Medicine and Health Sciences Commons^™

Treatment-Free Remission In Patients With Chronic Myeloid Leukemia Following The Discontinuation Of Tyrosine Kinase Inhibitors, Fadi G Haddad, Koji Sasaki, Ghayas C Issa, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Marina Konopleva, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney Dinardo, Nitin Jain, Naval Daver, Nicholas J Short, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Frailty Repels The Knife: The Impact Of Frailty Index On Surgical Intervention And Outcomes, Katelyn F Handley, Anil K Sood, Graziela Zibetti Dal Molin, Shannon N Westin, Larissa A Meyer, Bryan Fellman, Pamela T Soliman, Robert L Coleman, Nicole D Fleming

Faculty, Staff and Student Publications

Objective: To assess the impact of frailty in patients with ovarian cancer on surgical procedures and outcomes.

Methods: A retrospective review of patients with stage II-IV ovarian cancer from April 2013 to September 2017 was performed. Patients were triaged by laparoscopy to determine primary resectability. The adjusted modified frailty index score (amFI) was calculated and amFI ≥2 classified as high frailty. Clinical outcomes, progression free survival (PFS) and overall survival (OS) were estimated.

Results: 592 patients met inclusion criteria; amFI of 0, 1 and ≥ 2 was noted in 57%, 29%, and 14%, respectively. Patients with high frailty were less …

Interim Outcomes Of Mechanical Thrombectomy For Deep Vein Thrombosis From The All-Comer Clout Registry, David J Dexter, Luis Sanchez, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients.

METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days …

Dose-Related Effects Of Ketamine For Antidepressant-Resistant Symptoms Of Posttraumatic Stress Disorder In Veterans And Active Duty Military: A Double-Blind, Randomized, Placebo-Controlled Multi-Center Clinical Trial, Chadi G Abdallah, John D Roache, Ralitza Gueorguieva, Lynnette A Averill, Stacey Young-Mccaughan, Paulo R Shiroma, Prerana Purohit, Antoinette Brundige, William Murff, Kyung-Heup Ahn, Mohamed A Sherif, Eric J Baltutis, Mohini Ranganathan, Deepak D'Souza, Brenda Martini, Steven M Southwick, Ismene L Petrakis, Rebecca R Burson, Kevin B Guthmiller, Argelio L López-Roca, Karl A Lautenschlager, John P Mccallin, Matthew B Hoch, Alexandar Timchenko, Sergio E Souza, Charles E Bryant, Jim Mintz, Brett T Litz, Douglas E Williamson, Terence M Keane, Alan L Peterson, John H Krystal

Staff and Researcher Publications

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome …

Impact Of Coronavirus Disease 2019 Restrictions On Retinal Detachment: A Multicenter Experience, Jesse J Jung, Jonathan S Chang, Patrick R Oellers, Mohsin H Ali, Brian K Do, Joseph J Tseng, Roberto Roizenblatt, Rajeev H Muni, Christina Y Weng, Zackery B Oakey, Sean W Tsao, Soraya Rofagha, Xavier Chan, Quan V Hoang

Faculty, Staff and Students Publications

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Efficacy And Outcomes Of Faecal Microbiota Transplantation For Recurrent Clostridioides Difficile Infection In Children With Inflammatory Bowel Disease, Maribeth R Nicholson, Erin Alexander, Sonia Ballal, Zev Davidovics, Michael Docktor, Michael Dole, Jonathan M Gisser, Alka Goyal, Suchitra K Hourigan, M Kyle Jensen, Jess L Kaplan, Richard Kellermayer, Judith R Kelsen, Melissa A Kennedy, Sahil Khanna, Elizabeth D Knackstedt, Jennifer Lentine, Jeffery D Lewis, Sonia Michail, Paul D Mitchell, Maria Oliva-Hemker, Tiffany Patton, Karen Queliza, Sarah Sidhu, Aliza B Solomon, David L Suskind, Madison Weatherly, Steven Werlin, Edwin F De Zoeten, Stacy A Kahn, North American Society Of Pediatric Gastroenterology And Nutrition Faecal Microbiota Transplantation Special Interest Group

Faculty, Staff and Students Publications

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD.

METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data …

Bilateral Upper Extremity Motor Priming (Bump) Plus Task-Specific Training For Severe, Chronic Upper Limb Hemiparesis: Study Protocol For A Randomized Clinical Trial, Mary Ellen Stoykov, Olivia M Biller, Alexandra Wax, Erin King, Jacob M Schauer, Louis F Fogg, Daniel M Corcos

Department of Occupational Therapy Faculty Papers

BACKGROUND: Various priming techniques to enhance neuroplasticity have been examined in stroke rehabilitation research. Most priming techniques are costly and approved only for research. Here, we describe a priming technique that is cost-effective and has potential to significantly change clinical practice. Bilateral motor priming uses the Exsurgo priming device (Exsurgo Rehabilitation, Auckland, NZ) so that the less affected limb drives the more affected limb in bilateral symmetrical wrist flexion and extension. The aim of this study is to determine the effects of a 5-week protocol of bilateral motor priming in combination with task-specific training on motor impairment of the affected …

Up To 8-Year Follow-Up From Resonate-2: First-Line Ibrutinib Treatment For Patients With Chronic Lymphocytic Leukemia, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Steve E Coutre, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian-Yong Li, Fritz Offner, Carol Moreno, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio …

Neutrophil-To-Lymphocyte Ratios In Patients Undergoing Aortic Valve Replacement: The Partner Trials And Registries, Bahira Shahim, Alan Zajarias, Et Al

2020-Current year OA Pubs

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) …

Statins Enhance The Chemosensitivity Of R-Chop In Diffuse Large B-Cell Lymphoma, Sushanth Gouni, Paolo Strati, Gokce Toruner, Akanksha Aradhya, Ralf Landgraf, Daniel Bilbao, Francisco Vega, Nitin Kumar Agarwal

Faculty, Staff and Student Publications

The beneficial effect of statins on the anti-lymphoma activity of the rituximab-based chemotherapy regimen is controversial. Here, we retrospectively reviewed patients with naïve-treated advanced diffuse large B-cell lymphoma (DLBCL) receiving frontline R-CHOP, and for whom data regarding differential statins use was available at the time of initiation of treatment. We observe that patients treated with statins and R-CHOP experienced a significantly higher CR rate as compared to those who received R-CHOP only. We further show that patients receiving medium or high intensity statins and R-CHOP experienced a significantly higher CR as compared to those treated with R-CHOP. Six-year progression free …

Assessment Of Clinical Response Following Atezolizumab And Bevacizumab Treatment In Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial, Daniel M Halperin, Suyu Liu, Arvind Dasari, David Fogelman, Priya Bhosale, Armeen Mahvash, Jeannelyn S Estrella, Laura Rubin, Ajaykumar C Morani, Mark Knafl, Tim A Overeem, Szu-Chin Fu, Luisa M Solis, Edwin Parra Cuentas, Anuj Verma, Hong-Lei Chen, Swati Gite, Priya Subashchandrabose, Shannon Dervin, Katja Schulze, Walter C Darbonne, Cindy Yun, Ignacio I Wistuba, P Andrew Futreal, Scott E Woodman, James C Yao

Faculty, Staff and Student Publications

Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.

Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.

Design, setting, and participants: This single-arm, open-label …

Association Of Molecular Senescence Markers In Late-Life Depression With Clinical Characteristics And Treatment Outcome, Breno S Diniz, Benoit H Mulsant, Charles F Reynolds, Daniel M Blumberger, Jordan F Karp, Meryl A Butters, Ana Paula Mendes-Silva, Erica L Vieira, George Tseng, Eric J Lenze

2020-Current year OA Pubs

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted …

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K Cleary, Matthew Silviera, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy.

METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates.

RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …

Assessing Real-World Racial Differences Among Patients With Metastatic Triple-Negative Breast Cancer In Us Community Practices, Ruoding Tan, Lourenia Cassoli, Ying Yan, Vincent Shen, Bann-Mo Day, Edith P. Mitchell

Department of Medical Oncology Faculty Papers

Objective: Real-world data characterizing differences between African American (AA) and White women with metastatic triple-negative breast cancer (mTNBC) are limited. Using 9 years of data collected from community practices throughout the United States, we assessed racial differences in the proportion of patients with mTNBC, and their characteristics, treatment, and overall survival (OS).

Methods: This retrospective study analyzed de-identified data from 2,116 patients with mTNBC in the Flatiron Health database (January 2011 to March 2020). Characteristics and treatment patterns between AA and White patients with mTNBC were compared using descriptive statistics. OS was examined using Kaplan-Meier analysis and a multivariate Cox …

Belimumab For Systemic Lupus Erythematosus - Focus On Lupus Nephritis, Marlene Plüß, Silvia Piantoni, Björn Tampe, Alfred H J Kim, Peter Korsten

2020-Current year OA Pubs

In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive …

Mortality After Transcatheter Aortic Valve Replacement For Aortic Stenosis Among Patients With Malignancy: A Systematic Review And Meta-Analysis, Muhammad U Siddiqui, Omar Yacob, Joey Junarta, Ahmed K Pasha, Farouk Mookadam, Mamas A Mamas, D L Fischman

Division of Internal Medicine Faculty Papers & Presentations

Background: With advancements in cancer treatment, the life expectancy of oncology patients has improved. Thus, transcatheter aortic valve replacement (TAVR) may be considered as a feasible option for oncology patients with severe symptomatic aortic stenosis (AS). We aim to evaluate the difference in short- and long-term all-cause mortality in cancer and non-cancer patients treated with TAVR for severe AS.

Methods: Medline, PubMed, and Cochrane Central Register of Controlled Trials were searched for relevant studies. Patients with cancer who underwent treatment with TAVR for severe AS were included and compared to an identical population without cancer. The primary endpoints were short- …

Riluzole For Pediatric Patients With Treatment-Refractory Obsessive-Compulsive Disorder, Maheen Mohammad, Stuti Parikh

Rowan-Virtua Research Day

Obsessive-compulsive disorder (OCD) occurs in about 1-3% of the pediatric population, but many do not respond to standard therapies. Riluzole, a glutamate antagonist, has shown to be an effective treatment for refractory OCD in adults, however few trials have been conducted to show the effectiveness of Riluzole in children to treat refractory OCD. The study investigates the potential use of riluzole in children to treat refractory OCD.

Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath

Department of Neurology Faculty Papers

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among 17 patients (mean age …

Outstanding Outcomes In Infants With Kmt2a-Germline Acute Lymphoblastic Leukemia Treated With Chemotherapy Alone: Results Of The Children's Oncology Group Aall0631 Trial, Erin M. Guest, John A. Kairalla, Joanne M. Hilden, Zoann E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Y. Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael Borowitz, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Efficacy And Safety Of Bempedoic Acid In Patients Not Receiving Statins In Phase 3 Clinical Trials, Ulrich Laufs, Christie M Ballantyne, Maciej Banach, Harold Bays, Alberico L Catapano, P Barton Duell, Anne C Goldberg, Antonio M Gotto, Lawrence A Leiter, Kausik K Ray, Leanne T Bloedon, Diane Macdougall, Yang Zhang, G B John Mancini

2020-Current year OA Pubs

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse.

OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins.

METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for …

A Systematic Review Of Patient-Reported Outcome Measures Patients With Chronic Limb-Threatening Ischemia, Philip Goodney, Samir Shah, Yiyuan David Hu, Bjoern Suckow, Scott Kinlay, David G Armstrong, Patrick Geraghty, Megan Patterson, Matthew Menard, Manesh R Patel, Michael S Conte

2020-Current year OA Pubs

Chronic limb-threatening ischemia (CLTI) causes significant morbidity with profound negative effects on health-related quality of life. As the prevalence of peripheral artery disease and diabetes continue to rise in our aging population, the public health impact of CLTI has escalated. Patient-reported outcome measures (PROMs) have become common and important measures for clinical evaluation in both clinical care and research. PROMs are important for the measurement of clinical effectiveness and cost effectiveness and for shared decision-making on treatment options. However, the PROMs used to describe the experience of patients with CLTI are heterogeneous, incomplete, and lack specific applicability to the underlying …

Outcomes Of Ahmed Glaucoma Valve And Transscleral Cyclophotocoagulation In Neovascular Glaucoma, Wesam S Shalaby, Allen Y Ganjei, Brian Wogu, Jonathan S Myers, Marlene R Moster, Reza Razeghinejad, Daniel Lee, Natasha N Kolomeyer, Tarek E Eid, L Jay Katz, Aakriti Garg Shukla

Wills Eye Hospital Papers

Purpose: To determine the outcomes of Ahmed glaucoma valve (AGV) and transscleral diode cyclophotocoagulation (CPC) in neovascular glaucoma (NVG).

Methods: This was a single-center retrospective comparative case series involving chart review of consecutive patients who underwent AGV or CPC for treatment of NVG and had ≥6 months of follow-up. Surgical failure at 6 months, defined as an IOP of >21 or <6 mm Hg with hypotony maculopathy after 1 month, progression to no light perception (NLP) vision, glaucoma reoperation, or removal of AGV were the main outcome measures.

Results: In total, 121 eyes of 121 patients were included (70 AGV and 51 CPC). Baseline demographics, visual acuity (VA), and intraocular pressure (IOP) were comparable between groups. At 6 months, failure was significantly higher in the CPC group …

The Classification Of Scoliosis Braces Developed By Sosort With Srs, Ispo, And Posna And Approved By Esprm., Stefano Negrini, Angelo Gabriele Aulisa, Pavel Cerny, Jean Claude De Mauroy, Jeb Mcaviney, Andrew Mills, Sabrina Donzelli, Theodoros B. Grivas, M Timothy Hresko, Tomasz Kotwicki, Hubert Labelle, Louise Marcotte, Martin Matthews, Joe O'Brien, Eric C. Parent, Nigel Price, Rigo Manuel, Luke Stikeleather, Michael G. Vitale, Man Sang Wong, Grant Wood, James Wynne, Fabio Zaina, Marco Brayda Bruno, Suncica Bulat Würsching, Yilgor Caglar, Patrick Cahill, Eugenio Dema, Patrick Knott, Andrea Lebel, Grigorii Lein, Peter O. Newton, Brian G. Smith

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Studies have shown that bracing is an effective treatment for patients with idiopathic scoliosis. According to the current classification, almost all braces fall in the thoracolumbosacral orthosis (TLSO) category. Consequently, the generalization of scientific results is either impossible or misleading. This study aims to produce a classification of the brace types.

METHODS: Four scientific societies (SOSORT, SRS, ISPO, and POSNA) invited all their members to be part of the study. Six level 1 experts developed the initial classifications. At a consensus meeting with 26 other experts and societies' officials, thematic analysis and general discussion allowed to define the classification …

Identification Of An Optimal Dose Of Intravenous Ketamine For Late-Life Treatment-Resistant Depression: A Bayesian Adaptive Randomization Trial, Marijn Lijffijt, Nicholas Murphy, Sidra Iqbal, Charles E Green, Tabish Iqbal, Lee C Chang, Colin N Haile, Lorna C Hirsch, Nithya Ramakrishnan, Dylan A Fall, Alan C Swann, Rayan K Al Jurdi, Sanjay J Mathew

Faculty, Staff and Students Publications

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Akash Mukherjee, Denái R Milton, Elias J Jabbour, Alison M Gulbis, Tapan Kadia, Nitin Jain, Celina Ledesma, Jan Burger, Alessandra Ferrajoli, William Wierda, L Jeffrey Medeiros, Hagop Kantarjian, Richard Champlin, Issa F Khouri

Faculty, Staff and Student Publications

We aimed to study the risks of graft-versus-host disease (GVHD), non-relapse mortality (NRM) and survival outcomes of allogeneic stem cell transplantation (alloSCT) in patients with chronic lymphocytic leukemia (n = 17), Richter's syndrome (n = 14), or lymphoma (n = 18) after small molecule inhibitors (SMIs). Patients had a median of 4 prior therapies, including ibrutinib (n = 46; 94%), venetoclax (n = 19; 39%), and idelalisib (n = 6; 12%). Twenty-one (43%) had >1 SMI. P53 mutation was detected in 58% of patients. The 3-year overall and progression-free survival rates were 68% and …

Comparative Costs Of Management Strategies For Neonates With Symptomatic Tetralogy Of Fallot, Michael L O'Byrne, Andrew C Glatz, Yuan-Shung V Huang, Michael S Kelleman, Christopher J Petit, Athar M Qureshi, Shabana Shahanavaz, George T Nicholson, Shawn Batlivala, Jeffery J Meadows, Jeffrey D Zampi, Mark A Law, Jennifer C Romano, Christopher E Mascio, Paul J Chai, Shiraz Maskatia, Ivor B Asztalos, Asaad Beshish, Joelle Pettus, Amy L Pajk, Steven J Healan, Lindsay F Eilers, Taylor Merritt, Courtney E Mccracken, Bryan H Goldstein

Faculty, Staff and Students Publications

BACKGROUND: Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity.

OBJECTIVES: This study sought to compare the economic costs associated with PR and SR in neonates with sTOF.

METHODS: Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and …

Paradoxical Effects Of Osteoprotegerin On Vascular Function: Inhibiting Inflammation While Promoting Oxidative Stress?, Nhat-Tu Le, Elizabeth A Olmsted-Davis, Jun-Ichi Abe

Faculty, Staff and Student Publications

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor or tumor necrosis factor receptor superfamily member 11B, is well known as a modulator of bone remodeling. The contribution of OPG to cardiovascular disease (CVD) has been suggested, but its molecular mechanism is complex and remains unclear. In the present study, Alves-Lopes et al. (Clin. Sci. (Lond.) (2021) 135(20): https://doi.org/10.1042/CS20210643) reported the critical role of syndecan-1 (SDC-1, also known as CD138), a surface protein part of the endothelial glycocalyx, in OPG-induced vascular dysfunction. The authors found that in endothelial cells (ECs), through SDC-1, OPG increased eNOS Thr495 phosphorylation, thereby inhibiting eNOS activity. …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Judith Trotman, Paula Marlton, Javier Munoz, Patrick Johnston, David Simpson, Jennifer C Stern, Radha Prathikanti, Kenneth Wu, William Novotny, Jane Huang, Constantine S Tam

Faculty, Staff and Student Publications

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response …

Effect Of Domperidone Therapy On Gastroparesis Symptoms: Results Of A Dynamic Cohort Study By Niddk Gastroparesis Consortium, Irene Sarosiek, Mark Van Natta, Henry P Parkman, Thomas Abell, Kenneth L Koch, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A Hamilton, Pankaj J Pasricha, Katherine P Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W Mccallum

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).

METHODS: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. …