Medical Specialties Commons^™

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …

The Concentration Of Total Nucleated Cells In Harvested Bone Marrow For Transplantation Has Decreased Over Time., Nicole L. Prokopishyn, Brent R. Logan, Deidre M. Kiefer, Jennifer A. Sees, Pintip Chitphakdithai, Ibrahim A. Ahmed, Paolo N. Anderlini, Amer M. Beitinjaneh, Christopher Bredeson, Jan Cerny, Saurabh Chhabra, Andrew Daly, Miguel Angel Diaz, Nosha Farhadfar, Haydar A. Frangoul, Siddhartha Ganguly, Dennis A. Gastineau, Usama Gergis, Gregory A. Hale, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Hemant S. Murthy, Maxim Norkin, Richard F. Olsson, Mona Papari, Bipin N. Savani, Jeffrey Szer, Edmund K. Waller, Baldeep Wirk, Jean A. Yared, Michael A. Pulsipher, Nirali N. Shah, Galen E. Switzer, Paul V. O'Donnell, Dennis L. Confer, Bronwen E. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact …

Comparison Of Cyanoacrylate Closure And Radiofrequency Ablation For The Treatment Of Incompetent Great Saphenous Veins: 36-Month Outcomes Of The Veclose Randomized Controlled Trial., Nick Morrison, Raghu Kolluri, Michael Vasquez, Monte Madsen, Andrew Jones, Kathleen Gibson

Heart and Vascular Articles

OBJECTIVE: To evaluate the 36-month efficacy and safety of cyanoacrylate closure for the treatment of incompetent great saphenous veins in comparison with radiofrequency ablation.

METHODS: In this multicenter, prospective, randomized controlled trial, 222 symptomatic subjects with incompetent great saphenous veins were assigned to either cyanoacrylate closure or radiofrequency ablation. The primary endpoint, complete closure of the target great saphenous vein, was determined using duplex ultrasound examination starting from three-month visit.

RESULTS: At month 36, the great saphenous vein closure rates were 94.4% for the cyanoacrylate closure group and 91.9% for the radiofrequency ablation group. Stable improvement in symptoms and quality …

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 …

Pathologic Gene Network Rewiring Implicates Ppp1r3a As A Central Regulator In Pressure Overload Heart Failure., Pablo Cordero, Victoria N Parikh, Elizabeth T Chin, Ayca Erbilgin, Michael J Gloudemans, Ching Shang, Yong Huang, Alex C Chang, Kevin S Smith, Frederick Dewey, Kathia Zaleta, Michael Morley, Jeff Brandimarto, Nicole Glazer, Daryl Waggott, Aleksandra Pavlovic, Mingming Zhao, Christine S Moravec, W H Wilson Tang, Jamie Skreen, Christine Malloy, Sridhar Hannenhalli, Hongzhe Li, Scott Ritter, Mingyao Li, Daniel Bernstein, Andrew Connolly, Hakon Hakonarson, Aldons J Lusis, Kenneth B Margulies, Anna A Depaoli-Roach, Stephen B Montgomery, Matthew T Wheeler, Thomas Cappola, Euan A Ashley

Articles, Abstracts, and Reports

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and …

Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …

Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme

Articles, Abstracts, and Reports

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 …

Real-World Treatment Patterns And Adverse Events In Metastatic Renal Cell Carcinoma From A Large Us Claims Database., Sumanta Pal, Jun Gong, Shivani K Mhatre, Shih-Wen Lin, Andy Surinach, Sarika Ogale, Rini Vohra, Herschel Wallen, Daniel George

Articles, Abstracts, and Reports

BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC.

METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to …

Unanticipated Admissions To Paediatric Cardiac Critical Care After Cardiac Catheterisations., Erin Peebles, Michael R Miller, Lee N Benson, Tilman Humpl

Paediatrics Publications

OBJECTIVES: Cardiac catheterisation is commonly used for diagnosis and therapeutic interventions in paediatric cardiology. The inherent risk of the procedure can result in unanticipated admissions to critical care. Our goals were to provide a qualitative description of characteristics and evaluation of children admitted unexpectedly to the cardiac critical care unit (CCCU).

METHODS: A retrospective single centre review of cardiac catheterisation procedures was done between 1 January, 2003 and 30 April, 2013.

RESULTS: Of 9336 cardiac catheterisations performed, 146 (1.6%) were admitted from the catheterisation laboratory to the CCCU and met inclusion criteria. Of these 146 patients, 117 (1.3%) met criteria …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

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 …

Incidence And Predictors Of Obstructive Coronary Artery Disease And The Role Of Cardiac Troponin Assays In Patients With Unstable Angina, Sushan Yang, Nirmanmoh Bhatia, Meng Xu, John A Mcpherson

The Texas Heart Institute Journal

In a time when cardiac troponin assays are widely used to detect myocardial injury, data remain scarce concerning the incidence and predictors of substantial obstructive coronary artery disease that causes unstable angina. This retrospective single-center study included consecutive patients hospitalized for unstable angina from January 2015 through January 2016. Patients with troponin I levels above the upper reference limit and those who did not undergo angiography were excluded. Multivariate logistic regression analysis was used to identify predictors of obstructive coronary artery disease that warranted revascularization and of major adverse cardiac events up to 6 months after discharge from the hospital. …

Osborn Waves: Differential Diagnosis, Akriti G Jain, Hammad Zafar, Sanjay Jain, Jason D'Souza

The Texas Heart Institute Journal

No abstract provided.

Percutaneous Coronary Intervention For Interposed Coronary Graft Stenosis After Modified Bentall Procedure In A Teenaged Boy With Takayasu Arteritis, Hiroki Ikenaga, Satoshi Kurisu, Yasuki Kihara

The Texas Heart Institute Journal

Anastomotic occlusion of an interposed coronary artery graft after a Bentall procedure is rare and catastrophic. It can lead to myocardial infarction or sudden cardiac death. We found several reports of occlusion and stenosis of a coronary-graft anastomosis, but few describe occlusion of the interposed coronary graft itself, as evaluated with use of intracoronary ultrasonography and computed tomography. We report the case of a 17-year-old boy with Takayasu arteritis who had a myocardial infarction caused by severe ostial stenosis in an interposed left coronary graft. The graft occlusion was confirmed by results of electrocardiography, aortography, and intracoronary ultrasonography. The patient …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

Surgical Thrombectomy For Pulmonary Embolism: Updated Performance Rates And Outcomes, Fahad Alqahtani, Muhammad Bilal Munir, Sami Aljohani, Abdul Tarabishy, Ahmad Almustafa, Mohamad Alkhouli

The Texas Heart Institute Journal

Treatments for pulmonary embolism are numerous and often complex. Current data on surgical thrombectomy are important but are not readily available. We studied the National Inpatient Sample to evaluate trends in the performance rates and outcomes of surgical thrombectomy in the United States from 2003 through 2014. We think that our findings have meaningful application to the triage and risk stratification of patients who have hemodynamically significant pulmonary embolism.

Altered Detrusor Contractility And Voiding Patterns In Mice Lacking The Mechanosensitive Trek-1 Channel., Ricardo H. Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B. Meacham, Anna P. Malykhina

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.

METHODS: Adult C57BL/6 …

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.

A Prospective, Single-Arm, Multicenter Trial Of Catheter-Directed Mechanical Thrombectomy For Intermediate-Risk Acute Pulmonary Embolism: The Flare Study., Thomas Tu, Catalin Toma, Victor F Tapson, Christopher Adams, Wissam A Jaber, Mitchell Silver, Sameer Khandhar, Rohit Amin, Mitchell Weinberg, Tod Engelhardt, Monica Hunter, David Holmes, Glenn Hoots, Hussam Hamdalla, Robert L Maholic, Scott M Lilly, Kenneth Ouriel, Kenneth Rosenfield, Flare Investigators

Ambulatory and Primary Care Articles

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a prospective trial of patients with acute intermediate-risk pulmonary embolism (PE).

BACKGROUND: Catheter-directed thrombolysis has been shown to improve right ventricular (RV) function in patients with PE. However, catheter-directed thrombolysis increases bleeding risk and many patients with PE have relative and absolute contraindications to thrombolysis.

METHODS: Patients with symptomatic, computed tomography-documented PE and RV/left ventricular (LV) ratios ≥0.9 were eligible for enrollment. The primary effectiveness endpoint was core laboratory-assessed change in RV/LV ratio. The …

Antibody-Based Ticagrelor Reversal Agent In Healthy Volunteers., Deepak L. Bhatt, Charles V. Pollack, Jeffrey I. Weitz, Lisa K. Jennings, Sherry Xu, Susan E. Arnold, Bret R. Umstead, Michael C. Mays, John S. Lee

Department of Emergency Medicine Faculty Papers

BACKGROUND: Ticagrelor is an oral P2Y₁₂ inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful.

METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

Daratumumab, Bortezomib, Cyclophosphamide And Dexamethasone In Newly Diagnosed And Relapsed Multiple Myeloma: Lyra Study., Habte Yimer, Jason Melear, Edward Faber, William Bensinger, John M Burke, Mohit Narang, Don Stevens, Sriya Gunawardena, Yana Lutska, Keqin Qi, Jon Ukropec, Ming Qi, Thomas S Lin, Robert M Rifkin

Articles, Abstracts, and Reports

This United States community study evaluated the combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone (D-VCd) in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). Patients received 4-8 induction cycles of bortezomib 1·5 mg/m2 , cyclophosphamide 300 mg/m2 and dexamethasone 40 mg weekly. Intravenous daratumumab 16 mg/kg was administered as approved except for a split-first dose in Cycle 1. Eligible patients underwent autologous stem cell transplantation. All patients received ≤12 daratumumab maintenance doses monthly. Eighty-six NDMM and 14 RMM patients received ≥1 treatment dose. In NDMM patients, very good partial response or better (≥VGPR) and overall response rates after …

Evaluating The Effectiveness And Implementation Of Evidence-Based Treatment: A Multisite Hybrid Design., Jamile A Ashmore, Kirk W Ditterich, Claire C Conley, Melissa R Wright, Peggy S Howland, Kelly L Huggins, Jena Cooreman, Priscilla S Andrews, Donald R Nicholas, Lind Roberts, Larissa Hewitt, Joan N Scales, Jenny K Delap, Christine A Gray, Lynelle A Tyler, Charlotte Collins, Catherine M Whiting, Brittany M Brothers, Marlena M Ryba, Barbara L Andersen

Articles, Abstracts, and Reports

The gap between treatment development and efficacy testing to scaled up implementations of evidence-based treatment (EBT) is an estimated 20 years, and hybrid research designs aim to reduce the gap. One was used for a multisite study in cancer control, testing coprimary aims: (a) determine the feasibility and utility of a flexible EBT implementation strategy and (b) determine the clinical effectiveness of an EBT as implemented by newly trained providers. Therapists from 15 diverse sites implemented the biobehavioral intervention (BBI) for cancer patients (N = 158) as part of standard care. For implementation, therapists determined treatment format, number of …

Comparative Effectiveness Of Drugs Used To Constrict The Patent Ductus Arteriosus: A Secondary Analysis Of The Pda-Tolerate Trial (Nct01958320)., Melissa Liebowitz, Joseph Kaempf, Omer Erdeve, Ali Bulbul, Stellan Håkansson, Johanna Lindqvist, Aijaz Farooqi, Anup Katheria, Jason Sauberan, Jaideep Singh, Kelly Nelson, Andrea Wickremasinghe, Lawrence Dong, Denise C Hassinger, Susan W Aucott, Madoka Hayashi, Anne Marie Heuchan, William A Carey, Matthew Derrick, Ilene Sue Wolf, Amy Kimball, Meera Sankar, Tina Leone, Jorge Perez, Arturo Serize, Ronald I Clyman

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.

METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).

RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen …

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 …

Cervical Posterior Longitudinal Ligament Ossification : Microscopy-Assisted Anterior Corpectomy And Fusion., Wanyi Wang, Tao Ding, James Harrop, Huilin Yang, Xiaofeng Gu, Dehong Feng, Yafeng Zhang, Hao Liu, Fenglin Tang, Yuntao Xue, Miao Lu, Chao Wu

Department of Neurosurgery Faculty Papers

OBJECTIVE: To explore the clinical efficacy and safety of microscopy-assisted anterior corpectomy and fusion for cervical ossification of the posterior longitudinal ligament (OPLL).

METHODS: A retrospective review of 32 cervical OPLL patients who underwent microscopy-assisted anterior corpectomy and fusion from June 2012 to March 2017 was carried out. Patients were evaluated with outcome metrics: Japanese Orthopaedic Association (JOA) scores (17 points method), visual analog scale (VAS), and radiographic parameters of the lordotic angle. The complications during treatment and follow-up were recorded.

RESULTS: This study included 32 patients (15 males and 17 females) with a mean age of 58.3 ± 2.9 …

Comparative Effectiveness Of Intensity Modulated Radiation Therapy To 3-Dimensional Conformal Radiation In Locally Advanced Lung Cancer: Pathological And Clinical Outcomes., Sarit Appel, Jair Bar, Alon Ben-Nun, Marina Perelman, Dror Alezra, Damien Urban, Maoz Ben-Ayun, Nir Honig, Efrat Ofek, Tamar Katzman, Amir Onn, Sumit Chatterji, Sergey Dubinski, Lev Tsvang, Shira Felder, Judith Kraitman, Ory Haisraely, Tatiana Rabin Alezra, Sivan Lieberman, Edith M. Marom, Nir Golan, David Simansky, Zvi Symon, Yaacov Richard Lawrence

Department of Radiation Oncology Faculty Papers

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy.

METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) …