P Popova, Paul E Moore, Audrey N Miller, Winston M Manimtim, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Julie L Fierro, Manvi Bansal, Eric D Austin, Brianna Aoyama, Stamatia Alexiou, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Joanne M Lagatta, Mehtap Haktanir Abul, A Ioana Cristea, Christopher D Baker, Steven H Abman, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

Objective: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative.

Study design: A cross-sectional study was performed among participants < 3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks.

Results: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, …

Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily

Faculty, Staff and Students Publications

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was …

Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne

Faculty, Staff and Students Publications

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Method: Qualitative interviews were conducted with veterans (n=15) with PTSD who had received at least 2 sessions of a TF-EBP.

Measures: Survey …

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …

Performance Of Formulas Included In The Escrs Intraocular Lens Power Calculator, Janusz Skrzypecki, Douglas D Koch, Li Wang

Faculty, Staff and Students Publications

Purpose: To compare the refractive prediction errors (PEs) of formulas included in the ESCRS intraocular lens (IOL) power calculator to aid in informed decisions on IOL power selection based on the output of this tool.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Retrospective case-series.

Methods: 748 eyes of 748 patients after implantation of 1 of 3 lenses were included, single-piece: the SN60WF, PCB00/ZCB00 and 3-piece: MA60MA. IOL constants recommended by the calculator were used for the study. We performed analysis for the whole dataset, short (< 22 mm) and long eyes (>25 mm) as well as in subgroups based on the …

Modification Of A Parent-Report Sleep Scale For Individuals With Cdkl5 Deficiency Disorder: A Psychometric Study, Jacinta M Saldaris, Scott Demarest, Peter Jacoby, Heather E Olson, Kiran Maski, Elia Pestana-Knight, Dana Price, Rajsekar Rajaraman, Bernhard Suter, Judith Weisenberg, Helen Leonard, Eric D Marsh, Tim A Benke, Jenny Downs

Faculty, Staff and Students Publications

Study objectives: Sleep difficulties are common in CDKL5 deficiency disorder, a developmental and epileptic encephalopathy. This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Somnolence (DOES), and Sleep Breathing Disorders domains of the Sleep Disturbance Scale for Children for CDKL5 deficiency disorder.

Methods: A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a United States Centers of Excellence clinic or registered with the International CDKL5 Disorder Database.

Results: The median age was 10.3 years (range 3.2-40.7 years) and 105 (84%) …

Assessing The Predictive Power Of Nutritional Indices On All-Cause And Cardiovascular Mortality In Hemodialysis Patients: A Longitudinal Study, Qian Wang, Zengchun Ye, Jialing Rao, Wenbo Zhao, Jianqiang Liu, Yanru Chen, Juncheng Xiang, Xin Zhen, Jiawen Li, Yunfang Zhang, Xianrui Dou, Zhaoyong Hu, Jun Zhang, Hui Peng

Faculty, Staff and Students Publications

BACKGROUND AND HYPOTHESIS: The prognostic value of nutritional scoring tools in assessing the relationship between nutritional status and prognosis in hemodialysis patients is unclear. This multicenter retrospective cohort study compared the Prognostic Nutritional Index (PNI), Controlling Nutritional Status scores (CONUT), and Geriatric Nutritional Risk Index (GNRI) for predictive accuracy of all-cause and cardiovascular mortality, especially the impact of dynamic changes over time on prognosis.

METHODS: Hemodialysis patients from four hospitals were included. Laboratory data and nutrition scores were collected at the initiation of dialysis, and at 6th, 12th, and 18th months after dialysis initiation. A joint model analyzed the relationship …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Implementation Of Delirium Screening In The Emergency Department: A Qualitative Study With Early Adopters, Anita N Chary, Annika R Bhananker, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Kyler M Godwin, Aanand D Naik, Christopher R Carpenter, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

Introduction: Delirium affects 15% of older adults presenting to emergency departments (EDs) but is detected in only one-third of cases. Evidence-based guidelines for ED delirium screening exist, but are underutilized. Frontline staff perceptions about delirium and time and resource constraints are known barriers to ED delirium screening uptake. Early adopters of ED delirium screening can offer valuable lessons about successful implementation.

Methods: We conducted semi-structured interviews with clinician-administrators leading ED delirium screening initiatives from 20 EDs in the United States and Canada. Interviews focused on experiences of planning and implementing ED delirium screening. Interviews lasted 15 to 50 minutes and …

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin P Zachariah, Tavleen Singh, Shannon Collinson, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson

Faculty, Staff and Students Publications

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition.

Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition …

Temporal Trends In Mortality Related To Stroke And Atrial Fibrillation In The United States: A 21-Year Retrospective Analysis Of Cdc-Wonder Database, Owais Ahmad, Hanzala Ahmed Farooqi, Isra Ahmed, Adeena Jamil, Rayyan Nabi, Irfan Ullah, Abdul Wali Khan, Raheel Ahmed, Mahboob Alam, Bernardo Cortese, Mamas A Mamas

Faculty, Staff and Students Publications

Aims: Atrial Fibrillation (AF) is one of the most strongly associated risk factors for stroke. Our study aims to analyze changes in mortality from 1999 to 2020 in patients with AF and stroke.

Methods: Using the Centre for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER), we retrospectively analyzed annual age-adjusted mortality rates (AAMR) per million from 1999 to 2020 in stroke patients with AF. Temporal trends were analyzed, and Annual Percentage Change (APC) was calculated using the JoinPoint regression model across variations in demographics (sex, race) and regional subgroups.

Results: Around 490 000 deaths were reported …

Infant-Derived Human Nasal Organoids Exhibit Relatively Increased Susceptibility, Epithelial Responses, And Cytotoxicity During Rsv Infection, Gina M Aloisio, Divya Nagaraj, Ashley M Murray, Emily M Schultz, Trevor Mcbride, Letisha Aideyan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Anubama Rajan, Amal Kambal, Hannah L Johnson, Elina Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

Background: Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.

Methods: We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.

Results: Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. …

Families’ Experiences Accessing Care After Genomic Sequencing In The Pediatric Cancer Context: “It’S Just Been A Big Juggle”, Blake Vuocolo, Amanda M Gutierrez, Jill O Robinson, Alva M Recinos, Lauren R Desrosiers, Mary A Majumder, Juan Carlos Bernini, Jonathan Gill, Timothy Griffin, Gail E Tomlinson, Kelly Vallance, Amy L Mcguire, D Williams Parsons, Sharon E Plon, Sarah Scollon

Faculty, Staff and Students Publications

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing …

A Reproducible Pipeline For Parcellation Of The Anterior Limb Of The Internal Capsule, Karianne Sretavan, Henry Braun, Zoe Liu, Daniel Bullock, Tara Palnitkar, Remi Patriat, Jayashree Chandrasekaran, Samuel Brenny, Matthew D Johnson, Alik S Widge, Noam Harel, Sarah R Heilbronner

Faculty, Staff and Students Publications

Background: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions.

Methods: Following algorithm development and refinement, we analyzed 43 …

A New Ex Vivo Model System To Analyze Factors Affecting The Integrity Of Fetal Membranes In Fetoscopic Surgery, Serjosha Robmann, Raoul Hopf, Costanza Giampietro, Lukas Moser, Alexandra Dolder, Magdalena Sanz Cortes, Martin Ehrbar, Nicole Ochsenbein, Jan Deprest, Edoardo Mazza

Faculty, Staff and Students Publications

We developed an ex vivo model system to analyze the influence of relevant environmental and mechanical factors potentially affecting the integrity of fetal membranes during fetoscopic surgery. The set-up exposes amniochorion membranes to insufflation at predefined levels of gas pressure, flow, humidity, and temperature. Change in fetal membranes stiffness is quantified during the phase mimicking surgery through measurement of membranes' strain in response to cyclic overpressure. The trocar induced perforation creates a mechanical weakness whose stability is assessed by increasing the insufflation pressure until membrane rupture. Damage of the epithelial cells lining the amnion is assessed through live-dead staining. Initial …

Sitravatinib In Patients With Solid Tumors Selected By Molecular Alterations: Results From A Phase Ib Study, Lyudmila Bazhenova, Douglas R Adkins, Et Al.

2020-Current year OA Pubs

No abstract provided.