North Shore LIJ Health System
North Shore LIJ Health System
Smith B.,Feinstein Institute for Medical Research |
Sigal I.R.,Feinstein Institute for Medical Research |
Grande D.A.,Feinstein Institute for Medical Research |
Grande D.A.,North Shore LIJ Health System
Immunologic Research | Year: 2015
The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them “antigen sequestered.” It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins—to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation. © 2015, Springer Science+Business Media New York.
Goldberg A.,North Shore LIJ Health System
Cardiology in Review | Year: 2010
Pulmonary arterial hypertension (PAH) is an entity that is known to complicate connective tissue diseases (CTD). PAH in CTD is a very important diagnosis which greatly affects treatment and prognosis. The most commonly affected CTD is scleroderma, although lupus, inflammatory myopathies such as poly and dermatomyositis, and mixed CTD are also associated with PAH. The manifestations of PAH have both similarities and differences when occurring in the setting of CTD as compared with idiopathic PAH. These differences are most notable in scleroderma. In this section we will discuss the features of PAH as they appear in CTDs, and in particular, scleroderma. The focus of this article is an approach to the diagnosis and treatment of PAH in CTD, and how this setting might differ from idiopathic and other forms of PAH. © 2010 Lippincott Williams & Wilkins, Inc.
Riegel A.C.,North Shore LIJ Health System
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2014
Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of cine CT. ITVs were delineated on PET using the following methods: 15%, 35%, and 42% of maximum activity concentration, standardized uptake value (SUV) of 2.5 g/mL, 15% of mean activity concentration plus background, a linear function of mean SUV, and the VMSBR model. Predicted threshold values from each method were compared to measured optimal threshold values, and resulting volume magnitudes were compared to cine-CT-derived ITV. Correlation between predicted and measured threshold values ranged from slopes of 0.29 for the simplest single-threshold techniques to 0.90 for the VMSBR technique. R2 values ranged from 0.07 for the simplest single-threshold techniques to 0.86 for the VMSBR technique. The VMSBR segmentation technique that included volume, motion, and source-to-background ratio, produced accurate ITVs in patients when compared with cine-CT-derived ITV.
Spyropoulos A.C.,University of Rochester |
McGinn T.,North Shore LIJ Health System |
Khorana A.A.,University of Rochester
Thrombosis and Haemostasis | Year: 2012
Summary Formalised risk assessment models (RAMs) for venous thromboembol-ism (VTE) using weighted and scored variables have only recently been widely incorporated into international antithrombotic guidelines. Scored and weighted VTE RAMs have advantages over a simplified group-specific VTE risk approach, with the potential to allow more tailored strategies for thromboprophylaxis and an improved estimation of the risk/benefit profile for a particular patient. The derivation of VTE RAMs should be based on variables that are a priori defined or identified in a univariate analysis and the predictive capability of each variable should be rigorously assessed for both clinical and statistical significance and internal consistency and completeness. The assessment of the RAM should include the goodness of fit of the model and con-struction of a prognostic index score. Any VTE RAM which has been derived must undergo validation of that model before it can be used in clinical practice. Validation of the model should be performed in a "deliberate" prospective fashion across several diverse clinical sites using pre-defined criteria using basic standards for performing model validation. We discuss the basic concepts in the derivation of recent scored and weighted VTE RAMs in hospitalised surgical and medical patients and cancer outpatients, the mechanisms for accurate external validation of the models, and implications for their use in clinical practice. © Schattauer 2012.
Arad A.,Beth Israel Deaconess Medical Center |
Proulle V.,Beth Israel Deaconess Medical Center |
Furie R.A.,North Shore LIJ Health System |
Furie B.C.,Beth Israel Deaconess Medical Center |
Furie B.,Beth Israel Deaconess Medical Center
Blood | Year: 2011
Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti-β2-glycoprotein-1 (anti-β2-GP1) antibodies. Although anti-β2-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti-β2-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti-β2-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β2-GP1 bound to agarose. The effects of purified anti-β2-GP1 IgG autoantibodies, of anti-β2-GP1- depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti-β2-GP1 IgG autoantibodies, anti- β2-GP1 antibody-depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti-β2-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti-β2-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti- β2-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis. © 2011 by The American Society of Hematology.
Kapinos G.,North Shore LIJ Health System
Acta Neurochirurgica, Supplementum | Year: 2015
The classic idea that arterial narrowing, called vasospasm (VSP), represents the hallmark of secondary injury after subarachnoid hemorrhage, has been challenged. The more complex and pleiotropic pathophysiological repercussions from the irruption of arterial blood into the subarachnoid layers go beyond the ascribed VSP. Putting adjectives in front of this term, such as “symptomatic,” “microdialytic,” or “angiographic” VSP, is misleading. Delayed cerebral ischemia (DCI) is a better term but remains restrictive to severe hypoperfusive injury and neglects oligemia, edema, and metabolic nonischemic injuries. In recognition of these issues, the international conference on VSP integrated “neurovascular events” into its name (www.vasospasm2013.com) and a multidisciplinary research group was formed in 2010 to study subgroups of DCI/VSP and their respective signifi cance. In three parts, this tiered article provides a broader defi nitional envelope for DCI and secondary neurovascular insults after SAH, with a rubric for each subtype of delayed neuronal dysfunction. First, it pinpoints the need for nosologic precision and covers current terminological inconsistency. Then, it highlights the input of neuroimaging and neuromonitoring in defi ning secondary injurious processes. Finally, a new categorization of deteriorating patients is proposed, going beyond a hierarchical or dichotomized defi nition of VSP/DCI, and common data elements are suggested for future trials. © Springer International Publishing Switzerland 2015.
Kwak N.,North Shore LIJ Health System |
Siegel D.,North Shore LIJ Health System
Current Urology Reports | Year: 2014
Varicocele is a common treatable cause of testicular pain, male infertility, and Leydig cell dysfunction. Scrotal ultrasonography has become the modality of choice in the diagnosis and post-treatment follow-up of varicocele. Visualization of dilated veins and reflux into the pampiniform plexus enables accurate diagnosis. Although the pathophysiology of varicocele in testicular dysfunction remains unclear, numerous studies have established significant improvement in the seminal parameters and pregnancy rates after varicocele repair. Interventional therapy is a minimally invasive effective treatment option for primary and salvage varicocele repair. This review discusses sonographic criteria used in the pre- and post-procedural evaluation of varicocele and various interventional techniques for varicocele treatment. © 2014 Springer Science+Business Media.
Kassavin D.S.,North Shore LIJ Health System |
Constantinopoulos G.,Monmouth Medical Center
Journal of Endovascular Therapy | Year: 2012
Purpose: To describe the use of in situ fenestration to facilitate management of a disconnected iliac stent-graft limb that could not be repaired by conventional endovascular techniques. Technique: An 85-year-oldman who had a Zenith endovascular graft deployed 3 years earlier for a 10-cm infrarenal abdominal aortic aneurysm presented with separation of the right iliac stent-graft limb from the main body, resulting in type III endoleak and sac enlargement. The disconnected limb occluded the ostiumof themain stent-graft body, blocking all conventional endovascular techniques to traverse the graft limb-main body intersection. To overcome the problem, the cephalad portion of the proximal disconnected limb overlying the main body gate was successfully fenestrated with an endoscopic FNA needle and continuity restored with a Viabahn stent-graft across the balloon-modeled fenestration. Conclusion: In situ fenestration of endovascular stent-grafts may be a useful adjunct in performing rescues of late complications in patients not suitable for open repair. © 2012 by the International Society of Endovascular Specialists.
Mosak J.,North Shore LIJ Health System |
Furie R.,North Shore LIJ Health System
Lupus | Year: 2013
B lymphocyte stimulator (BLyS), a protein discovered in the 1990s that induces B cell proliferation and differentiation, promotes B cell survival, and is important in immunoglobulin class switching, was the target of a drug development program launched by Human Genome Sciences in the early part of the last decade. Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy. This program, whose studies spanned approximately 10 years from phase I through phase III, was founded on sound biology and advanced on logic and perseverance.Pre-clinical experimentation in murine models of SLE as well as observational studies in human SLE provided sufficient evidence to support the use of an inhibitor of BLyS as a novel therapy to reduce SLE disease activity. Progressing from phase I through a robust phase III program was no easy task given the complexities of SLE trial design. These challenges were overcome with the implementation of strict study entry requirements, the development of a novel responder index, and rigorous rules regarding background therapies. The success of two phase III studies and the approval of belimumab by the US Food and Drug Administration represent an unprecedented milestone in the history of SLE drug development. Belimumab was the first drug approved in SLE in over 50 years and was the first drug ever approved in SLE through the conventional route of randomized controlled trials. This article reviews the biology of BLyS, clinical trial results, and some of the emerging data from the robust phase II and III datasets. © The Author(s), 2013. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav.
Schwartz D.L.,North Shore LIJ Health System
Current Oncology Reports | Year: 2012
Head and neck intensity-modulated radiotherapy (IMRT) remains toxic, and cannot compensate for anatomic changes or tumor response that occur during treatment. Adaptive radiotherapy (ART) is a novel approach to correct for variations in geometry of tumor and bystander anatomy with repeated imaging-based modification of treatment delivery. Technical limitations have hampered introduction of ART into routine practice. This review summarizes investigationalchallenges impacting development of head and neck ART, describes findings from early clinical testing of an automated ART platform, and highlights emerging directions of ongoing research. © 2012 Springer Science+Business Media, LLC.