Medicine and Health Sciences Commons^™

Intervention For Cognitive Reserve Enhancement In Delaying The Onset Of Alzheimer's Symptomatic Expression (Increase), A Randomized Controlled Trial: Rationale, Study Design, And Protocol, Daniela C. Moga, Brooke F. Beech, Erin L. Abner, Frederick A. Schmitt, Riham H. El Khouli, Ashley I. Martinez, Lynne Eckmann, Mark Huffmyer, Rosmy George, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Case 22-2019: A 65-Year-Old Woman With Myopathy., Marinos C. Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Development Of A Non-Invasive Device For Swallow Screening In Patients At Risk Of Oropharyngeal Dysphagia: Results From A Prospective Exploratory Study, Catriona M. Steele, Rajat Mukherjee, Juha M. Kortelainen, Harri Pölönen, Michael Jedwab, Susan L. Brady, Kayla Brinkman Theimer, Susan Langmore, Luis F. Riquelme, Nancy B. Swigert, Philip M. Bath, Larry B. Goldstein, Richard L. Hughes, Dana Leifer, Kennedy R. Lees, Atte Meretoja, Natalia Muehlemann

Neurology Faculty Publications

Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, …

The Effects Of Long-Term Benzodiazepine Use And Withdrawal In The Elderly, Lydia Suchecki, Hannah Granger, Jamie Kellner, Mary Ellen Hethcox

Pharmacy and Wellness Review

Benzodiazepines remain a commonly prescribed medication in the United States, and the high usage of this drug class is especially a concern in the elderly population for several reasons. First, elderly patients metabolize drugs differently, leading to varying responses. Age-related changes also have a significant impact on the effects of benzodiazepines. Second, elderly patients are more likely to be taking multiple centrally-acting drugs, which can further exacerbate negative effects. In regard to long-term benzodiazepine use, elderly patients experience an increased risk of cognitive impairment, motor vehicle accidents, decline in physical performance, falls and subsequent fractures, and sleep disturbances. Withdrawal is …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …

Flecainide Toxicity Resulting In Pacemaker Latency And Intermittent Failure To Capture, John M. Suffredini, Joshua Rutland, Peter Akpunonu, Regan Baum, John Catanzaro, Claude S. Elayi

Emergency Medicine Faculty Publications

BACKGROUND Flecainide is a class Ic antiarrhythmic agent used in the treatment of supraventricular and ventricular arrhythmias. It is associated with a potent adverse effect profile; however, the effects of flecainide toxicity in the setting of a pacemaker have not been well described. We describe a unique case of flecainide toxicity secondary to acute kidney injury in the setting of a dual-chamber pacemaker, resulting in ventricular capture latency and intermittent failure to capture.

CASE REPORT The patient was a 91-year-old female with a history of atrial fibrillation maintained in sinus rhythm on flecainide, who presented complaining of purple visual disturbances …

Neurological Improvement Of Perineural And Leptomeningeal Spread Of Squamous Cell Carcinoma Treated With Intrathecal Chemotherapy And Systemic Egfr Inhibition., Vincent Alexander Van Vugt, Marlon Garzo Saria, Andres Javier, Navin Kesari, Tiffany Turpin, Santosh Kesari

Marlon Garzo Saria, PhD, RN, AOCNS, FAAN

Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy.

The Significance Of So-Called Equivocal Immunohistochemical Staining For Cytomegalovirus In Colorectal Biopsies, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Journal Articles

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, …

Report Of The First Patient Treated For Pelvic Sarcoma With A Directional 103pd Brachytherapy Device., Serguei A. Castaneda, Marian Khalili, Jacqueline Emrich, Veronica M Zoghbi, Michael S Weingarten, Mark J Rivard, Wilbur B Bowne, Jaganmohan Poli

Department of Radiation Oncology Faculty Papers

No abstract provided.

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

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 …

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 …

The Relationship Of Creatinine, Sodium, Hematocrit And Hemoglobin A1c To 30-Day Hospital Readmission Among Older Adults With Type 2 Diabetes, Shmilah Choudhary, Meet Shah, Sanath Shetty, Terri Ginsberg, Matthew H. Mclaughlin

Rowan-Virtua Research Day

Introduction:Reducing thirty-day hospital readmissions is a top healthcare priority. However, there is little research describing the risk factors of readmission among patients with diabetes, especially for older adults. Understanding what the risk factors are for 30-day hospital readmission for older adults with type 2 diabetes would help identify patients at risk of rehospitalization.

Objective:The aim of this study was to identify factors associated with 30-day unplanned hospital readmissions among older adults with T2DM. Factors to be investigated are: patient demographics and three admission laboratory values.

Methods:Participants were older adult s>65 years old with T2DM, admitted to a community hospital …

The Relationship Of Cardiovascular Disease To 30-Day Hospital Readmission Among Older Adults With Type 2 Diabetes Mellitus, Meet Shah, Shmilah Choudhary, Sanath Shetty, Terrie Ginsberg D.O., Matthew H. Mclaughlin

Rowan-Virtua Research Day

Reducing thirty-day hospital readmissions is a top healthcare priority. However, there is little research describing the risk factors of readmission among patients with diabetes, especially for older adults. Understanding what the risk factors are for 30-day hospital readmission for older adults with type 2 diabetes (T2DM) would help identify patients at risk of rehospitalization. The aim of this study was to identify factors associated with 30-day unplanned hospital readmissions among older adults with T2DM.Factors to be investigated are: patient demographics and whether the patient was hospitalized for cardiovascular disease. Participants were older adults>65 years old with T2DM, admitted to …

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 …

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 …

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) …

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 …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

Minimally Invasive Endovascular Repair Of Ascending Thoracic Aortic Aneurysm With Use Of Local Anesthesia And Conscious Sedation, Abdelkader Almanfi, Zvonimir Krajcer

The Texas Heart Institute Journal

Ascending thoracic aortic aneurysm (ATAA) is typically treated surgically. No commercially available device has been specifically designed for endovascular ATAA repair, and currently, multiple anatomic and technical challenges affect its feasibility. Previously, such repairs have been performed with the patients under general anesthesia. We describe a novel, minimally invasive approach to endovascular repair of ATAA, involving local anesthesia, conscious sedation, and 24-hour hospitalization. Two consecutive male patients (ages, 79 and 54 yr) who had comorbidities underwent percutaneous transfemoral endovascular ATAA repair with use of commercially available endografts. Patient 1 had a saccular aneurysm, and Patient 2 had a pseudoaneurysm consequent …

Rationale And Methods For A Multicenter Clinical Trial Assessing Exercise And Intensive Vascular Risk Reduction In Preventing Dementia (Rrad Study), Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller

Neurology Faculty Publications

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of …

Effectiveness Of Artificial Neochordae Implantation In Tricuspid Valve Repair, Salih Salihi, H Tarik Kiziltan, Ahmad Huraibat, Askin Ali Korkmaz, Ibrahim Kara, Mustafa Guden

The Texas Heart Institute Journal

Various techniques for treating tricuspid regurgitation have been described; however, because of scarce data about the long-term outcomes of different repairs, the optimal technique has not been established. We evaluated the effectiveness and durability of artificial neochordae implantation in the treatment of tricuspid regurgitation. From 2009 through 2014, 507 patients underwent tricuspid valve repair at our institution. Of those, 48 patients implanted with artificial neochordae were included in our study. The median age of the participants was 62 years (range, 4-77 yr) and 50% were women. Thirty patients (63%) were in New York Heart Association functional class III, and 11 …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Adam M. Franks, MD

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Adam M. Franks, MD

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …

Effect Of Conditioning Regimen Dose Reduction In Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation., Claudio G. Brunstein, Marcelo C. Pasquini, Soyoung Kim, Mingwei Fei, Kehinde Adekola, Ibrahim A. Ahmed, Mahmoud Aljurf, Vaibhav Agrawal, Jeffrey J. Auletta, Minoo Battiwalla, Nelli Bejanyan, Joseph Bubalo, Jan Cerny, Lynette Chee, Stefan O. Ciurea, Cesar Freytes, Shahinaz M. Gadalla, Robert Peter Gale, Siddhartha Ganguly, Shahrukh K. Hashmi, Peiman Hematti, Gerhard Hildebrandt, Leona A. Holmberg, Oscar B. Lahoud, Heather Landau, Hillard M. Lazarus, Marcos De Lima, Vikram Mathews, Richard Maziarz, Taiga Nishihori, Maxim Norkin, Richard Olsson, Ran Reshef, Seth Rotz, Bipin Savani, Harry C. Schouten, Sachiko Seo, Baldeep M. Wirk, Jean Yared, Shin Mineishi, John Rogosheske, Miguel-Angel Perales

Manuscripts, Articles, Book Chapters and Other Papers

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) …

Heart Failure Symptom Biology In Response To Ventricular Assist Device Implantation., Christopher S Lee, James O Mudd, Karen S Lyons, Quin E Denfeld, Corrine Y Jurgens, Bradley E Aouizerat, Jill M Gelow, Christopher V Chien, Emily Aarons, Kathleen L Grady

Articles, Abstracts, and Reports

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation.

OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF.

METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], …