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Gallamini A.,BMT Unit | Kostakoglu L.,Mount Sinai Medical Center
Blood | Year: 2012

Despite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria.Afinal remark on the appropriate use of interim PET is also provided. © 2012 by The American Society of Hematology.


Tomer Y.,Mount Sinai Medical Center | Tomer Y.,James ters Va Medical Center
Annual Review of Pathology: Mechanisms of Disease | Year: 2014

Recent advances in our understanding of genetic-epigenetic interactions have unraveled new mechanisms underlying the etiology of complex autoimmune diseases. Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of the population. The major AITDs include Graves disease (GD) and Hashimoto's thyroiditis (HT); although these diseases contrast clinically, their pathogenesis involves shared immunogenetic mechanisms. Genetic data point to the involvement of both shared and unique genes. Among the shared susceptibility genes, HLA-DRβ1-Arg74 (human leukocyte antigen DR containing an arginine at position β74) confers the strongest risk. Recent genome-wide analyses have revealed new putative candidate genes. Epigenetic modulation is emerging as a major mechanism by which environmental factors interact with AITD susceptibility genes. Dissecting the genetic-epigenetic interactions underlying the pathogenesis of AITD is essential to uncover new therapeutic targets. © 2014 by Annual Reviews. All rights reserved.


Corti R.,University of Zürich | Fuster V.,Mount Sinai Medical Center
European Heart Journal | Year: 2011

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized countries. Despite advances in our understanding of the pathophysiology, pathogenesis, and new treatment modalities, the absence of an adequate non-invasive imaging tool for early detection limits both the prevention and treatment of patients with various degrees and anatomical localizations of atherothrombotic disease. An ideal clinical imaging modality for atherosclerotic vascular disease should be safe, inexpensive, non-invasive or minimally invasive, accurate, and reproducible, and the results should correlate with the extent of atherosclerotic disease and have high predictive values for future clinical events. High-resolution magnetic resonance imaging (MRI) has emerged as the most promising technique for studying atherothrombotic disease in humans in vivo. Most importantly, MRI allows for the characterization of plaque composition, i.e. the discrimination of lipid core, fibrosis, calcification, and intraplaque haemorrhage deposits. Magnetic resonance imaging also allows for the detection of arterial thrombi and in defining thrombus age. Magnetic resonance imaging has been used to monitor plaque progression and regression in several animal models of atherosclerosis and in humans. Emerging MRI techniques capable of imaging biological processes, including inflammation, neovascularization, and mechanical forces, may aid in advancing our understanding of the atherothrombotic disease. Advances in diagnosis do prosper provided they march hand-in-hand with advances in treatment. We stand at the threshold of accurate non-invasive assessment of atherosclerosis. Thus, MRI opens new strategies ranging from screening of high-risk patients for early detection and treatment as well as monitoring of the target lesions for pharmacological intervention. Identification of subclinical atherosclerosis and early treatment initiation has the potential to surpass conventional risk factor assessment and management in terms of overall impact on cardiovascular morbidity and mortality. Such strategy is currently under clinical investigation. © 2011 The Author.


Kostakoglu L.,Mount Sinai Medical Center
Seminars in Nuclear Medicine | Year: 2013

Preoperative systemic therapy with cytotoxic or biologic anticancer regimens has gained significant popularity in the management of breast cancer. Moreover, there is a worldwide paradigm shift toward an individualized approach to identify predictive surrogate markers for stratifying patients into distinct subgroups to improve outcome after neoadjuvant or adjuvant therapy. Although achievement of pathologic complete response constitutes the gold standard for assessing therapeutic efficacy only a minority of patients achieve a pathologic complete response. Imaging has evolved to play a crucial role in monitoring treatment effectiveness, particularly, early during therapy. There is mounting evidence that (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a more superior metabolic imaging modality than anatomic modalities for assessment of the response during or at completion of treatment. Ultimately, the prediction of therapeutic effectiveness or survival or both by FDG-PET imaging could successfully tailor treatment and avoid unnecessary toxicities. This paper provides an overview of current use and the main indications of FDG-PET and integrated PET/computed tomography in response assessment of breast cancer as well as the future directions for the management using non-FDG-based tracers developed against specific targets. © 2013 Elsevier Inc.


Frucht S.J.,Mount Sinai Medical Center
Movement Disorders | Year: 2013

The definition of dystonia has been a subject of much debate and controversy for the last century. In this paper, a practical definition of dystonia for the movement disorders expert is presented, based on a new algorithm. © 2013 Movement Disorder Society.


Tomer Y.,Mount Sinai Medical Center
Thyroid : official journal of the American Thyroid Association | Year: 2010

BACKGROUND: Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, arise due to complex interactions between environmental and genetic factors. There are sound data coming from epidemiological, family, and twin studies demonstrating a strong genetic influence on the development of AITD. In this review we summarize the new findings on the genetic susceptibility to AITD focusing on emerging mechanisms of susceptibility. SUMMARY: Candidate gene analysis, whole-genome linkage screening, genome-wide association studies, and whole-genome sequencing are the major technologies that have advanced this field, leading to the identification of at least seven genes whose variants have been associated with AITD. One of the major ones is the HLA-DR gene locus. Recently, it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide-binding pocket is key to the etiology of both Graves' disease and Hashimoto's thyroiditis. Several other genes have also been shown to confer susceptibility to AITD. These can be classified into two groups: (i) immune regulatory genes (cytotoxic T lymphocyte-associated protein 4, CD40, protein tyrosine phosphatase-22, and CD25) and (ii) thyroid-specific genes (thyroglobulin and thyrotropin receptor genes). The influence of individual genes on the development of AITD when assessed in a population appears to be weaker than would be expected from the data showing strong genetic susceptibility to AITD. Two possible mechanisms explaining this discrepancy are gene-gene interactions and subset effects. CONCLUSIONS: Significant progress has been made in our understanding of the immunogenetic mechanisms leading to thyroid autoimmunity. For the first time we are beginning to unravel these mechanisms at the molecular level. It is hoped that these new data will be translated into novel therapies and prevention strategies in AITD, such as costimulatory blockade.


Shapiro J.S.,Mount Sinai Medical Center
American journal of public health | Year: 2011

Public health relies on data reported by health care partners, and information technology makes such reporting easier than ever. However, data are often structured according to a variety of different terminologies and formats, making data interfaces complex and costly. As one strategy to address these challenges, health information organizations (HIOs) have been established to allow secure, integrated sharing of clinical information among numerous stakeholders, including clinical partners and public health, through health information exchange (HIE). We give detailed descriptions of 11 typical cases in which HIOs can be used for public health purposes. We believe that HIOs, and HIE in general, can improve the efficiency and quality of public health reporting, facilitate public health investigation, improve emergency response, and enable public health to communicate information to the clinical community.


Miller E.,New York University | Bhardwaj N.,New York University | Bhardwaj N.,Mount Sinai Medical Center
Immunological Reviews | Year: 2013

Dendritic cells (DCs) are a diverse subset of innate immune cells that are key regulators of the host response to human immunodeficiency virus-1 (HIV-1) infection. HIV-1 directly and indirectly modulates DC function to hinder the formation of effective antiviral immunity and fuel immune activation. This review focuses upon the differential dysregulation of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) at various stages of HIV-1 infection providing insights into pathogenesis. HIV-1 evades innate immune sensing by mDCs resulting in suboptimal maturation, lending to poor generation of antiviral adaptive responses and contributing to T-regulatory cell (Treg) development. Dependent upon the stage of HIV-1 infection, mDC function is altered in response to Toll-like receptor ligands, which further hinders adaptive immunity and limits feasibility of therapeutic vaccine strategies. pDC interactions with HIV-1 are pleotropic, modulating immune responses on an axis between immunostimulatory and immunosuppressive. pDCs promote immune activation through an altered phenotype of persistent type I interferon secretion and weak antigen presentation capacity. Conversely, HIV-1 stimulates secretion of indolemine 2,3 dioxygenase (IDO) by pDCs resulting in Treg induction. An improved understanding of the roles and underlying mechanisms of DC dysfunction will be valuable to the development of therapeutics to enhance HIV-specific adaptive responses and to dampen immune activation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Iyer K.R.,Mount Sinai Medical Center
JPEN. Journal of parenteral and enteral nutrition | Year: 2014

For patients with short bowel syndrome (SBS), surgery can play an important role in preventing, mitigating, and, in some cases, reversing intestinal failure (IF). During intestinal resection, bowel length should be conserved to the fullest extent possible to avoid dependence on parenteral nutrition (PN). Bowel salvage may be improved by initially preserving tissue of questionable viability and later reevaluating during "second-look" procedures. Once the patient is stabilized, ostomy reversal and recruitment of distal unused bowel should be prioritized whenever feasible. Following progression to IF, surgical management of SBS depends on the symptoms and anatomical characteristics of the individual patient. For carefully selected patients with rapid intestinal transit and dilated bowel, longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) procedures may provide benefit. Outcomes following STEP and LILT are generally similar, and the choice between these procedures may rest on surgeon preference. For patients with rapid intestinal transit in the absence of bowel dilation, segmental reversal of the small bowel may reduce PN requirements. Intestinal transplantation is the standard of care for patients in whom intestinal rehabilitation attempts have failed and who are at risk of life-threatening complications of PN. Because patients awaiting isolated intestine transplant show increased survival compared with patients awaiting combined intestine-liver transplant, early referral of appropriate patients, before the development of advanced liver disease, is critical to enhancing patient outcomes.


Demicco E.G.,Mount Sinai Medical Center
Advances in Anatomic Pathology | Year: 2013

Mesenchymal neoplasia presents numerous challenges to pathologic classification. Histologic features can be deceiving, and traditional immunohistochemical markers of differentiation may be of little use in narrowing the diagnosis. Fortunately, great strides have been made in unraveling the genetic and genomic alterations associated with both sarcomagenesis and benign neoplasia. In turn, these advances have led to an expansion of the available diagnostic toolkit for sarcoma pathology. In order to assist the practicing pathologist in integrating these tools into their repertoire, this article will discuss some of the latest advances in sarcoma diagnosis, including an update on translocation-associated sarcomas, and will review a number of sarcoma-specific immunohistochemical studies developed over the past decade. Some of the potential uses and pitfalls of commonly used tests will be addressed. Finally, the discussion will briefly touch upon the impact that advances in molecular technologies, particularly targeted gene expression analysis, may have on altering the face of diagnostic pathology. Copyright © 2013 by Lippincott Williams & Wilkins.

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