Medicine and Health Sciences Commons^™

Controversies About Lyme Disease-Reply, Eugene D. Shapiro, Gary P. Wormser

NYMC Faculty Publications

No abstract provided.

Clinical Trials Of Car-T Cells In China, B Liu, Y Song, Delong Liu

NYMC Faculty Publications

Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications. Multi-target CAR-engineered T cells are also entering clinical trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new frontiers in CAR-T cell development. In this study, we analyzed the characteristics …

Sleeper Cells: The Stringent Response And Persistence In The Borreliella (Borrelia) Burgdorferi Enzootic Cycle, Felipe C. Cabello, Henry Godfrey, J Bugrysheva, Stuart A. Newman

NYMC Faculty Publications

Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B. burgdorferi. It modulates the expression of identified and unidentified open reading frames needed to deal with and overcome the many …

Incidence, Risks, And Types Of Infections In Pediatric Long-Term Care Facilities, Lisa Saiman, Philip Maykowski, Meghan Murray, Bevin Cohen, Natalie Neu, Gordon R. Hutcheon, Elaine Larson

NYMC Faculty Publications

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects.

Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs).

Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from …

Metabolic Differentiation Of Early Lyme Disease From Southern Tick-Associated Rash Illness (Stari), C Molins, L Ashton, Gary Wormser, B Andre, A Hess, J Belisle

NYMC Faculty Publications

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early …

Neuropsychiatric Aspects Of Infectious Diseases: An Update, Sahil Munjal, Stephen J. Ferrando, Zachary Freyberg

NYMC Faculty Publications

Among the critically ill, infectious diseases can play a significant role in the etiology of neuropsychiatric disturbances. All critical care physicians are familiar with delirium as a secondary complication of systemic infection. This article focuses on key infectious diseases that commonly and directly produce neuropsychiatric symptoms, including direct infection of the central nervous system, human immunodeficiency virus infection, and AIDS.

Macrolides Selectively Inhibit Mutant Kcnj5 Potassium Channels That Cause Aldosterone-Producing Adenoma, Ute Scholl, Laura Abriola, Chengbiao Zhang, Esther Reimer, Mark Plummer, Wenhui Wang, Richard Lifton

NYMC Faculty Publications

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of …

Ketamine Use For Successful Resolution Of Post-Ercp Acute Pancreatitis Abdominal Pain, S Agerwala, D Sundarapandiyan, Garret Weber

NYMC Faculty Publications

We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute …

Gvhd After Umbilical Cord Blood Transplantation For Acute Leukemia: An Analysis Of Risk Factors And Effect On Outcomes, Y Chen, T Wang, Michael T. Hemmer, A Alousi, J Pidala, Mitchell Cairo, C Cutler

NYMC Faculty Publications

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord bloodtransplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acuteGvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and …

Childhood Obesity: The Role Of The Mental Health Professional, Barry Panzer

NYMC Faculty Publications

This work consists of two major components: understanding the nature of childhood obesity and providing clinical services. Factors responsible for the current epidemic will be outlined, as will the current definition of the disorder. Statistical data regarding the epidemiology of weight disorders in childhood will be provided in order to give a perspective of the problem. Various obesity trajectories and their differential diagnostic and treatment issues will be thoroughly explored. The intervention section intends to help clinicians to evaluate salient factors in assessing the obese child and to identify appropriate goals and treatment methods. The course will provide vital information …

Respiratory Syncytial Virus Hospitalization Risk In The Second Year Of Life By Specific Congenital Heart Disease Diagnoses, Deborah Friedman, J Fryzek, X Jiang, A Bloomfield, C Ambrose, P Wong

NYMC Faculty Publications

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age …

Double Balloon Cervical Ripening Catheter For Control Of Massive Hemorrhage In A Cervical Ectopic Pregnancy, N Zambrano, J Reilly, M Moretti, Nisha Lakhi

NYMC Faculty Publications

Cervical pregnancy can be complicated by perfuse vaginal bleeding. Mechanical compression directed at tamponing the cervical vessels can control hemostasis. There are several types of balloon catheters that have been described for cervical compression. However use of a double balloon catheter is a novel approach for cervical tamponade, as one balloon is positioned below the external cervical os and the second balloon is situated above in the internal cervical os. This compresses the cervix from internal os to external os between the two balloons, forming a "cervical sandwich." We describe this method of cervical tamponade using a silicone double balloon …

Characteristics Of Hiv-Infected Children At Enrollment Into Care And At Antiretroviral Therapy Initiation In Central Africa, A Adedimeji, A Edmonds, Donald R. Hoover, Qiuhu Shi, J Sinayobye, M Nduwimana, P Lelo, D Nash, K Anastos, M Yotebieng

NYMC Faculty Publications

BACKGROUND: Despite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described. MATERIALS AND METHODS: Data are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0-15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and …

Global, Regional, And National Incidence, Prevalence, And Years Lived With Disability For 310 Diseases And Injuries, 1990-2015: A Systematic Analysis For The Global Burden Of Disease Study 2015, T Vos, C Allen, M Arora, R Barber, Z Bhutta, A Brown, A Carter, D Casey, Sahil Khera, M Tavakkoli, Gbd 2015 Disease And Injury Incidence And Prevalence Collaborators

NYMC Faculty Publications

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with …

Global, Regional, And National Life Expectancy, All-Cause Mortality, And Cause-Specific Mortality For 249 Causes Of Death, 1980-2015: A Systematic Analysis For The Global Burden Of Disease Study 2015, H Wang, M Naghavi, M Coggeshall, L Dandona, D Dicker, Sahil Khera, M Tavakkoli, Gbd 2015 Mortality And Causes Of Death Collaborators

NYMC Faculty Publications

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child …

Longer-Term Therapy For Symptoms Attributed To Lyme Disease, Gary P. Wormser

NYMC Faculty Publications

Comment on

• Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. [N Engl J Med. 2016]

Antimicrobials: A Global Alliance For Optimizing Their Rational Use In Intra-Abdominal Infections (Agora), M Sartelli, D Weber, E Ruppe, M Bassetti, B Wright, L Ansaloni, F Catena, F Coccolini, Rifat Latifi, T Zakrison, A Corcione, R Melotti, C Viscoli, P Viale

NYMC Faculty Publications

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in …

Coronary-Artery Bypass Surgery In Patients With Ischemic Cardiomyopathy, Eric J. Velazquez, Julio A. Panza, Torsten Doenst, Patrice Desvigne-Nickens, George Sopko, Stiches Investigators

NYMC Faculty Publications

BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear.

METHODS: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death …

Clinical Factors Associated With Long-Term Complete Remission Versus Poor Response To Chemotherapy In Hiv-Infected Children And Adolescents With Kaposi Sarcoma Receiving Bleomycin And Vincristine: A Retrospective Observational Study, Nader K. El-Mallawany, William Kamiyango, Jeremy Kim Slone, Jimmy Villiera, Carrie L. Kovarik, Carrie M. Cox, Dirk Dittmer, Saeed Ahmed, Gordon E. Schutze, Michael E. Scheurer, Peter N. Kazembe, Parth S. Mehta

NYMC Faculty Publications

Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7-17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral …

Managing Agitation Associated With Schizophrenia And Bipolar Disorder In The Emergency Setting, Scott Zeller, Leslie Citrome

NYMC Faculty Publications

INTRODUCTION: Patient agitation represents a significant challenge in the emergency department (ED), a setting in which medical staff are working under pressure dealing with a diverse range of medical emergencies. The potential for escalation into aggressive behavior, putting patients, staff, and others at risk, makes it imperative to address agitated behavior rapidly and efficiently. Time constraints and limited access to specialist psychiatric support have in the past led to the strategy of "restrain and sedate," which was believed to represent the optimal approach; however, it is increasingly recognized that more patient-centered approaches result in improved outcomes. The objective of this …

Retrospective Studies In Lower Urinary Tract Dysfunction Do Matter, Israel Franco

NYMC Faculty Publications

Comment on Clinical course of a cohort of children with non-neurogenic daytime urinary incontinence symptoms followed at a tertiary center. [J Pediatr (Rio J). 2016]

Post-Prandial Glucose And Insulin Responses Of Hummus Alone Or Combined With A Carbohydrate Food: A Dose-Response Study, Livia S. Augustin, Laura Chiavaroli, Janice Campbell, Adish Ezatagha, Alexandra L. Jenkins, Amin Esfahani, Cyril Kendall

NYMC Faculty Publications

OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested.

METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited …

Hypoacetylation, Hypomethylation, And Dephosphorylation Of H2b Histones And Excessive Histone Deacetylase Activity In Du-145 Prostate Cancer Cells, Shundong Cang, Xiaobin Xu, Yuehua Ma, Delong Liu, Jenwei Chiao

NYMC Faculty Publications

BACKGROUND: Hypoacetylation on histone H3 of human prostate cancer cells has been described. Little is known about the modifications of other histones from prostate cancer cells.

METHODS: Histones were isolated from the prostate cancer cell line DU-145 and the non-malignant prostatic cell line RC170N/h. Post-translational modifications of histone H2B were determined by liquid chromatography-mass spectrometry (LC-MS)/MS.

RESULTS: The histone H2B of the prostate cancer cell line DU-145 was found to have hypoacetylation, hypomethylation, and dephosphorylation as compared to the non-malignant prostatic cell line RC170N/h. H2B regained acetylation on multiple lysine residues, phosphorylation on Thr19, and methylation on Lys23 and Lys43 …

Atp-Site Binding Inhibitor Effectively Targets Mtorc1 And Mtorc2 Complexes In Glioblastoma, Jayson Neil, Craig Shannon, Avinash Mohan, Dimitri Laurent, Raj Murali, Meena Jhanwar-Uniyal

NYMC Faculty Publications

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding …

How Clinicians Feel About Working With Spouses Of The Chronically Ill, Douglas Ingram

NYMC Faculty Publications

Clinicians who provide psychotherapy to spouses or partners of the chronically ill were solicited through listserves of psychodynamic and other organizations. The current report excluded those therapists working with spouses of dementia patients. Interviews were conducted with clinicians who responded. The interviews highlight the challenges commonly encountered by psychotherapeutic work with this cohort of therapy patients. A comparison is drawn that shows both overlap and distinctions between the experiences of those therapists engaging with spouses of chronically ill patients without a dementing process and those working with spouses of chronically ill patients who do suffer from a dementing process.

Change In Overactive Bladder Symptoms After Surgery For Stress Urinary Incontinence In Women, Halina Zyczynski, Michael E Albo, Howard B Goldman, Clifford Y Wai, Larry T Sirls, Linda Brubaker, Peggy Norton, R E Varner, Maude Carmel, Hae-Young Kim

NYMC Faculty Publications

OBJECTIVE: To assess change in overactive bladder (OAB) symptoms up to 5 years after surgery and to identify associated predictors of change from baseline.

METHODS: This is a secondary analysis of data from three multicenter urinary incontinence (UI) surgical trials of women with stress-predominant mixed UI assigned to Burch colposuspension, autologous fascial sling, or retropubic or transobturator midurethral slings. The primary outcome was improvement of 70% or greater from baseline in symptoms measured by the Urinary Distress Inventory-Irritative subscale. Surgical groups were compared within respective trials. Generalized linear models were fit using 1-year and up to 5-year data.

RESULTS: Significant …

Beta-Blocker Use And 30-Day All-Cause Readmission In Medicare Beneficiaries With Systolic Heart Failure, Vikas Bhatia, Kumar Sanam, Taimoor Hashim, Prakash Deedwania, Wilbert S. Aronow, Ross Fletcher, Ali Ahmed

NYMC Faculty Publications

BACKGROUND: Beta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act.

METHODS: Of the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction

RESULTS: Beta-blocker use was not associated with 30-day all-cause readmission (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.64-1.18) or heart failure readmission (HR 0.95; 95% CI, 0.57-1.58), but was significantly associated with lower …

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

A Device For Performing Automated Balloon Catheter Inflation Ischemia Studies, Silas Leavesley, Whitley Ledkins, Petra Rocic

NYMC Faculty Publications

Coronary collateral growth (arteriogenesis) is a physiological adaptive response to transient and repetitive occlusion of major coronary arteries in which small arterioles (native collaterals) with minimal to no blood flow remodel into larger conduit arteries capable of supplying adequate perfusion to tissue distal to the site of occlusion. The ability to reliably and reproducibly mimic transient, repetitive coronary artery occlusion (ischemia) in animal models is critical to the development of therapies to restore coronary collateral development in type II diabetes and the metabolic syndrome. Current animal models for repetitive coronary artery occlusion implement a pneumatic occluder (balloon) that is secured …