Perelman Center for Advanced Medicine

Philadelphia, PA, United States

Perelman Center for Advanced Medicine

Philadelphia, PA, United States
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Patel S.H.,Sloan Kettering Cancer Center | Rimner A.,Sloan Kettering Cancer Center | Cohen R.B.,Perelman Center for Advanced Medicine
Translational Lung Cancer Research | Year: 2017

Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed. With regards to SCLC, trials exploring to the combination of immunotherapy and RT are already ongoing, but clinical studies for this combination in thymoma are lacking. © Translational lung cancer research. All rights reserved.

Chirinos J.A.,University of Pennsylvania | Chirinos J.A.,Perelman Center for Advanced Medicine
Journal of Cardiovascular Translational Research | Year: 2017

A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population. Our therapeutic approach to HFpEF can be enhanced by clinical phenotyping tools with the potential to “segment” this population into relevant pathophysiologic categories or to identify individuals exhibiting prominent specific abnormalities that can be targeted by pharmacologic interventions. This review describes relevant technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. In an accompanying review, the potential of this approach to enhance our clinical and therapeutic approach to HFpEF is discussed. © 2017 Springer Science+Business Media New York

Piette E.W.,Perelman Center for Advanced Medicine | Werth V.P.,Perelman Center for Advanced Medicine | Werth V.P.,Philadelphia Va Medical Center
Immunology and Allergy Clinics of North America | Year: 2012

Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. © 2012 Elsevier Inc.

Dutz J.,University of British Columbia | Werth V.P.,Philadelphia Medical Center | Werth V.P.,University of Pennsylvania | Werth V.P.,Perelman Center for Advanced Medicine
Journal of Investigative Dermatology | Year: 2011

Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patientssmokers and nonsmokerswho have milder cutaneous lupus. Agreement on a single, validated disease severity measure for CLE would permit comparisons among studies and thereby foster progress in the field. © 2011 The Society for Investigative Dermatology.

Privette E.D.,Perelman Center for Advanced Medicine | Privette E.D.,University of Pennsylvania | Werth V.P.,Perelman Center for Advanced Medicine | Werth V.P.,University of Pennsylvania
Current Opinion in Rheumatology | Year: 2013

PURPOSE OF REVIEW: Cutaneous Lupus Erythematous (CLE) is an autoimmune disease in which patients may present with isolated skin findings or have CLE associated with underlying systemic disease. The most significant recent studies on its pathogenesis and therapeutic management are reviewed here. RECENT FINDINGS: Patients with subacute and Discoid Lupus Erythematous had elevated Interferon score, about a third of all cases of SCLE could be attributed to previous drug exposure, and smoking may be more closely associated with CLE than Systemic Lupus Erythematous (SLE). An underlying genetic defect in some subsets of CLE patients may also be shared with SLE. Efficacy of antimalarial therapy is enhanced by increasing treatment duration or maintaining higher blood drug concentrations. Combination antimalarials that include quinacrine, thalidomide analogs, and Mycophenalate Mofetil may also be effective in refractory CLE. SUMMARY: The pathogenesis of CLE remains unclear, and is likely multifactorial. Identified associations with subsets of CLE suggest future research questions in CLE pathogenesis. Subsets of CLE associated with interface dermatitis may share an underlying genetic defect in interferon signaling with SLE. The Cutaneous Lupus Disease Area and Severity Index is a valuable and widely used tool allowing standardized assessment and reporting of cutaneous disease activity and damage. More evidence is available to guide treatment of refractory CLE, but larger studies are needed. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.

Fett N.,Philadelphia Medical Center | Fett N.,University of Pennsylvania | Fett N.,Perelman Center for Advanced Medicine | Liu R.H.,University of Wisconsin - Madison
Dermatology | Year: 2011

Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans histiocytosis that presents with erosive arthritis and skin nodules. Approximately 25% of patients with MRH have an associated malignancy. Dermatomyositis is an inflammatory autoimmune condition that has also been associated with malignancy. To date, 7 cases of MRH have been reported to present with cutaneous features of dermatomyositis. We describe an eighth patient with MRH who presented with dermatomyositis-like features (V-neck erythema, shawl sign, Gottron's papules and periungual erythema), who developed metastatic breast cancer 1 year after diagnosis. We hypothesized that clinical overlap between MRH and dermatomyositis was not as uncommon as review of the literature suggested. Careful review of the physical exam findings and photographs of the 234 papers reporting MRH revealed 27 cases of MRH with dermatomyositis-like features. Of these 27 cases, 7 (26%) were associated with a malignancy. Skin biopsies of the cutaneous features mimicking dermatomyositis revealed pathologic features of MRH. This is a descriptive analysis of published case reports. Based on a review of published case reports, MRH presenting with dermatomyositis-like features is likely fairly common. Histological examination of skin biopsies allows for disease differentiation. Differentiating MRH from dermatomyositis is important for management decisions and comorbidity screening. Copyright © 2011 S. Karger AG, Basel.

Okon L.G.,Perelman Center for Advanced Medicine | Werth V.P.,Perelman Center for Advanced Medicine
Best Practice and Research: Clinical Rheumatology | Year: 2013

Cutaneous lupus erythematosus (CLE) encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several sub-types, including acute CLE (ACLE), sub-acute CLE (SCLE) and chronic CLE (CCLE). CCLE includes discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain cutaneous lupus and lupus tumidus. The diagnosis of these diseases requires proper classification of the sub-type, through a combination of physical examination, laboratory studies, histology, antibody serology and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. The treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring or treatment-refractory disease. In this chapter, we discuss issues in classification and diagnosis of the various sub-types of CLE, as well as provide an update on therapeutic management. © 2013 Elsevier Ltd. All rights reserved.

Socinski M.A.,University of Pittsburgh | Socinski M.A.,5150 Center Ave | Evans T.,Perelman Center for Advanced Medicine | Gettinger S.,Yale Cancer Center | And 4 more authors.
Chest | Year: 2013

Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the presence of specific genetic mutations. Copyright © by the American College of Chest Physicians 2013.

Freedman G.M.,Perelman Center for Advanced Medicine
Current Oncology Reports | Year: 2012

Hypofractionated radiation refers to the use of fewer, larger-dose radiation treatments that are usually given over a shorter time period compared to conventional radiation fraction sizes. Randomized trials of hypofractionated whole breast irradiation (WBI) have demonstrated comparable outcomes as conventional fractionation. For a higher-risk population for local recurrence, a phase 3 trial by the Radiation Therapy Oncology Group (RTOG) is currently studying hypofractionated WBI with a concurrent tumor bed boost over 3 weeks. Accelerated partial breast irradiation limits radiation to the region of the tumor bed for 1-3 weeks and is the subject of an ongoing randomized trial by the National Surgical Breast and Bowel Project and RTOG. Questions remain for hypofractionation about optimal patient selection, radiation techniques, and the risk of late toxicity. But results from current trials could make hypofractionation more widely accepted for patients with early-stage breast cancer. © 2011 Springer Science+Business Media, LLC.

Lattimer J.G.,Perelman Center for Advanced Medicine
Clinical Journal of Oncology Nursing | Year: 2013

A national work group met in 2004 to discuss the future of advanced practice nursing. The representatives were nursing education, certification, accreditation, and regulation experts, and the goal was to develop a consensus model for advanced practice nursing regulation (Nevidjon et al., 2010). As a result, a set of recommendations was published in an article that defined a new consensus model for advanced practice registered nurse (APRN) regulation (APRN Consensus Workgroup, 2008; Goudreau, 2009). The new model included six population-based focuses of practice (i.e., family and individual across the lifespan, adult and gerontology, neonatal, pediatrics, women's health- and gender-related, and psychiatric and mental health) (Johnson, Dawson, & Brassard, 2010). A goal of the new model was to standardize the licensure, certification, and regulation of nurse practitioners into specific focuses. State boards were facing an increasing number of requests to recognize nurse practitioner specialties (e.g., organ specific, body systems, diseases) (Johnson et al., 2010). The new model helped standardize education programs, which may help certifying agencies set up curriculum review processes to ensure appropriate credentials for APRNs (Johnson et al., 2010). It also supported the mission of nursing to meet future healthcare needs of the public and to protect the public (Johnson et al., 2010). Some advantages exist to delineating into population-based focuses, but the new model leaves out many specialties (e.g., oncology) that encompass the whole person as well as concentrate on certain diseases. © Oncology Nursing Society.

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