Breast Cancer And Aging: Results Of The U13 Conference Breast Cancer Panel,
2014
Northwell Health
Breast Cancer And Aging: Results Of The U13 Conference Breast Cancer Panel, M. F. Barginear, H. Muss, G. Kimmick, C. Owusu, E. Mrozek, A. Shahrokni, K. Ballman, A. Hurria
Journal Articles
Breast cancer is predominantly a disease of older women, yet there is a knowledge gap due to the persisting misalignment between the age distribution of women with breast cancer and the age distribution of participants in clinical trials. The purpose of this report is to state the U13 conference breast cancer panel's recommendations regarding therapeutic clinical trials that will fill gaps in knowledge regarding the care of older patients with breast cancer. The U13 conference was a collaboration between the Cancer and Aging Research Group and the National Institute on Aging and the National Cancer Institute (NCI). Clinical trials should …
C1q-Mediated Repression Of Human Monocytes Is Regulated By Lair-1,
2014
Northwell Health
C1q-Mediated Repression Of Human Monocytes Is Regulated By Lair-1, M. Son, B. Diamond
Journal Articles
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal function of both the innate and the adaptive immune system, leading to a loss of tolerance to self-antigens. Monocytes are a key component of the innate immune system and are efficient producers of multiple cytokines. In SLE, inappropriate activation of monocytes is thought to contribute to the loss of self-tolerance. In this study, we demonstrate that type 1 interferon (IFN) production by CpG-challenged monocytes can be suppressed by C1q through activate leukocyte-associated Ig-like receptor-1 (LAIR-1), which contains ITIM motifs. The phosphorylation of LAIR-1 and the interaction of LAIR-1 …
Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin,
2014
Northwell Health
Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee
Journal Articles
Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-kappa B, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-kappa B conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-kappa B played …
Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion,
2014
Northwell Health
Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion, S. Haque, X. J. Yan, L. Rosen, S. Mccormick, N. Chiorazzi, P. K. A. Mongini
Journal Articles
Within T-cell-dependent germinal centers, p53 gene transcription is repressed by Bcl-6 and is thus less vulnerable to mutation. Malignant lymphomas within inflamed extranodal sites exhibit a relatively high incidence of p53 mutations. The latter might originate from normal B-cell clones manifesting activation-induced cytosine deaminase (AID) and up-regulated p53 following T-cell-independent (TI) stimulation. We here examine p53 gene transcription in such TI clones, with a focus on modulatory effects of prostaglandin E-2 (PGE(2)), and evaluate progeny for p53 mutations. Resting IgM(+)IgD(+)CD27(-) B cells from human tonsils were labeled with CFSE and stimulated in vitro with complement-coated antigen surrogate, IL-4, and BAFF …
Endobronchial Ultrasound As A Confirmatory Tool For The Diagnosis Of Pulmonary Embolism,
2014
Northwell Health
Endobronchial Ultrasound As A Confirmatory Tool For The Diagnosis Of Pulmonary Embolism, K. Harris, M. Chalhoub
Journal Articles
No abstract provided.
External Validation Of The Risk Assessment Model Of The International Medical Prevention Registry On Venous Thromboembolism (Improve) For Medical Patients In A Tertiary Health System,
2014
Zucker School of Medicine at Hofstra/Northwell
External Validation Of The Risk Assessment Model Of The International Medical Prevention Registry On Venous Thromboembolism (Improve) For Medical Patients In A Tertiary Health System, D. Rosenberg, A. Eichorn, M. Alarcon, L. Mccullagh, T. Mcginn, A. Spyropoulos
Journal Articles
Background-Hospitalized medical patients are at risk for venous thromboembolism (VTE). Universal application of pharmacological thromboprophylaxis has the potential to place a large number of patients at increased bleeding risk. In this study, we aimed to externally validate the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk assessment model in a hospitalized general medical population. Methods and Results-We identified medical discharges that met the IMPROVE protocol. Cases were defined as hospital-acquired VTE and confirmed by diagnostic study within 90 days of index hospitalization; matched controls were also identified. Risk factors for VTE were based on the IMPROVE risk assessment …
The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice,
2014
Zucker School of Medicine at Hofstra/Northwell
The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors
Journal Articles
Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to …
Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response,
2014
Northwell Health
Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond
Journal Articles
A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in …
Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice,
2014
Northwell Health
Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson
Journal Articles
Objective. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods. Kidneys from (NZB x NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self-organizing maps were performed. Results. Few changes in …
Impact On House Staff Evaluation Scores When Changing From A Dreyfus- To A Milestone-Based Evaluation Model: One Internal Medicine Residency Program's Findings,
2014
Zucker School of Medicine at Hofstra/Northwell
Impact On House Staff Evaluation Scores When Changing From A Dreyfus- To A Milestone-Based Evaluation Model: One Internal Medicine Residency Program's Findings, K. A. Friedman, S. Balwan, F. Cacace, K. Katona, S. Sunday, S. Chaudhry
Journal Articles
Purpose: As graduate medical education (GME) moves into the Next Accreditation System (NAS), programs must take a critical look at their current models of evaluation and assess how well they align with reporting outcomes. Our objective was to assess the impact on house staff evaluation scores when transitioning from a Dreyfus-based model of evaluation to a Milestone-based model of evaluation. Milestones are a key component of the NAS. Method: We analyzed all end of rotation evaluations of house staff completed by faculty for academic years 2010-2011 (pre-Dreyfus model) and 2011-2012 (post-Milestone model) in one large university-based internal medicine residency training …
Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models,
2014
Northwell Health
Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed
Journal Articles
Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …
Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools,
2014
Northwell Health
Measures Of User Experience In A Streptococcal Pharyngitis And Pneumonia Clinical Decision Support Tools, D. Mann, M. Knaus, L. Mccullagh, A. Sofianou, L. Rosen, T. Mcginn, J. Kannry
Journal Articles
Objective: To understand clinician adoption of CDS tools as this may provide important insights for the implementation and dissemination of future CDS tools. Materials and Methods: Clinicians (n=168) at a large academic center were randomized into intervention and control arms to assess the impact of strep and pneumonia CDS tools. Intervention arm data were analyzed to examine provider adoption and clinical workflow. Electronic health record data were collected on trigger location, the use of each component and whether an antibiotic, other medication or test was ordered. Frequencies were tabulated and regression analyses were used to determine the association of tool …
Mif: Mood Improving/Inhibiting Factor?,
2014
Zucker School of Medicine at Hofstra/Northwell
Mif: Mood Improving/Inhibiting Factor?, J. Bloom, Y. Al-Abed
Journal Articles
Although major depressive disorder imposes a serious public health burden and affects nearly one in six individuals in developed countries over their lifetimes, there is still no consensus on its pathophysiology. Inflammation and cytokines have emerged as a promising new avenue in depression research, and, in particular, macrophage migration inhibitory factor (MIF) has been shown to be significant in depression physiology. In this review we summarize current research on MIF and depression. We highlight the arguments for MIF as a pro-and antidepressant species and discuss the potential implications for therapeutics.
A Multicenter Population-Based Effectiveness Study Of Teleintensive Care Unit-Directed Ventilator Rounds Demonstrating Improved Adherence To A Protective Lung Strategy, Decreased Ventilator Duration, And Decreased Intensive Care Unit Mortality, T. Kalb, J. Raikhelkar, S. Meyer, F. Ntimba, J. Thuli, M. J. Gorman, I. Kopec, C. Scurlock
Journal Articles
Purpose of the study: The purpose of the study is to determine if teleintensive care unit (ICU)-directed daily ventilator rounds improved adherence to lung protective ventilation (LPV), reduced ventilator duration ratio (VDR), and ICU mortality ratios. Method used: A retrospective observational longitudinal quarterly analysis of adherence to low tidal volume LPV (< 7.5 mL/kg predicted body weight; PaO2/fraction of inspired oxygen < 300), ventilator duration, and ICU mortality ratios (Acute Physiology and Chronic Health Evaluation IV-adjusted). The teleICU practice used Philips (Andover, MA) VISICU eCareManager (TM) (Andover, MA) platform, providing ICU care and process improvement. Results: Before ventilator rounds implementation, there was wide variation in hospital adherence to low tidal volume (29.5 +/- 18.2; range 10%-69%). Longitudinal improvement was seen across hospitals in the 3 Qs after implementation, reaching statistical significance by Q3 postimplementation (44.9 +/- 15.7; P < .002 by 2-tailed Fisher exact test), maintained at 2 subsequent Qs (48% and 52%; P < .001). Ventilator duration ratio also showed preimplementation variability (1.08 +/- .34; range 0.71-1.90). After implementation, absolute and significant mean VDR reduction was observed (0.92 +/- .28; -15.8%, P < .05). Intensive care unit mortality ratio demonstrated longitudinal improvement, reaching significance after the Q3 postimplementation (0.94 vs 0.67; P < .04), and this was sustained in the most recent Q analyzed (0.65; P < .03). Conclusions: Implementation of teleICU-directed ventilator rounds was associated with improved and durable adherence to LPV and significant reductions in both VDR and ICU mortality. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3ol).
Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice,
2014
Northwell Health
Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu
Journal Articles
Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-kappa B-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-kappa B mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-kappa B pathway activated the activator protein (AP)-1 pathway (NF-kappa B-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-kappa B. The NF-kappa B-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) …
A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production,
2014
Northwell Health
A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein
Journal Articles
Immune suppression by regulatory T cells and regulatory B cells is a critical mechanism to limit excess inflammation and autoimmunity. IL-10 is considered the major mediator of B cell induced immune suppression. We report a novel mechanism for immune suppression through adenosine generation by B cells. We identified a novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is not. Approximately 30-50% of B-1 cells (B220(+)CD23(-)) and IL-10 producing B (B10) cells (B220(+)CD5(+)CD1d(hi)) are …
Perforation In A Patient With Stercoral Colitis And Diverticulosis: Who Did It?,
2014
Northwell Health
Perforation In A Patient With Stercoral Colitis And Diverticulosis: Who Did It?, V. R. Bhatt, S. Murukutla, J. Dipoce, S. Gustafson, D. Sarkany, K. Mody, W. D. Widmann, A. Gottesman
Journal Articles
Stercoral colitis with perforation of the colon is an uncommon, yet life-threatening cause of the acute abdomen. No one defining symptom exists for stercoral colitis; it may present asymptomatically or with vague symptoms. Diagnostic delay may result in perforation of the colon resulting in complications, even death. Moreover, stercoral perforation of the colon can also present with localized left lower quadrant abdominal pain masquerading as diverticulitis. Diverticular diseases and stercoral colitis share similar pathophysiology; furthermore, they may coexist, further complicating the diagnostic dilemma. The ability to decide the cause of perforation in a patient with both stercoral colitis and diverticulosis …
Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis,
2014
Northwell Health
Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors
Journal Articles
Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M ( IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early …
A Post-2011 Time Motion Study--The Authors' Reply,
2014
Zucker School of Medicine at Hofstra/Northwell
A Post-2011 Time Motion Study--The Authors' Reply, L. Block, R. Habicht, A. W. Wu, S. V. Desai, K. Wang, K. N. Silva, T. Niessen, N. Oliver, L. Feldman
Journal Articles
No abstract provided.
Rare Case Of Coronary To Pulmonary Vein Fistula With Coronary Steal Phenomenon,
2014
Northwell Health
Rare Case Of Coronary To Pulmonary Vein Fistula With Coronary Steal Phenomenon, E. A. Barsoum, F. B. Saiful, D. Asti, R. Morcus, G. Khoueiry, J. Lafferty, D. A. Mccord
Journal Articles
Coronary artery fistulas are abnormal connections between coronary artery territories and cardiac chambers or major vessels, most of them are congenital. Patients with coronary artery fistula can be asymptomatic or present with different symptoms like angina. Cardiac computed tomography (CT) is one of the best modalities for diagnosis. We present an elderly patient that presented with angina symptoms, non invasive stress test was positive for ischemic heart disease, coronary angiogram could not reveal any obstructive lesions, but an abnormal branch of the left descending coronary artery (LAD), cardiac CT showed fistula that connect left anterior descending coronary artery to left …
