Digital Commons Network^™

Development Of Food Pattern Recommendations For Infants And Toddlers 6-24 Months Of Age To Support The Dietary Guidelines For Americans, 2020-2025, Kathryn G Dewey, Tusarebecca Pannucci, Kellie O Casavale, Teresa A Davis, Sharon M Donovan, Ronald E Kleinman, Elsie M Taveras, Regan L Bailey, Rachel Novotny, Barbara O Schneeman, Jamie Stang, Janet De Jesus, Eve E Stoody

Children’s Nutrition Research Center Staff Publications

Background: Developing food-based dietary guidelines (FBDGs) for infants and toddlers is a complex task that few countries have attempted.

Objectives: Our objectives are to describe the process of food pattern modeling (FPM) conducted to develop FBDGs for the Dietary Guidelines for Americans, 2020-2025 for infants 6 to <12 mo and toddlers 12 to <24 mo of age, as well as the implications of the results and areas needing further work.

Methods: The US 2020 Dietary Guidelines Advisory Committee, with the support of federal staff, conducted FPM analyses using 5 steps: 1) identified energy intake targets; 2) established nutritional goals; 3) identified food groupings and expected amounts, using 3 options for the amount of energy from human milk in each age interval; 4) estimated …

Immune Responses To Injury And Their Links To Eye Disease., Mary Ann Stepp, A Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. While the purpose of these immune responses is reparative or protective, cytokines released by immune cells compromise visual acuity by inducing inflammation and fibrosis. The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact …

Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report On 30 Patients, Hasan Hashem, Giorgia Bucciol, Seza Ozen, Sule Unal, Ikbal Ok Bozkaya, Nurten Akarsu, Mervi Taskinen, Minna Koskenvuo, Janna Saarela, Dimana Dimitrova, Dennis D. Hickstein, Amy P. Hsu, Steven M. Holland, Robert Krance, Ghadir Sasa, Ashish R. Kumar, Ingo Müller, Monica Abreu De Sousa, Selket Delafontaine, Leen Moens, Florian Babor, Federica Barzaghi, Maria Pia Cicalese, Robbert Bredius, Joris Van Montfrans, Valentina Baretta, Simone Cesaro, Polina Stepensky, Neven Benedicte, Despina Moshous, Guillaume Le Guenno, David Boutboul, Jignesh Dalal, Joel P. Brooks, Elif Dokmeci, Jasmeen Dara, Carrie L. Lucas, Sophie Hambleton, Keith Wilson, Stephen Jolles, Yener Koc, Tayfun Güngör, Caroline Schnider, Fabio Candotti, Sandra Steinmann, Ansgar Schulz, Chip Chambers, Michael Hershfield, Amanda Ombrello, Jennifer A. Kanakry, Isabelle Meyts

Pediatrics Research and Scholarship

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.

METHODS: We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).

RESULTS: Thirty DADA2 patients …

Structure Of Venezuelan Equine Encephalitis Virus In Complex With The Ldlrad3 Receptor, Katherine Basore, Hongming Ma, Natasha M Kafai, Samantha Mackin, Arthur S Kim, Christopher A Nelson, Michael S Diamond, Daved H Fremont

Open Access Publications

LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)

Dicer1 Tumor Predisposition Syndrome: An Evolving Story Initiated With The Pleuropulmonary Blastoma, Iván A González, Douglas R Stewart, Kris Ann P Schultz, Amanda P Field, D Ashley Hill, Louis P Dehner

Open Access Publications

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation …

Bone Mineral Density Changes Associated With Pregnancy, Lactation, And Medical Treatments In Premenopausal Women And Effects Later In Life., Nelson B Watts, Neil Binkley, Charlotte D Owens, Ayman Al-Hendy, Elizabeth E Puscheck, Mohamad Shebley, William Schlaff, Md, James A Simon

Department of Obstetrics and Gynecology Faculty Papers

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone …

Pancreatic Differentiation Of Stem Cells Reveals Pathogenesis Of A Syndrome Of Ketosis-Prone Diabetes, Diane Yang, Sanjeet Patel, Wojciech J Szlachcic, Jolanta Chmielowiec, Diane Scaduto, Nagireddy Putluri, Arun Sreekumar, James Suliburk, Michael Metzker, Ashok Balasubramanyam, Malgorzata Borowiak

Faculty, Staff and Students Publications

Genetic analysis of an adult patient with an unusual course of ketosis-prone diabetes (KPD) and lacking islet autoantibodies demonstrated a nucleotide variant in the 5′-untranslated region (UTR) of PDX1, a β-cell development gene. When differentiated to the pancreatic lineage, his induced pluripotent stem cells stalled at the definitive endoderm (DE) stage. Metabolomics analysis of the cells revealed that this was associated with leucine hypersensitivity during transition from the DE to the pancreatic progenitor (PP) stage, and RNA sequencing showed that defects in leucine-sensitive mTOR pathways contribute to the differentiation deficiency. CRISPR/Cas9 manipulation of the PDX1 variant demonstrated that it …

Advances In Optical Gastrointestinal Endoscopy: A Technical Review, Yubo Tang, Sharmila Anandasabapathy, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user-friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light-tissue interaction at macroscopic and microscopic scales, complementing …

Using Increased Trust In Medical Researchers To Increase Minority Recruitment: The Recruit Cluster Randomized Clinical Trial, Barbara C Tilley, Arch G Mainous, Rossybelle P Amorrortu, M Diane Mckee, Daniel W Smith, Ruosha Li, Stacia M Desantis, Sally W Vernon, Gary Koch, Marvella E Ford, Vanessa Diaz, Jennifer Alvidrez

Faculty, Staff and Student Publications

While extensive literature exists on barriers and strategies to increase minority participation in clinical trials, progress is limited. Few strategies were evaluated in randomized trials. We studied the impact of RECRUIT, a trust-based, cluster randomized minority recruitment trial layered on top of four traditional NIH-funded parent trials (BMT CTN, CABANA, PACES, STEADY-PD III; fifty specialty sites). RECRUIT was conducted from July 2013 through April 2017. Intervention sites implemented trust-based approaches customized to individual sites, promoting relationships between physician-investigators and minority-serving physicians and their minority patients. Control sites implemented only parent trials' recruitment procedures. Adjusting for within-site clustering, we detected no …

A Novel Imputation Approach For Sharing Protected Public Health Data, Elizabeth A Erdman, Leonard D Young, Dana L Bernson, Cici Bauer, Kenneth Chui, Thomas J Stopka

Faculty, Staff and Student Publications

Objectives. To develop an imputation method to produce estimates for suppressed values within a shared government administrative data set to facilitate accurate data sharing and statistical and spatial analyses.

Methods. We developed an imputation approach that incorporated known features of suppressed Massachusetts surveillance data from 2011 to 2017 to predict missing values more precisely. Our methods for 35 de-identified opioid prescription data sets combined modified previous or next substitution followed by mean imputation and a count adjustment to estimate suppressed values before sharing. We modeled 4 methods and compared the results to baseline mean imputation.

Results. We assessed performance by …

Barriers To Human Papillomavirus Vaccine Uptake Among Racial/Ethnic Minorities: A Systematic Review, Trisha L Amboree, Charles Darkoh

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) is associated with poor health outcomes, including cervical cancer. Racial/ethnic minority populations experience poor health outcomes associated with HPV at higher rates. A vaccine is available to protect against HPV infections and prevent HPV-related sequelae; however, vaccination rates have remained low in the United States (U.S.) population. Thus, there is an urgent need to increase the HPV vaccination rate. Moreover, little is known about barriers to HPV vaccination in racial/ethnic minority groups. This paper highlights the most recent findings on barriers experienced by these groups.

METHODS: The PubMed database was searched on July 30, 2020, for …

Real-World Assessment Of Asthma Specialist Visits Among U.S. Patients With Severe Asthma., Jessica F Most, Christopher S Ambrose, Yen Chung, James L Kreindler, Aimee Near, Stephen Brunton, Yao Cao, Huan Huang, Xiaohui Zhao

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: U.S. guidelines recommend that patients with severe asthma be referred to specialists (allergists/immunologists or pulmonologists) for systematic assessment or comanagement; however, contemporary, real-world data on the frequency and impact of specialist care among U.S. severe asthma patients are lacking.

OBJECTIVES: To quantify the frequency of asthma specialist visits among U.S. patients with severe asthma, identify patient demographic and clinical characteristics associated with specialist visits and describe health outcomes following specialist care.

METHODS: Severe asthma patients aged 6 years or older were identified between January 1, 2015, and December 31, 2017, in the IQVIA PharMetrics® Plus database of commercially insured …

Flowcharts Improve Periodontal Diagnosis By Dental And Dental Hygiene Students, Karo Parsegian, Srinivas Ayilavarapu, Tulsi Patel, Harold A Henson, Nikola Angelov

Faculty, Staff and Student Publications

BACKGROUND: In 2017, the American Academy of Periodontology and the European Federation of Periodontology updated the classification of periodontal and peri-implant diseases and conditions. The goal of the present crossover study was to develop straightforward, illustrative flowcharts and determine their impact on the accuracy and speed of diagnosing periodontal conditions by predoctoral dental students (DS) and dental hygiene students (DHS).

METHODS: Two flowcharts (a decision-tree flowchart and one based on the periodontal disease/condition entity) were developed using updated diagnostic determinants proposed by the 2017 classification. A total of 26 second-, third-, and fourth-year DS (DS2, DS3, and DS4, respectively) and …

Adjuvant Platinum-Based Chemotherapy In Radically Resected Adrenocortical Carcinoma: A Cohort Study, Otilia Kimpel, Sara Bedrose, Felix Megerle, Alfredo Berruti, Massimo Terzolo, Matthias Kroiss, Knut Mai, Olaf M Dekkers, Mouhammed Amir Habra, Martin Fassnacht

Faculty, Staff and Students Publications

BACKGROUND: After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy.

METHODS: In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias.

RESULTS: Of the 31 …

Transmission Event Of Sars-Cov-2 Delta Variant Reveals Multiple Vaccine Breakthrough Infections, Timothy Farinholt, Harsha Doddapaneni, Xiang Qin, Vipin Menon, Qingchang Meng, Ginger Metcalf, Hsu Chao, Marie-Claude Gingras, Vasanthi Avadhanula, Paige Farinholt, Charu Agrawal, Donna M Muzny, Pedro A Piedra, Richard A Gibbs, Joseph Petrosino

Faculty, Staff and Students Publications

BACKGROUND: This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health.

METHODS: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x.

RESULTS: Viral sequencing revealed an infection cluster of …

Prevention And Screening Of Hpv Malignancies, Kristina R Dahlstrom, Andrew T Day, Erich M Sturgis

Faculty, Staff and Students Publications

It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in …

4-Dimensional Intracardiac Echocardiography In Transcatheter Mitral Valve Repair With The Mitraclip System., Carlos E Sanchez, Steven J Yakubov, Gagan Singh, Jason H Rogers, Nathan H Kander, Gilbert H L Tang

Heart and Vascular Articles

No abstract provided.

Posttraumatic Stress Symptom Clusters Differentially Predict Late Positive Potential To Cocaine Imagery Cues In Trauma-Exposed Adults With Cocaine Use Disorder, Heather E Webber, Danielle A Kessler, Emma C Lathan, Margaret C Wardle, Charles E Green, Joy M Schmitz, Scott D Lane, Anka A Vujanovic

Faculty, Staff and Student Publications

BACKGROUND: While studies have investigated the effects of posttraumatic stress disorder (PTSD) symptoms on substance use, information on these associations in the context of drug cue reactivity is lacking, which can provide meaningful information about risk for relapse. The current study assessed the associations between PTSD symptom clusters and reactivity to cues in trauma-exposed adults with cocaine use disorder.

METHODS: We recorded electroencephalogram on 52 trauma-exposed participants (M

RESULTS: Linear mixed modeling indicated that higher NACM symptomatology was associated with higher LPPs to cocaine cues and higher arousal/reactivity was associated with lower LPPs to cocaine cues.

CONCLUSIONS: These results highlight …

Outcomes Of Primary Versus Revisional Robotically Assisted Laparoscopic Roux-En-Y Gastric Bypass: A Multicenter Analysis Of Ten-Year Experience, Pouya Iranmanesh, John Fam, Thomas Nguyen, David Talarico, Kavita D Chandwani, Kulvinder S Bajwa, Melissa M Felinski, Leon V Katz, Sheilendra S Mehta, Stephan R Myers, Brad E Snyder, Peter A Walker, Todd D Wilson, Angielyn R Rivera, Connie L Klein, Shinil K Shah, Erik B Wilson

Faculty, Staff and Student Publications

BACKGROUND: Postoperative morbidity after laparoscopic bariatric surgery is considered higher for patients undergoing revisional versus primary procedures. The objective of this retrospective cohort study was to compare outcomes between patients undergoing primary versus revisional robotically assisted laparoscopic (RAL) Roux-en-Y gastric bypass (RYGB).

METHODS: Data of all patients who underwent RAL primary and revisional RYGB between 2009 and 2019 at two accredited, high-volume bariatric surgery centers-the Memorial Hermann - Texas Medical Center, Houston, TX, and the Tower Health, Reading Hospital, Reading, PA, were analyzed. Primary outcomes were early (< 30 days) and overall postoperative complications. Secondary outcomes included intraoperative complications, operative times, conversions to laparotomy, length of hospital stay, early (< 30 days) postoperative readmissions and deaths.

RESULTS: Data of 1072 patients were analyzed, including 806 primary and 266 …

Safety, Pharmacokinetics And Antiviral Activity Of Pgt121, A Broadly Neutralizing Monoclonal Antibody Against Hiv-1: A Randomized, Placebo-Controlled, Phase 1 Clinical Trial, Kathryn E Stephenson, Boris Julg, C Sabrina Tan, Rebecca Zash, Stephen R Walsh, Charlotte-Paige Rolle, Ana N Monczor, Sofia Lupo, Huub C Gelderblom, Jessica L Ansel, Diane G Kanjilal, Lori F Maxfield, Joseph Nkolola, Erica N Borducchi, Peter Abbink, Jinyan Liu, Lauren Peter, Abishek Chandrashekar, Ramya Nityanandam, Zijin Lin, Alessandra Setaro, Joseph Sapiente, Zhilin Chen, Lisa Sunner, Tyler Cassidy, Chelsey Bennett, Alicia Sato, Bryan Mayer, Alan S Perelson, Allan Decamp, Frances H Priddy, Kshitij Wagh, Elena E Giorgi, Nicole L Yates, Roberto C Arduino, Edwin Dejesus, Georgia D Tomaras, Michael S Seaman, Bette Korber, Dan H Barouch

Faculty, Staff and Student Publications

Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg

Working With Fellows Improves Adenoma Detection Rate During Screening Colonoscopies., Mark M Aloysius, Hemant Goyal, Niraj James Shah, Abhilash Perisetti Md, Benjamin Tharian

Other Specialties

No abstract provided.

Perspectives From The Society For Pediatric Research: Advice On Sustaining Science And Mentoring During Covid-19, Catherine S Forster, Suong T Nguyen, Weston T Powell, Daniel J Moore, Jacqueline Ho, Melvin B Heyman, Tara L Wenger, Fernando Gonzalez, Margaret Hostetter, Andrew Nowalk, Caroline E Rassbach, Debra Boyer, Pnina Weiss, Rebecca L Blankenburg, Jordan S Orange, Kate G Ackerman, Audrea M Burns, National Pediatric Physician-Scientist Collaborative Workgroup

Faculty, Staff and Students Publications

The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four …

Protocol For Draup: A Deimplementation Programme To Decrease Routine Chest Radiographs After Central Venous Catheter Insertion, Enyo Ablordeppey, Byron Powell, Virginia Mckay, Shannon Keating, Aimee James, Christopher Carpenter, Marin Kollef, Richard Griffey

Open Access Publications

INTRODUCTION: Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention.

METHODS: The intervention is a deimplementation programme called DRAUP (

ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data …

Activation Of The Innate Immune System In Children With Irritable Bowel Syndrome Evidenced By Increased Fecal Human Β-Defensin-2, Robert J Shulman, Sridevi Devaraj, Margaret Heitkemper

Children’s Nutrition Research Center Staff Publications

Background & aims: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation.

Methods: Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care.

Results: β-defensin-2 concentration was greater in children with IBS (P = .003) and …

Organophosphate Pesticides And Progression Of Chronic Kidney Disease Among Children: A Prospective Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Kurunthachalam Kannan, Adela Jing Li, Morgan Robinson, Bradley A. Warady, Susan Furth, Howard Trachtman, Leonardo Trasande

Manuscripts, Articles, Book Chapters and Other Papers

Background: Growing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.

Objectives: The objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.

Methods: This study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over …

Rare Variants In Kdr, Encoding Vegf Receptor 2, Are Associated With Tetralogy Of Fallot., Doris Škorić-Milosavljević, Najim Lahrouchi, Fernanda M. Bosada, Gregor Dombrowsky, Simon G. Williams, Robert Lesurf, Fleur V Y Tjong, Roddy Walsh, Ihssane El Bouchikhi, Jeroen Breckpot, Enrique Audain, Aho Ilgun, Leander Beekman, Ilham Ratbi, Alanna Strong, Maximilian Muenke, Solveig Heide, Alison M. Muir, Mariam Hababa, Laura A. Cross, Dihong Zhou, T Pastinen, German Competence Network For Congenital Heart Defects, Elaine Zackai, Samir Atmani, Karim Ouldim, Najlae Adadi, Katharina Steindl, Anita Rauch, David Brook, Anna Wilsdon, Irene Kuipers, Nico A. Blom, Barbara J. Mulder, Heather C. Mefford, Boris Keren, Pascal Joset, Paul Kruszka, Isabelle Thiffault, Sarah E. Sheppard, Amy Roberts, Elisabeth M. Lodder, Bernard D. Keavney, Sally-Ann B. Clur, Seema Mital, Marc-Philip Hitz, Vincent M. Christoffels, Alex V. Postma, Connie R. Bezzina

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear.

Methods: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF.

Results: Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in …

Providing Real-Time Resources In Support Of Lgbtq+ And Hiv+ Populations As Information Experts On The Echo Hub Team: A Case Report., Laura Menard, Chelsea Misquith

Project ECHO Bibliography

Background: Project ECHO (Extension for Community Healthcare Outcomes) is a telehealth initiative that aims to reduce disparities in delivery of health care by leveraging technology and local expertise to provide guidance on specialized subjects to health care providers across the world. In 2018, a new ECHO hub convened in Indianapolis with a focus on health care for individuals in the lesbian, gay, bisexual, trans, and queer (LGBTQ+) populations. This ECHO iteration was one of the first of its kind and would soon be followed by a new human immunodeficiency virus (HIV) ECHO as well.

Case Presentation: In a novel approach, …

Growth Rates Of Infants Randomized To Continuous Positive Airway Pressure Or Intubation After Extremely Preterm Birth, Ariel A. Salas, Waldemar A. Carlo, Barbara T. Do, Edward F. Bell, Abhik Das, Krisa P. Van Meurs, Brenda B. Poindexter, Seetha Shankaran, Noelle Younge, Kristi L. Watterberg, Rosemary D. Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants.

STUDY DESIGN: EPT infants (24

RESULTS: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well …

Ethics Of Ai In Pathology: Current Paradigms And Emerging Issues, Chhavi Chauhan, Rama R. Gullapalli

Pathology Research and Scholarship

Deep learning has rapidly advanced artificial intelligence (AI) and algorithmic decision-making (ADM) paradigms, affecting many traditional fields of medicine, including pathology, which is a heavily data-centric specialty of medicine. The structured nature of pathology data repositories makes it highly attractive to AI researchers to train deep learning models to improve health care delivery. Additionally, there are enormous financial incentives driving adoption of AI and ADM due to promise of increased efficiency of the health care delivery process. AI, if used unethically, may exacerbate existing inequities of health care, especially if not implemented correctly. There is an urgent need to harness …

Clinical Trial And Postmarketing Safety Of Onasemnogene Abeparvovec Therapy, John W Day, Jerry R Mendell, Eugenio Mercuri, Richard S Finkel, Kevin A Strauss, Aaron Kleyn, Sitra Tauscher-Wisniewski, Francis Fonyuy Tukov, Sandra P Reyna, Deepa H Chand

2020-Current year OA Pubs

INTRODUCTION: This is the first description of safety data for intravenous onasemnogene abeparvovec, the only approved systemically administered gene-replacement therapy for spinal muscular atrophy.

OBJECTIVE: We comprehensively assessed the safety of intravenous onasemnogene abeparvovec from preclinical studies, clinical studies, and postmarketing data.

METHODS: Single-dose toxicity studies were performed in neonatal mice and juvenile or neonatal cynomolgus nonhuman primates (NHPs). Data presented are from a composite of preclinical studies, seven clinical trials, and postmarketing sources (clinical trials, n = 102 patients; postmarketing surveillance, n = 665 reported adverse event [AE] cases). In clinical trials, safety was assessed through AE monitoring, vital-sign …