Medical Specialties Commons^™

Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton

Faculty, Staff and Students Publications

Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …

Fat And Fat-Free Mass Index References In Children And Young Adults: Assessments Along Racial And Ethnic Lines, Roman J Shypailo, William W Wong

Children’s Nutrition Research Center Staff Publications

Background: Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children.

Objectives: Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups.

Methods: Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass …

Reliability And Validity Of The English Version Of The Aospine Prost (Patient Reported Outcome Spine Trauma), Said Sadiqi, Marcel F Dvorak, Alex R. Vaccaro, Gregory D. Schroeder, Marcel W Post, Lorin M Benneker, Frank Kandziora, S Rajasekaran, Klaus J Schnake, Emiliano N Vialle, F Cumhur Oner

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Multicenter validation study.

OBJECTIVE: The aim of this study was to translate and adapt the AOSpine PROST (Patient Reported Outcome Spine Trauma) into English, and test its psychometric properties among North-American spine trauma patients.

SUMMARY OF BACKGROUND DATA: In the absence of an outcome instrument specifically designed and validated for traumatic spinal column injury patients, it is difficult to measure the effect size of various treatment options. The AOSpine Knowledge Forum Trauma initiated a project and developed the AOSpine PROST consisting of 19 items.

METHODS: Patients were recruited from two level-1 North-American trauma centers. For concurrent validity, next …

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Faculty, Staff and Students Publications

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …

Mechanical Prosthetic Valve Sparing For Aortic Root Abscess Complicated By Infective Endocarditis, Ahmed Ahmed, Ayman Ammar, Yasser Elnahas, Mohammed Abd Al Jawad

The Texas Heart Institute Journal

Aortic root abscess complicated by infective endocarditis of a mechanical prosthetic valve is associated with morbidity and death. We retrospectively report our experience with a valve-sparing technique for managing this condition.

From October 2014 through November 2017, 41 patients at our center underwent surgery for aortic root abscess complicated by infective endocarditis of a mechanical prosthetic valve. Twenty (48.7%) met prespecified criteria for use of our valve-sparing technique after careful assessment of the mechanical valve and surrounding tissues. Our technique involved draining the abscess, aggressively débriding all infected and necrotic tissues, and then repairing the resulting defect by suturing a …

Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon

Paediatrics Publications

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA

RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,

CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga

Wills Eye Hospital Papers

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

OBJECTIVES: The objective of this review was to …

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Acute Maltodextrin Supplementation During Resistance Exercise, Dylan T Wilburn, Steven B Machek, Thomas D Cardaci, Paul S Hwang, Darryn S Willoughby

Faculty, Staff and Students Publications

Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with …

Network Meta-Analysis To Compare Venaseal With Other Superficial Venous Therapies For Chronic Venous Insufficiency., Raghu Kolluri, Janice Chung, Sue Kim, Nibir Nath, Bhoomika Bajaj Bhalla, Tarun Jain, Joseph Zygmunt, Alun Davies

Heart and Vascular Articles

OBJECTIVE: Several randomized controlled trials (RCTs) have compared different interventions for chronic venous insufficiency (CVI) management, but mixed comparison of these interventions is lacking. The aim of this network meta-analysis was to compare VenaSeal closure system (Medtronic, Minneapolis, Minn) with endovenous laser ablation (EVLA), radiofrequency ablation (RFA), mechanochemical ablation, sclerotherapy, and surgery for management of CVI to achieve anatomic success (complete closure of treated vein within 6 months after intervention) as the primary outcome and health-related quality of life (HRQoL; EuroQol-5 Dimension, Aberdeen Varicose Vein Questionnaire), Venous Clinical Severity Score (VCSS), pain scores, and adverse events as secondary outcomes.

METHODS: …

Histologic Abnormalities Of The Ascending Aorta: Effects On Aortic Remodeling After Intracardiac Repair Of Tetralogy Of Fallot, Ujjwal Kumar Chowdhury, Lakshmi Kumari Sankhyan, Sheil Avneesh, Ruma Ray, Mani Kalaivani, Suruchi Hasija, Abhinavsingh Chauhan

The Texas Heart Institute Journal

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables.

Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter.

Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, …

Fibrin Clots Maintain The Viability And Proliferative Capacity Of Human Mesenchymal Stem Cells: An In Vitro Study, Ryan J Warth, Paul G Shupe, Xueqin Gao, Mohammad Syed, Walter R Lowe, Johnny Huard, Christopher D Harner

Faculty, Staff and Student Publications

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

Final Two-Year Outcomes For The Sentry Bioconvertible Inferior Vena Cava Filter In Patients Requiring Temporary Protection From Pulmonary Embolism., Michael D Dake, Timothy P Murphy, Albrecht H Krämer, Michael D Darcy, Luke E Sewall, Michael A Curi, Matthew S Johnson, Frank Arena, James L Swischuk, Gary M Ansel, Mitchell J Silver, Souheil Saddekni, Jayson S Brower, Robert Mendes, Sentry Trial Investigators

Heart and Vascular Articles

PURPOSE: To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE).

MATERIALS AND METHODS: In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years.

RESULTS: The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was …

Age Of Acquisition Impacts The Brain Differently Depending On Neuroanatomical Metric, Hannah Claussenius-Kalman, Kelly A Vaughn, Pilar Archila-Suerte, Arturo E Hernandez

Faculty, Staff and Student Publications

Although researchers generally agree that a certain set of brain areas underlie bilingual language processing, there is discrepancy regarding what effect timing of language acquisition has on these regions. We aimed to investigate the neuroanatomical correlates of age of acquisition (AoA), which has been examined previously, but with inconsistent results, likely influenced by methodological differences across studies. We analyzed gray matter density, volume, and thickness using whole-brain linear models in 334 bilinguals and monolinguals. Neuroanatomical correlates of AoA differed depending on gray matter metric. Relative to early bilinguals, late bilinguals had thicker cortex in language processing and cognitive control regions, …

Clinical Mortality In A Large Covid-19 Cohort: Observational Study., M. Jarrett, S. Schultz, J. Lyall, J. Wang, L. Stier, M. De Geronimo, K. Nelson

Journal Articles

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic.

OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls.

METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, …

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

The Society Of Abdominal Radiology At 10 Years: Reflections, Status Report, And Look To The Future, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Faculty, Staff and Student Publications

CONTEXT.—: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV.

OBJECTIVES.—: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies.

DESIGN.—: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history.

RESULTS.—: Fifty-two cases (24% of all tested, …

Demographic, Clinical, And Treatment Characteristics Of The Juvenile Primary Fibromyalgia Syndrome Cohort Enrolled In The Childhood Arthritis And Rheumatology Research Alliance Legacy Registry., Jennifer E. Weiss, Kenneth N. Schikler, Alexis D. Boneparth, Mark Connelly, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: To describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics.

METHODS: Information on demographics, symptoms, functioning, and treatments recommended and tried were obtained on patients with JPFS as part of a multi-site patient registry (the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry). Data were summarized using descriptive statistics. In a subset of patients completing registry follow-up visits, changes in symptoms, pain, and functioning were evaluated using growth modeling.

RESULTS: Of the 201 patients with JPFS enrolled in the registry, most were Caucasian/White (85%), non-Hispanic …

Developing Comparative Effectiveness Studies For A Rare, Understudied Pediatric Disease: Lessons Learned From The Carra Juvenile Localized Scleroderma Consensus Treatment Plan Pilot Study., Suzanne C. Li, Robert C. Fuhlbrigge, Ronald M. Laxer, Elena Pope, Maria Ibarra, Katie Stewart, Thomas Mason, Mara L. Becker, Sandy Hong, Fatma Dedeoglu, Kathryn S. Torok, C Egla Rabinovich, Polly J. Ferguson, Marilynn Punaro, Brian M. Feldman, Tracy Andrews, Gloria C. Higgins, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases.

METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize …

Hospital Readmission Of Adolescents And Young Adults With Complex Chronic Disease., Peter Dunbar, Matt Hall, James C. Gay, Clarissa Hoover, Jessica L. Markham, Jessica L. Bettenhausen, James M. Perrin, Karen A. Kuhlthau, Morgan Crossman, Brigid Garrity, Jay G. Berry

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Adolescents and young adults (AYA) who have complex chronic disease (CCD) are a growing population that requires hospitalization to treat severe, acute health problems. These patients may have increased risk of readmission as demands on their self-management increase and as they transfer care from pediatric to adult health care practitioners.

Objective: To assess variation across CCDs in the likelihood of readmission for AYA with increasing age.

Design, Setting, and Participants: Retrospective 1-year cross-sectional study of the 2014 Agency for Healthcare Research and Quality Nationwide Readmissions Database for all US hospitals. Participants were 215 580 hospitalized individuals aged 15 to …

Evaluation Of Clinical Outcomes In An Interdisciplinary Abdominal Pain Clinic: A Retrospective, Exploratory Review., Amanda D. Deacy, Craig A. Friesen, Vincent S. Staggs, Jennifer Verrill Schurman

Manuscripts, Articles, Book Chapters and Other Papers

Background: Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement.

Aim: To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related …

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …

Abcb1 Snp Predicts Outcome In Patients With Acute Myeloid Leukemia Treated With Gemtuzumab Ozogamicin: A Report From Children's Oncology Group Aaml0531 Trial., Roya Rafiee, Lata Chauhan, Todd A. Alonzo, Yi-Cheng Wang, Ahlam Elmasry, Michael R. Loken, Jessica Pollard, Richard Aplenc, Susana Raimondi, Betsy A. Hirsch, Irwin D. Bernstein, A S. Gamis, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Gemtuzumab-ozogamicin (GO), a humanized-anti-CD33 antibody linked with the toxin-calicheamicin-γ is a reemerging and promising drug for AML. Calicheamicin a key element of GO, induces DNA-damage and cell-death once the linked CD33-antibody facilitates its uptake. Calicheamicin efflux by the drug-transporter PgP-1 have been implicated in GO response thus in this study, we evaluated impact of ABCB1-SNPs on GO response. Genomic-DNA samples from 942 patients randomized to receive standard therapy with or without addition of GO (COG-AAML0531) were genotyped for ABCB1-SNPs. Our most interesting results show that for rs1045642, patients with minor-T-allele (CT/TT) had better outcome as compared to patients with CC …

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Tisagenlecleucel Model-Based Cellular Kinetic Analysis Of Chimeric Antigen Receptor-T Cells., Andrew M. Stein, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Bruce L. Levine, Lori Tomassian, Sweta Shah, Mimi Leung, Pai-Hsi Huang, Rakesh Awasthi, Karen Thudium Mueller, Patricia A. Wood, Carl H. June

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19+ B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion. The doubling time, initial decline half-life, and terminal half-life for tisagenlecleucel were 0.78, 4.3, and 220 days, respectively. No impact of tocilizumab or …