HSS Rheumatology Annual Report 2012-2012 by Hospital for Special Surgery

THE POWER AND POTENTIAL OF RESEARCH Division of rheumatology

2011-2012 Annual Report

The Division of Rheumatology at Hospital for Special Surgery is the largest program of its kind in the United States with 25 rheumatologists, four pediatric rheumatologists, five physicianscientists, and 14 rheumatology fellows. The Division is highly regarded throughout the world as a leader in research and treatment of autoimmune and rheumatic diseases. Its clinicians and scientists are committed to a three-pronged mission of providing outstanding clinical care and services; conducting basic, clinical, and translational research; and training residents and fellows and introducing medical students to the field.

On the cover: Alessandra B. Pernis, MD, a senior scientist in the Division of Rheumatology, conducts studies in animal and genetic models of rheumatoid arthritis and lupus to better understand the regulation of inflammation and autoimmunity.

Contents Leadership Report

Centers of Excellence Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Osteoarthritis

Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Scleroderma, Vasculitis, and Myositis

Metabolic Bone Disease and Osteoporosis

Pediatric Rheumatology

Professional Staff

endowed Chairs, Professorships, and Fellowships 19 2011-2012 Notable Achievements

2011-2012 Selected Publications

Contact Information

Tumor necrosis factor (TNF), an inflammatory cytokine that plays a significant role in immune responses, activates cells through its two receptors â&#x20AC;&#x201C; TNF receptor 1 (TNFR-1) and TNFR-2. Antibody-based therapy against TNF is used clinically to treat several autoimmune diseases. This 3D model shows a TNF trimer associated with a TNF receptor trimer.

Leadership Report: A message from the physician-in-chief and chairman, division of Rheumatology

During the past year, the Division of Rheumatology at Hospital for Special Surgery marked a period of noteworthy accomplishments in a number of areas. Each of our centers of excellence continued to pursue research and clinical initiatives, making major inroads in treatment approaches that can be offered to our patients – both in clinical trials and in practice. In 2011, rheumatology patient visits totaled 31,700, with another 4,169 visits made to pediatric rheumatologists. The Division also realized a 20 percent increase in patient volume in year-to-date 2012 over 2011. I am pleased to report that over the last three years, the Division’s Press Ganey patient satisfaction scores have steadily increased overall, with scores in the 90s. We continue to enhance care and services for our patients and, most recently, we initiated a rheumatology fast track program that provides a central phone number for patient referrals. During the patient’s call, a staff member conducts a screening assessment and schedules an appointment with the appropriate rheumatologist within 10 days. In the first three months of the program more than 200 patients utilized this service. In addition, we launched a nonoperative osteoarthritis (OA) triage program in which new OA patients are screened in order to optimize referrals to the relevant medical or surgical specialist. To meet the ever-increasing demand of patients seeking our care, the Division of Rheumatology underwent a major expansion and renovation project that has nearly doubled clinical and practice space, as well as added facilities to accommodate new physicians and staff for our increasing number of patient registries. In addition, our pediatric rheumatology patients are benefitting from a completely new pediatric inpatient and outpatient environment with the opening of the CA Technologies Rehabilitation Center in 2011, and the Alfred and Norma Lerner Children’s Pavilion, which opened in 2012. Our Perioperative Medicine Division, under the direction of Linda A. Russell, MD, is maximizing the health of surgical patients whose comorbidities may increase their operative risk. The Division, which has seen an 18 percent increase in perioperative medicine patient volume year to date in 2012, currently has 19 faculty members – eight rheumatologists who have significant perioperative

Division of Rheumatology

medicine practices and 11 internists, including the Hospital’s night and weekend hospitalists. The Division is currently recruiting additional hospitalists and internists to join this important and growing program.

Mary K. Crow, MD

Working closely with nursing staff, our perioperative physicians have established a number of medical guidelines for pre- and postoperative care, including those related to diabetes, anemia, and heart disease. Dr. Russell and her colleagues are also participating in the POISE II Trial – an international, multisite study of patients undergoing major, noncardiac surgery, including joint replacement and spine surgeries, to look at mortality or nonfatal myocardial infarction in patients with, or at risk of, atherosclerotic disease. To determine if preoperative home visits by nurses can facilitate recovery after surgery, Dr. Russell and her perioperative team are conducting a study in which nurses will make home visits to 100 patients to assess their home environment. Their evaluation will be provided to the Hospital’s case managers, who will determine if it is safe for the patient to return home or if an alternative discharge plan is required following surgery. The clinical practices of our rheumatologists are enhanced by a skilled and experienced nursing staff. HSS once again received Magnet designation in 2011 – the first hospital in New York State to achieve its third consecutive designation as a Magnet hospital by the American Nurses Credentialing Center. Magnet recognizes healthcare organizations for quality patient care, nursing excellence, and innovations in professional nursing practice. HSS has maintained Magnet status since 2002. Patient education and support is a mainstay of our rheumatology programs and centers of excellence. In a new initiative, Robert F. Spiera, MD, assisted by research assistant Kamini Doobay, has spearheaded the first narrative medicine journal devoted to rheumatology, which will be for, by, and about our patients and their

Rheumatology Education

caregivers. The journal will include poetry, photography, and prose related to health, healing, navigating illness, mind, body, and/or self-transformations. In 2011 Laura Robbins, DSW, Senior Vice President of Education and Academic Affairs and Associate Scientist at HSS, received the Lifetime Achievement Award from the Association of Rheumatology Health Professionals (ARHP), a division of the American College of Rheumatology. ARHP’s highest honor, the award recognizes Dr. Robbins for a career demonstrating a sustained and lasting contribution to the field of rheumatology and rheumatology health professionals.

“Education has gained growing interest within the field of rheumatology,” says Anne R. Bass, MD, Program Director of the Rheumatology Fellowship Program, and member of the HSS Rheumatology Education Council at HSS. “Rheumatology educators are beginning to ‘step up their game’ in practicing education in an evidenced-based way.”

The Division of Rheumatology, as you will read in this report, embraces disease-focused research at the basic, translational, and clinical levels. We are fortunate to have rheumatologist Steven Anne R. Bass, MD Jessica R. Berman, MD R. Goldring, MD, at the helm of the Hospital’s Research Division. In 201l, Dr. Goldring was The Academy of Rheumatology Medical Educators, named the first Richard L. Menschel Research Chair at HSS. established in 2011 under the leadership of Steven The chair, established by a $5 million gift from an anonyA. Paget, MD, and Jessica R. Berman, MD, Associate mous donor, honors Mr. Menschel, Chairman Emeritus of Director of the Rheumatology Fellowship Program, HSS, who has been a steadfast supporter of the Hospital’s broadened its scope beyond HSS, inviting clinicians research efforts. The gift permanently endows the position from NewYork-Presbyterian Hospital, The Rockefeller of the Hospital’s Chief Scientific Officer. University, and Memorial Sloan-Kettering Cancer Under Dr. Goldring’s leadership, the Hospital’s current research portfolio has grown to $21 million, including $15.4 million in federal funding. He has established major research objectives focused on translating basic research into new therapies for our patients, and, to date, the Hospital has 43 active patient registries with an enrollment of some 84,000 patients for both rheumatology and orthopaedic surgery research. The Division of Rheumatology is currently developing two new patient registries – an inflammatory arthritis registry and a nonoperative registry of patients with osteoarthritis. Within their specialties and across disciplines, our rheumatologists and scientists collaborate to ensure that discoveries that better our understanding of rheumatic diseases can be expedited to the clinical arena. This is evident in our Inflammatory Arthritis Center, where the breadth of research activities spans from scientists examining the biologic causes of inflammation and

Center to participate. This year, the Academy initiated a pilot program funding three peer-reviewed education research grants: C. Ronald MacKenzie, MD, to create a course on ethics as it relates to patients with disabilities; Dr. Berman for her work on ROSCE (rheumatology objective structured clinical exam); and Juliet B. Aizer, MD, MPH, and Lisa A. Mandl, MD, MPH, to expand on a trainee journal club on epidemiological research. “The grant proposals were formally vetted by educators chosen from a national pool,” says Dr. Bass. “The submissions were really terrific, and the quality of the critiques from the outside evaluators quite impressive.” Other Academy initiatives include incorporating educational topics into the Division’s Grand Round series; the creation of an education journal club; and an Academy Day where researchers who have received grants will present their findings.

Division of Rheumatology

From mouse Models to Human studies

various immune responses to clinicians working sideby-side with surgeons to identify predictors of risk and implement protocols to optimize the surgery and recovery of patients with rheumatic and autoimmune diseases. Research in systemic lupus erythematosus and antiphospholipid syndrome is expanding our knowledge base at the molecular and clinical levels. The PROMISSE lupus pregnancy study continues to uncover new avenues for potential treatment of pregnancy-related complications, and, more recently, genetic studies of patients with placental inflammation have begun that may improve our understanding of lupus nephritis. In our Scleroderma, Vasculitis, and Myositis Center, patients facing the multiple challenges of scleroderma are finding help through a number of major investigator-initiated and NIHsupported multicenter clinical trials underway at HSS. Our physicians serve as the Division of Rheumatology for NewYork-Presbyterian Hospital/Weill Cornell Medical Center and each of our members is on the faculty of Weill Cornell Medical College. Our affiliation with Weill Cornell has fostered longstanding and productive clinical, academic, and scientific partnerships and, with the appointment of Laurie H. Glimcher, MD, a prominent rheumatologist and clinician-scientist, as the Stephen and Suzanne Weiss Dean of the Medical College, we look forward to strengthening these collaborations even further. Since taking on the role of Chairman of Rheumatology, I have had the pleasure of working with my HSS colleagues to expand and reorganize the Division’s clinical and research enterprise. I hope you enjoy reading about our progress and the research and clinical advancements that our Division has made in the last year to improve care for patients with rheumatic disease.

Mary (Peggy) K. Crow, MD Physician-in-Chief and Chairman, Division of Rheumatology Benjamin M. Rosen Chair in Immunology and Inflammation Research Hospital for Special Surgery Joseph P. Routh Professor of Rheumatic Diseases in Medicine Weill Cornell Medical College

Division of Rheumatology

At the 25th anniversary celebration for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Jane E. Salmon, MD, one of Special Surgery’s leading research scientists, was chosen to give a presentation on how unconventional hypotheses can lead investigators to discoveries that have significant impact on patient care.

Jane E. Salmon, MD

Just such an approach was undertaken by Dr. Salmon, who developed data in animal models about the critical role of complement proteins that allowed her to launch the PROMISSE study, an initiative that has expanded knowledge about pregnancy in patients with lupus. According to Dr. Salmon, Collette Kean Research Chair, PROMISSE validates the importance of using animal models to study human disease. “Without our findings in mice, nobody would have considered complement as a mediator of pregnancy complications in lupus patients,” says Dr. Salmon. “This was entirely unconventional. Complement proteins have been considered as useful primarily to fight off infections. The notion that they could play a key role in pregnancy complications was revolutionary.” With funding from NIAMS, Dr. Salmon and her colleagues at HSS developed a mouse model of lupus by injecting pregnant mice with antiphospholipid antibodies. “Antiphospholipid antibodies are the strongest predictor of pregnancy loss and complications in lupus,” says Dr. Salmon. “What we discovered unexpectedly was that the complement cascade was critical to mediating damage. When there is inappropriate complement cascade activation, there can be tissue damage.” Further research showed that by inhibiting complement, they could save pregnancies in mice. Nearly a decade later, the PROMISSE study has made significant contributions to the clinical sphere of lupus pregnancy. (See page 10.) Dr. Salmon’s lecture can be viewed in its entirety on the NIAMS 25th anniversary website: www.niams. nih.gov/25th_Anniversary/Symposium.asp.

Center of Excellence: Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

professional staff

Juliet B. Aizer, MD, MPH Dalit Ashany, MD Anne R. Bass, MD Vivian P. Bykerk, MD * Stephen J. Di Martino, MD, PhD Theodore R. Fields, MD, FACP Allan Gibofsky, MD, JD, FACP, FCLM * Steven R. Goldring, MD, MACR Richard L. Menschel Research Chair Susan M. Goodman, MD * Jessica K. Gordon, MD Xiaoyu Hu, MD, PhD Lionel B. Ivashkiv, MD David H. Koch Chair for Arthritis and Tissue Degeneration Research George D. Kalliolias, MD, PhD * Steven K. Magid, MD Lisa A. Mandl, MD, MPH Charles L. Christian, MD, Research Fellow Joseph A. Markenson, MD, FACP, MACR Charis F. Meng, MD Dana E. Orange, MD * Stephen A. Paget, MD, FACP, MACR Stephen A. Paget, MD, Chair in Rheumatology Edward J. Parrish, MD Sergio Schwartzman, MD * Franchellie M. Cadwell Chair Lisa C. Vasanth, MD, MS Allied Health Professionals Adena Batterman, MSW, LCSW * Emily Dorfman, LMSW Su Jin Kim, LCSW Juliette Kleinman, LCSW, ACSW Kathryn Klingenstein, LMSW Linda Leff, RN, BSN, BC * * Members of Center Oversight Committee

Inflammatory Arthritis Center

Sergio Schwartzman, MD Clinical Director Vivian P. Bykerk, MD Research Director

The Division of Rheumatology’s multipronged Inflammatory Arthritis Center, under the co-direction of Sergio Schwartzman, MD, and Vivian P. Bykerk, MD, continues to be a model of collaboration among the physicians who treat patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, and autoimmune ophthalmic illnesses, and the physicians and scientists who study their causes at the most basic level and bring their findings into clinical practice. Pursuing Fundamental Studies in Inflammatory Arthritis In the Arthritis and Tissue Degeneration Program, important strides are being made by Carl P. Blobel, MD, PhD, Program Director, and Lionel B. Ivashkiv, MD, Associate Chief Scientific Officer at HSS and head of the Laboratory of Cytokine Signaling and Inflammation, in understanding the role of tumor necrosis factor (TNF) in inflammatory disease. Dr. Blobel studies ADAMS, a family of molecules that regulates many cell activities, including the functions of TNF alpha (TNFα). When produced in excess, TNFα causes inflammation and many of the systemic manifestations and tissue damage associated with inflammatory diseases. ADAM 17, also called TNFα convertase or TACE, releases TNFα from the cells, stimulating an immune response that attacks various tissues. Dr. Blobel has been exploring the inhibition of TACE as a potential therapeutic strategy for treating autoimmune and inflammatory diseases and, most recently, he and his colleagues have identified a potential mechanism to inactivate TACE in immune cells only without affecting its function in other organs. This opens the door to the possibility of treatments with small molecules that would be taken as pills, cause fewer Sergio Schwartzman, MD side effects, and be less expensive than current therapies. Dr. Ivashkiv and his colleagues recently investigated the mechanisms that mediate the beneficial actions of inhibitors of Janus kinases (JAKs), which have been developed as anti-inflammatory and immunosuppressive agents and are currently undergoing testing in clinical trials for the treatment of RA. Examining the effects of several JAK inhibitors on inflammatory and TNF responses in human macrophages, they demonstrated that JAK inhibitors suppress macrophage activation and attenuate TNF responses, and that suppression of cytokine/ chemokine production and innate immunity contributes to the therapeutic efficacy of JAK inhibitors. A new study led by Xiaoyu Hu, MD, PhD, in the Laboratory of Cellular Signaling and Immune Regulation at HSS, has identified the mechanism by which the (continued on page 6)

Division of Rheumatology

INFLAMMATORY ARTHRITIS REGISTRY (continued from page 5)

Notch intracellular molecular pathway, known to be involved in cancer, also contributes to the development of RA. Working with researchers at other institutions in the United States and abroad, HSS investigators sought to find out how Notch is involved, hypothesizing that it might prompt a misfiring of the immune system that is commonly seen in RA. The researchers found that knockout mice that lack the Notch pathway were unable to produce certain types of macrophages critical for human RA pathogenesis and exhibited a lesser inflammatory phenotype. The study not only provides the first explanation of Notch’s connection to RA, it also shows, for the first time, that investigational Notch inhibitors under development for cancer and Alzheimer’s disease – with some already in clinical trials – could potentially be used to treat RA. Tapping the Talents of Clinical Researchers Vivian P. Bykerk, MD, who is the Director of the Consortium of Early Arthritis Cohort Studies, a group of observational research studies in early RA in North America, also participates in OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials), an independent initiative of international health professionals interested in outcome measures in rheumatology. Her research interests are in identifying predictors for and best practices to improve outcomes in patients with new onset rheumatoid arthritis, and she is actively working with a number of other investigators in OMERACT to develop a measure of flare in RA. The Surgical Arthritis Service Research Group, a collaboration of the Hospital’s rheumatologists and orthopaedic surgeons under the direction of Susan M. Goodman, MD, has been extremely productive since its

Susan M. Goodman, MD

Division of Rheumatology

Vivian P. Bykerk, MD

A major focus of the Inflammatory Arthritis Center (IAC) is to develop patient registries for RA, ankylosing spondylitis, and other inflammatory diseases. This effort has been expanded with the recruitment in 2011 of rheumatologist Vivian P. Bykerk, MD, who has been named Research Director of the IAC. A clinical researcher from Mount Sinai Hospital in Toronto, Canada, Dr. Bykerk has been leading a longterm observational multicenter study of how to best treat patients with new onset inflammatory arthritis and ensure their early access to care. Dr. Bykerk is developing a clinical research program to study patients with new onset RA with a patient registry in early inflammatory arthritis at its core. With the registry at HSS expected to be operational in 2013, she plans to engage investigators across the country who have already expressed interest in participating in the development of the first multicenter registry for early inflammatory arthritis and collaborating on nationwide studies of this patient population. The objective is to investigate predictors of RA progression and therapeutic response with the goal of developing a prediction tool to help clinicians and patients make decisions about therapy early. Dr. Bykerk, along with Susan M. Goodman, MD, and Lisa A. Mandl, MD, MPH, will also be creating a new registry at HSS in spondylitis to identify novel biomarkers in patients that can help identify predictors of severe disease.

inception less than two years ago. Dr. Goodman, along with Lisa A. Mandl, MD, MPH, and orthopaedic surgeons Mark P. Figgie, MD, and Michael M. Alexiades, MD, continues to explore perioperative outcomes of rheumatic disease patients. With a number of projects underway, their research has already demonstrated that: • R A patients do not have an increase in early adverse events after total knee replacement • a marked difference exists in perioperative outcomes in systemic lupus erythematosus (SLE) cases undergoing total knee replacement (TKR) compared to total hip replacement (THR); TKR patients were similar to the osteoarthritis controls, while the SLE THR patients were younger, sicker, and had greater comorbidity Additional studies in progress include assessments of arthroplasty outcomes in psoriatic arthritis, ankylosing spondylitis, and inflammatory muscle disease, as well as the effect of pregnancy on THR. The work of the Surgical Arthritis Service Research Group has expanded through collaborations with anesthesiologists Stavros G. Memtsoudis, MD, PhD, at HSS, and Otto Stundner, MD, at Salzburg University Hospital. Through exploration of large databases, they have demonstrated that RA THR patients have a significant increase in background COPD and perioperative pulmonary and infectious complications, as well as greater transfusion requirements, compared to OA patients. No increase in cardiac disease was observed. The RA TKR cases similarly had an increase in infection and transfusion requirements, but no increase in perioperative pulmonary or cardiac complications. A study by Lisa A. Mandl, MD, MPH, and her colleagues has shown that the timing of withdrawing anti-TNF medications in patients with RA before total knee replacement might potentially impact rates of postoperative flares. They recommend that additional studies are needed to evaluate if the half-lives of the medications should be considered more carefully when determining when to stop the drugs before a procedure to optimize postoperative outcomes. Another study comparing expectations of RA patients with OA patients who undergo total knee replacement surgery has shown that RA patients have lower expectations about their postsurgical outcomes, raising a concern that these

reduced expectations could cause some patients to neglect their postsurgical rehabilitation and lead to worse outcomes. Mild heterotopic ossification (HO) is a common, although not universal, complication of hip replacement surgery. If severe, there is no Lisa A. Mandl, MD, MPH treatment other than surgical removal of the ossified tissue – an extremely difficult and morbid procedure. There are currently no biomarkers that can accurately identify patients who are at risk for the development of HO. Dr. Mandl is the principal investigator of a new study which seeks to define biologic and genetic risk factors and mechanisms that predispose certain individuals to develop HO after hip replacement. Importantly, the bone formation in HO is similar to the excess bone produced in ankylosing spondylitis (AS). HO therefore presents an interesting model that might also provide insights into AS – a disease that continues to present challenges to clinicians even in the era of biologic therapies. Education and Support for Early Arthritis Developing support and education programs for people who are within one year of being diagnosed with RA is considered of paramount importance by the Center’s physicians, nurses, and social workers. A detailed multilevel needs assessment, including input from patients, was undertaken to ensure that it would meet the needs of people who were recently diagnosed, since their needs could be very different from people who have been living with the disease for many years. The result was the creation of the Early RA Patient Support and Education Group and the Living with RA Support and Education Group. Co-facilitated by a nurse and a social worker, the groups meet monthly with the first hour of the program focusing on disease-related content delivered by physicians and health professionals; the second hour provides time for members to exchange ideas and resources and benefit from peer support. ■

Division of Rheumatology

Center of Excellence: Osteoarthritis

professional staff

Juliet B. Aizer, MD, MPH Dalit Ashany, MD Mary K. Crow, MD Benjamin M. Rosen Chair in Immunology and Inflammation Research Stephen J. Di Martino, MD, PhD Theodore R. Fields, MD, FACP Mary B. Goldring, PhD Ira W. DeCamp Fellowship in Musculoskeletal Genetics Steven R. Goldring, MD, MACR Richard L. Menschel Research Chair Brian C. Halpern, MD Jo A. Hannafin, MD, PhD Suzanne A. Maher, PhD supported by Russell F. Warren, MD, Research Chair Lisa A. Mandl, MD, MPH Charles L. Christian, MD, Research Fellow Joseph A. Markenson, MD, FACP, MACR Robert G. Marx, MD, MSc, FRCSC Charis F. Meng, MD Edward J. Parrish, MD Hollis G. Potter, MD Chase and Stephanie Coleman Chair in Magnetic Resonance Imaging Research Scott A. Rodeo, MD Jenny Scott, PhD Lisa C. Vasanth, MD, MS Hendricks H. Whitman III, MD Diana A. Yens, MD Allied Health Professionals Emily Dorfman, LMSW Su Jin Kim, LCSW Juliette Kleinman, LCSW, ACSW

At Hospital for Special Surgery, osteoarthritis (OA) has the attention at some level of more than 350 clinicians, clinical investigators, and basic scientists in the Division of Rheumatology, the Department of Orthopaedic Surgery, and the Research Division. Calling on the wide-ranging expertise in OA that exists within the Hospital, and with important support from the Starr Foundation, the development of an Integrated Osteoarthritis Diagnostic, Treatment, and Research Program is well underway. By assimilating the work of physicians and scientists in OA under one umbrella, the program seeks to further the basic understanding of this multi-factorial disease and expedite the development of clinical research that will lead to improved treatment outcomes and strategies for prevention. Intervening at the Pre-Clinical Level In the Hospitalâ&#x20AC;&#x2122;s basic science laboratories, advances continue to be made on understanding the factors contributing to the progression of OA and relating clinical outcomes to a biologic process. Mary B. Goldring, PhD, Director of the Laboratory for Cartilage Biology in the Tissue Engineering Repair and Regeneration Program at HSS, focuses her work on cartilage, including its formation during skeletal development, its destruction during OA, and its interactions with other joint tissues. A major challenge is the inability of the resident chondrocytes in cartilage to lay down a new matrix with the same properties as it had when it was formed during development. Thus, researchers in the field are looking for strategies to prevent cartilage damage in the first place or to repair the damaged cartilage with cell-based tissue-engineering approaches. Dr. Goldringâ&#x20AC;&#x2122;s laboratory has uncovered new roles of genes not previously known to act in cartilage and studies the mechanisms by which stress and inflammatory signals and changes in DNA methylation status induce expression of matrix metalloproteinase 13 (MMP-13), the pivotal collagen-degrading proteinase that marks OA progression. Dr. Goldring and her colleagues have found that there are common mediators of these processes in human OA cartilage and are profiling temporal and spatial changes in gene expression and microRNAs during early through late stages of OA in mouse models of post-traumatic and genetic forms of OA. These studies will lead to identification of critical targets for therapy to block initiation of cartilage damage or promote effective cartilage repair.

Lisa C. Vasanth, MD, MS

Division of Rheumatology

Suzanne A. Maher, PhD, and her colleagues continue to investigate the functional performance of meniscal repair scaffolds preclinically with a goal towards developing an early intervention for repairing soft tissue defects and thereby delay the progression of OA from an index injury. Most recently,

Frontiers in Osteoarthritis

Dr. Maher has been pursuing the development of synthetic implants that can be used as partial replacements for damaged cartilage tissue or as replacements for torn and damaged menisci that are able to transfer large loads across these complicated structures. She and her colleagues at HSS and around the country have developed a class of hydrogel materials that approximate the properties of the cartilage and meniscus and are currently testing them in pre-clinical models.

As the population ages, the prevalence, impact, and economic consequences of OA will increase dramatically. The factors that play a role in the initiation and progression of OA need to be translated into effective diagnostic, preventative, and treatment strategies, which can only be accomplished by a broad interdisciplinary approach. With this in mind, in June 2011, HSS hosted an international summit – Frontiers in OA Research, Prevention, and Care – led by Steven R. Goldring, MD, the Richard L. Menschel Research Chair and Chief Scientific Officer, and Timothy M. Wright, PhD, the F.M. Kirby Chair in Orthopaedic Biomechanics, and Director of the Department of Biomechanics.

Clinical Perspectives Lisa C. Vasanth, MD, MS, in collaboration with Hendricks H. Whitman III, MD, is leading the development of a registry of patients with OA of the knee who are managed without surgery. Knee osteoarthritis is the most common disabling condition, affecting an estimated 9.3 million people in the United States. The registry will monitor how patients respond to conservative treatment over time; provide an understanding of characteristics of patients who might respond to a particular type of therapy; help establish protocols for use of antiinflammatory medications, injections, bracing, and other modalities; and determine how these interventions work together for optimal management. The database builds on pilot data previously compiled by Brian C. Halpern, MD, Chief, Primary Steven R. Goldring, MD Timothy M. Wright, PhD Care Sports Medicine, on platelet-rich plasma The impressive assembly included scientific leaders, injections in patients with OA of the knee. clinicians, governmental officials responsible for At the same time, a comprehensive care program for aiding and directing research, representatives from patients with OA is under development to bring together major OA research societies and foundations, and rheumatologists, orthopaedic surgeons, sports medicine members of the pharmaceutical, device, and insurance physicians, physiatrists, physical therapists, nutritionists industries. On the agenda were discussions of the and other health professionals, which will not only optimize latest research, diagnostic tools, treatment approaches, and organize care for patients with OA, but also facilitate and strategies for prevention. An important outgrowth the expansion of the nonoperative knee registry. of the Summit is a proposal to develop a classification A new study under the direction of Howard Hillstrom, PhD, tree that identifies OA as spontaneous or induced, and colleagues in the Hospital’s Leon Root, MD, Motion and further classifies the disease based on symptoms, Analysis Laboratory is evaluating conservative realignment associated bone structural abnormalities, cartilage therapy for patients with OA in the medial compartment and related joint tissue abnormalities, and stage of of the knee to see if it helps relieve knee pain and improve disease progression. function. The goal is to gently alter individuals’ knee Consensus statements and analysis from the Summit alignment with a light and flexible custom-fitted knee brace. have been published in a series of papers in the HSS Based on previous studies, the researchers believe that Journal: The Musculoskeletal Journal of Hospital for realigning the knee using the custom brace can significantly Special Surgery, Volume 8, Issue 1. reduce pain and has the potential to slow the progression of osteoarthritis. ■

Division of Rheumatology

Center of Excellence: Systemic Lupus Erythematosus and Antiphospholipid Syndrome

professional staff

John W. Barnhill, MD Jessica R. Berman, MD Mary K. Crow, MD Benjamin M. Rosen Chair in Immunology and Inflammation Research Doruk Erkan, MD, MPH * Kyriakos A. Kirou, MD, DSc, FACP * Elizabeth Kozora, PhD Michael D. Lockshin, MD, MACR * Theresa T. Lu, MD, PhD * supported by St. Giles Research Chair Carol A. Mancuso, MD, MPH, FACP * Joseph A. Markenson, MD, FACP, MACR Stephen A. Paget, MD, FACP, MACR Stephen A. Paget, MD, Chair in Rheumatology Alessandra B. Pernis, MD * Peter Jay Sharp Chair in Lupus Research Jane E. Salmon, MD * Collette Kean Research Chair Lisa R. Sammaritano, MD * Allied Health Professionals Emily Dorfman, LMSW Su Jin Kim, LCSW * Juliette Kleinman, LCSW, ACSW Monica Richey, MSN, ANP-BC/GNP * Jillian Rose, LMSW Erica Sandoval, LMSW Nadine Spring, MPH * Julie Pollino Tanner, RN, MA * My-Lan Tran, LCSW * Members of Center Oversight Committee

Systemic Lupus Erythematosus and Antiphospholipid Syndrome Center of Excellence

Jane E. Salmon, MD Director

The Center of Excellence in Systemic Lupus Erythematosus and Antiphospholipid Syndrome is a model for providing integrative, multidisciplinary care and using clinical experiences and observations as a platform to expand the range of science that is pursued by its clinicians and scientists. Integrating Research and Practice The multicenter PROMISSE study led by Jane E. Salmon, MD, with co-principal investigators Michael D. Lockshin, MD, and Lisa R. Sammaritano, MD, is perhaps the quintessential example of the integration of science with clinical practice. Now in its ninth year, the nationwide study, funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, currently involves over 700 patients – 400 of whom have lupus – from nine centers in North America. The Jane E. Salmon, MD ongoing observational prospective clinical trial is comparing the pregnancies of women with aPL (antiphospholipid antibodies), lupus, both aPL and lupus, and healthy controls. In July 2012, PROMISSE had its first clinical research paper published on a recent study demonstrating that women who have a specific type of antibody that interferes with blood coagulation function are at risk for adverse pregnancy outcomes and that other antibodies in the same family thought to cause pregnancy complications do not put women at risk. According to Dr. Lockshin, lead author of the study, the paper identifies people who are at risk for pregnancy loss and, more importantly, those who are not at risk and who therefore do not need to be treated. The study examined the association between adverse pregnancy outcome and the presence of three different aPLs: lupus anticoagulant [LAC], anticardiolipin antibody [aCL] and antibody to ß2 glycoprotein I. An adverse pregnancy outcome was defined as otherwise unexplained fetal death after 12 weeks, neonatal death prior to discharge that was associated with complications of prematurity, preterm delivery prior to 34 weeks because of gestational hypertension, preeclampsia or placental insufficiency, and birthing a child that was small for its gestational age. The researchers found that LAC was the strongest predictor of an adverse pregnancy outcome and that high titer aCL alone does not provide substantial risk, which prior to this study was considered a potent predictor of risk. The study will allow the researchers to identify subsets of patients with the highest risk in whom to test new approaches and new drugs.

Division of Rheumatology

A case in point

Since the start of the PROMISSE study, its researchers have identified inflammatory proteins and anti-angiogenic factor proteins that predict complications; determined that different antiphospholipid antibody profiles predict risk during pregnancy in lupus patients who have them; and compiled data suggesting that if the disease is inactive as indicated by serology, the patient is likely to have an uncomplicated, successful pregnancy. All of this data are influencing physician practices, providing clinicians with important information in the counseling of their patients. Moving forward, Dr. Salmon and her colleagues have partnered with the Genome Institute at Washington University in St. Louis, which is sequencing 100 different genes related to this pathway in patients enrolled in PROMISSE to determine whether or not these genes are altered in a manner that would lead to a lower threshold and more exaggerated activation and whether they can provide predictors of poor outcomes. PROMISSE researchers are also collaborating with a national organization that investigates genes associated with total renal failure – a potential consequence of severe lupus disease – necessitating dialysis and/or transplant. Since inflammation in the kidney has similar pathMichael D. Lockshin, MD ways to inflammation in the placenta, if lupus patients have alterations in the pathway responsible for irreversible kidney damage, it may be possible to screen people early in their diagnosis for these mutations to try to prevent the onset of kidney disease. Alessandra B. Pernis, MD, and her colleagues are seeking to define the mechanisms that lead to the dysfunction of lymphocytes in lupus and other autoimmune diseases with a focus on a few critical molecules that control the activation of these lymphocytes. Their research revealed that the regulation of one of these molecules – Interferon

A recent single case report underscored the value of studies in animal models to the treatment of catastrophic antiphospholipid syndrome (CAPS) in the clinical setting. CAPS is characterized by histopathologic evidence of small vessel thrombosis, dysfunction of multiple organs occurring over a short period of time, and laboratory confirmation of the presence of antiphospholipid antibodies (aPL). The studies of Jane E. Salmon, MD, in animal models supported the hypothesis that a more targeted intervention, such as complement inhibition, may be an effective means to prevent aPL-induced thrombosis that is refractory to conventional therapy. The subject is a male patient who had uncontrollable blood clots that were causing strokes and resulted in the loss of both his legs. Given his recurrent and severe clinical manifestations, the lack of response to first- and second-line therapies, and the high mortality risk associated with CAPS, the patient was given an unconventional treatment – blockade of terminal complement activation with eculizumab. Long-term eculizumab treatment combined with continued anticoagulation therapy with lepirudin resulted in the normalization of platelet counts, and the patient has been in remission with no further thromboses. The case report shows proof of concept that supports the basis for the PROMISSE study – uncontrolled complement pathway activation leads to tissue injury by antiphospholipid antibodies – in this case, thrombosis; in PROMISSE, pregnancy complications – and the blockade of complements arrests disease.

regulatory factor 4 (IRF4) – is controlled by the Rho kinase (ROCK), which mediates T-cell inflammatory responses. Using murine models, they discovered that when they block this pathway, they decreased the production of IL-17 and IL-21, two cytokines that induce inflammation and are linked to many autoimmune-related diseases including lupus. Having demonstrated that ROCK inhibition ameliorates disease in MRL/lpr mice, a spontaneous model of lupus, (continued on page 12)

Division of Rheumatology

Center of Excellence: Systemic Lupus Erythematosus and Antiphospholipid Syndrome (continued from page 11)

Dr. Pernis, in collaboration with Dr. Salmon, is now translating her studies to the clinical arena. The results of a recent pilot study they conducted on a subset of 28 lupus patients indicated that the pathway Dr. Pernis studied in the animal model is also dysregulated in some patients with lupus.

“good guys” and the “bad guys” in terms of T cells. If they can uncover clues about the mechanism that regulates this balance, they could then set up assays to monitor the systems in patients and develop therapeutic targets to harness the positive effects and decrease the negative effects.

Drs. Salmon and Pernis have been awarded a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases to expand the study to more patients in order to confirm whether elevation of ROCK exists and whether certain compounds – in particular, statins – can inhibit the activity of this Alessandra B. Pernis, MD kinase and reverse T-cell dysfunction that leads to lupus. Statins were selected because they alter ROCK activity and abnormalities in this pathway have previously been linked to the development of cardiovascular disease. With the high incidence of cardiovascular disease remaining as one of the greatest challenges in lupus, it is conceivable that the kinase is not only dysregulated in the immune cells of lupus patients, but in their cardiovascular systems as well. Other compounds targeting ROCKs that could also be used in lupus are in the pipeline, with some already in Phase I clinical trials for other indications.

Promoting Physical Activity in Patients with Lupus Carol A. Mancuso, MD, has a particular interest in physical activity as a way to foster general health and well-being and improve cardiovascular risk. Paralleling a methodology she successfully developed in patients with asthma, Dr. Mancuso developed a study to look at patients with lupus – a population at very high risk for cardiovascular disease. While this risk is likely linked to an inflammatory process, a sedentary lifestyle can accentuate this risk. However, patients with lupus may avoid physical activity due to concern of triggering a flare.

In a corresponding study, the researchers explored the protective effects of the ROCK inhibitor fasudil in a distinct model of lupus, NZB/W F1 female mice, to assess the broad applicability of ROCK inhibition for the treatment of lupus. They found that the fasudil treatment significantly improved survival and decreased proteinuria, and significantly decreased serum anti-dsDNA autoantibody production, glomerular IgG and C3 deposition, and glomerulonephritis. The findings indicate that fasudil can ameliorate disease in NZB/W F1 female mice, suggesting that ROCK inhibition might be broadly effective for the treatment of lupus. Dr. Pernis and her colleagues have also been working on defining the balance in the immune system between the

Division of Rheumatology

Assembling a cohort of patients with lupus from the Hospital’s lupus registry, Dr. Mancuso first conducted interviews asking questions to find out from patients what they thought about physical activity and if they would acknowledge it as important as a way to foster overall good health. The open-ended questions included: What do you think the benefits of physical activity are? What are the drawbacks to physical activity? Do you think you engage in enough physical activity? What are the obstacles for you to participate in physical activity? She then asked participants to report on their actual physical activity levels – from walking to gym or formal sports activities – followed by a walking test in which stride length, distance, and symptoms were measured. While the participants reported that they were less physically active than age- and sex-matched peers, when they walked up and down the corridor the distances and stride lengths were exactly what one would expect for age- and sex-matched peers. This became the basis for a follow-up pilot study designed to improve physical fitness in patients with lupus through walking – the cornerstone of Dr. Mancuso’s work in physical activity. Her goal is to help patients identify how they can incorporate more physical activity – especially walking – into their daily routine. The participants each made a contract agreeing that they would walk more. With patients first walking on a treadmill, the researchers took

SLE Research and social work practice baseline measurements of cardiac output, pulse, and blood pressure. Over the course of six weeks, the participants were encouraged to increase the number of steps that they walked. At the end of the six-week period, the treadmill tests were repeated, showing marked improvement in cardiac function. Dr. Mancuso now plans to conduct the study in a larger group of patients over a longer period of time to evaluate sustainability of the positive results. APS ACTION On the Move Since its launch in 2010, APS ACTION (Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking) has made significant progress in its goal to develop an international collaborative approach to designing and conducting prospective large-scale multicenter clinical trials of patients with persistent and clinically significant antiphospholipid antibody (aPL) profiles. In 2012, the coalition launched its first two collaborative international projects: a randomized controlled trial of hydroxychloroquine in the primary thrombosis prevention of persistently aPL-positive but thrombosis-free patients without other systemic auto-immune diseases; and a web-based registry of aPL-positive patients with or without systemic autoimmune diseases, which will also include annual blood collection for aPL testing and future basic science studies. The APS ACTION Registry recruited its first patient at HSS in May 2012. With the addition of nine new centers that will participate in clinical research projects, the organization now has 40 members representing countries around the world. Doruk Erkan, MD, Chair of APS ACTION, and Dr. Michael Lockshin, who serves on the Executive Committee, recently attended the National Institutes of Health Roundtable on APS ACTION hosted by the NIH and the Office of Rare Disease Research. The organization was cited for its success in getting strong international, interdisciplinary collaboration in such a Doruk Erkan, MD, MPH short period of time. ■

My-Lan Tran, LCSW, Juliette Kleinman, LCSW, ACSW, Jillian Rose, LMSW, and Su Jin Kim, LCSW

The Hospital’s SLE and APS Registry and Repository, which contains over 1,100 patients, not only fosters important research, it also helps to bridge patients to resources for their psychosocial needs. As members of the Mary Kirkland Center for Lupus Care, social workers are integrating their skills and knowledge to optimize outcomes and provide support for patients in research studies. The Hospital’s research environment creates a powerful context for social work assessment and intervention. In the PROMISSE study, social workers advocate for patients during their pregnancies, mediating difficult conversations about high-risk factors. In studies of cognition and lupus, they help identify practical coping strategies for patients with cognitive changes. In a study assessing factors influencing appointment compliance rates, social workers find solutions for barriers that can increase patient adherence. In a study of a patient counseling program for cardiovascular disease, they intervene to evaluate and encourage patients’ participation in pursuing relevant lifestyle changes in nutrition and exercise. In a study piloting a depression screening tool, they can intervene early to improve health outcomes. To read the full article: Kim SJ, Persad P, Erkan D, Kirou K, Horton R, Salmon JE. Research studies and their implications for social work practice in a multidisciplinary center for lupus care. Social Work in Health Care. 2012. Vol. 51, Issue 7:652-60.

Division of Rheumatology

Center of Excellence: Scleroderma, Vasculitis, and Myositis

professional staff

Anne R. Bass, MD, FACP Mary K. Crow, MD * Benjamin M. Rosen Chair in Immunology and Inflammation Research Stephen J. Di Martino, MD, PhD * Jessica K. Gordon, MD * Kyriakos A. Kirou, MD, DSc, FACP Michael D. Lockshin, MD, MACR Theresa T. Lu, MD, PhD supported by St. Giles Research Chair Steven K. Magid, MD Charis F. Meng, MD Stephen A. Paget, MD, FACP, MACR Stephen A. Paget, MD, Chair in Rheumatology Alessandra B. Pernis, MD * Peter Jay Sharp Chair in Lupus Research Robert F. Spiera, MD * Horatio F. Wildman, MD Allied Health Professionals Christie Custodio-Lumsden, MS, RD Emily Dorfman, LMSW * Suzan Fischbein, LMSW John Indalecio, OTR/L, CHT Su Jin Kim, LCSW * Juliette Kleinman, LCSW, ACSW Nina Paddu, BA Elizabeth Soto-Cardona, BA Uzunma Udeh, BA Aviva Wolff, OTR, CHT * Members of Center Oversight Committee

Scleroderma, Vasculitis, and Myositis Center of Excellence

Robert F. Spiera, MD Director

Under the leadership of Robert F. Spiera, MD, clinical, research, and fellowship education programs in scleroderma, vasculitis, and myositis have flourished. A growing clinical research program has garnered funding from federal, foundation, private, and industry sources for scleroderma and vasculitis research. The majority of the research studies are investigator-initiated clinical trials, including the largest cohort and longest study of scleroderma patients at any center addressing the safety of treatment with imatinib. Research continues apace on tyrosine-kinase inhibitors in the treatment of scleroderma. This year, Dr. Spiera, Jessica K. Gordon, MD, and their colleagues completed an open-label extension of the imatinib trial, providing patients with another two years of therapy. The study showed that patients on the extension trial did continue to improve, however, this may not be attributed to the medication as skin issues related to scleroderma, in the later phases, have been shown to improve on their own. They have also just completed the first phase of an investigator single site open-label trial at HSS of a new tyrosine-kinase inhibitor, nilotinib, in 10 patients with early progressive scleroderma showing Robert F. Spiera, MD that the drug is extremely welltolerated with fewer side effects than other tyrosine-kinase inhibitors related to fluid retention and gastrointestinal complaints. With a preliminary indication that patients may have improvements on this drug, a randomized, controlled trial is now needed. Dr. Gordon recently received a Clinical Scientist Career Development Award, which is given by the Hospital to scientists who have developed well-defined research programs integrated with clinical responsibilities in their respective fields. The five-year grant award is enabling her to investigate the gene expression profiles of skin and peripheral blood mononuclear cells using microarray techniques to assess disease activity and treatment response in scleroderma patients treated with tyrosine kinase inhibitors. Dr. Gordon will be using clinical and translational data from the various trials conducted at HSS in conjunction with the gene array data to try to predict clinical response. Dr. Gordon is also the recipient of a Scleroderma Foundation New Investigator Award. HSS is the first center conducting an investigator-initiated randomized, doubleblinded trial with belimumab â&#x20AC;&#x201C; the first biologic therapy approved for lupus that depletes B cells â&#x20AC;&#x201C; to determine its safety, efficacy, and tolerability for the treatment of scleroderma.

Division of Rheumatology

Jessica K. Gordon, MD

Stephen J. Di Martino, MD, PhD

In addition, faculty are involved in a number of industrysponsored multicenter trials evaluating the efficacy of drugs to treat diffuse cutaneous systemic sclerosis and digital ulcers, among others.

in 2012. Like Dr. Gordon, Drs. Forbess and Bernstein pursued research in scleroderma during their fellowships at HSS.

To date, steroids have been the only available treatment effective for the treatment of polymyalgia rheumatica (PMR), a painful inflammatory disease of the elderly. Dr. Spiera has been conducting the first clinical trial of tocilizumab to determine its safety, tolerability, and efficacy in patients with PMR. The investigator-initiated, open-label trial is actively enrolling patients who will receive tocilizumab in addition to steroids, but the steroids will be tapered more quickly than what would normally be done in practice. The drug inhibits the cytokine IL-6, which is considered central to the pathophysiology of the disease. Dr. Spiera also serves as the site principal investigator (PI) for an NIH-funded multicenter clinical trial for large vessel vasculitis to provide data on the efficacy of abatacept to prolong relapse-free survival in patients with giant cell atertitis and Takayasu’s arteritis. He is also the site PI for an NIH-sponsored vasculitis DNA study to provide clinical data and genetic information on patients with vasculitis. As a rheumatology fellow, Dr. Gordon received the Distinguished Fellows Award from the American College of Rheumatology (ACR) in 2009. That tradition continued with the awarding of the Distinguished Fellows Award to Lindsy J. Forbess, MD, in 2011, and to Elana J. Bernstein, MD,

In 2012, Drs. Spiera and Gordon were named to the Scleroderma Foundation National Medical Advisory Board. Dr. Spiera continues to serve as Chairman of the Medical and Scientific Advisory Board for the Scleroderma Foundation Tri-State Chapter and as a medical consultant and member of the Scientific Advisory Board for the Vasculitis Foundation. Stephen J. Di Martino, MD, PhD, focuses his clinical practice and research efforts on inflammatory muscle disease – idiopathic inflammatory myopathy and myositis – caring for patients and establishing a myositis patient registry that will support studies of this rare disease. Most recently, Dr. Di Martino has been using musculoskeletal ultrasound to aid in the diagnosis of inflammatory muscle disease. Promoting Education and Community Outreach The Scleroderma, Vasculitis, and Myositis Center has made a major commitment to patient education and community outreach. Over the past few years, the Center has established a formal program of e-newsletters, news blasts, forums, and monthly scleroderma support groups sponsored by the Tri-State Chapter of the Scleroderma Foundation. These programs seek to improve the understanding of methods and means to manage multiple aspects of scleroderma, myositis, and vasculitis and keep patients informed of recent developments in the broader research communities, as well as within the Center. ■

Division of Rheumatology

Center of Excellence: Metabolic Bone Disease and Osteoporosis

professional staff

Juliet B. Aizer, MD, MPH Dalit Ashany, MD Richard S. Bockman, MD, PhD Steven R. Goldring, MD, MACR Richard L. Menschel Research Chair Lionel B. Ivashkiv, MD David H. Koch Chair for Arthritis and Tissue Degeneration Research Joseph M. Lane, MD Martin Nydick, MD Linda A. Russell, MD Allied Health Professional Patricia Spergl, MSN, RN, ANP-BC

Osteoporosis Center of Excellence

Linda A. Russell, MD

Division of Rheumatology

HSS physicians and nurses have developed a new clinical pathway to better identify those with bone disease and those at risk in order to map the course for proper intervention. The pathway is currently being used in candidates for spinal fusion surgery to optimize their bone health prior to and following surgery. With a patient’s bone health critical to the success of a spine fusion, the clinical protocol calls for a preoperative evaluation of bone health using bone density and laboratory tests. Based on the results, a treatment plan is developed with the goal of maximizing bone quality to ensure the best surgical outcomes. Clinicians and scientists with expertise in metabolic bone disease and orthopaedic bone health conduct research that crosses basic, clinical, and translational platforms with the common focus on preservation of bone quality. Current investigations at HSS concentrate on bone biology, chemistry, and the mechanics of bone growth, including how to harness the natural healing power of bone to prevent fracture and treat diseased bone.

Linda A. Russell, MD Director

Perioperative bone health is an important focus of both clinical and research endeavors, and key to efforts to improve bone quality is the Hospital’s Osteoporosis Center of Excellence – a state-of-the-art testing, diagnostic, and education facility – and one of only 14 centers nationwide to be accredited by the International Society of Clinical Densitometry. The Center recently recruited a nurse practitioner who will be expanding the Center’s practice and initiatives in bone health.

Linda A. Russell, MD, and colleagues recently completed a study on osteoporosis drug therapy strategies in the setting of diseasemodifying agents for autoimmune disease. Their systematic review of the clinical literature evaluated the effects of methotrexate (MTX) and tumor necrosis factor-alpha (TNF-α) inhibitors on bone mineral properties as described in case reports, populationbased, cohort, and case controlled studies, and randomized controlled trials. It appears that MTX and TNF-α inhibitors do not have an adverse effect on bone mineral density (MBD) in patients with inflammatory disease. Their negative effects on BMD and bone turnover in pre-clinical models appear to be outweighed by their anti-disease effects in clinical studies. Based on the review, the researchers suggested a rational drug therapy strategy for treating osteoporosis in patients with inflammatory disease, and future studies will focus on developing optimal drug strategies when combining disease modifying anti-rheumatic drugs with anti-osteoporotic agents in this patient population. ■

Center of Excellence: Pediatric Rheumatology

professional staff

Thomas J.A. Lehman, MD, FAAP Chief Alexa B. Adams, MD Laura Barinstein, MD Theresa T. Lu, MD, PhD supported by St. Giles Research Chair Nancy Pan, MD Allied Health Professional Lydia Vazquez, LCSW

The Division of Pediatric Rheumatology continues to provide the full range of advanced treatments for children with complex rheumatic diseases. HSS has been at the forefront of defining optimal use of biologic therapies in children with rheumatic diseases. Innovative treatment approaches developed at the Hospital include the combination therapy of rituximab and cytoxan in systemic lupus erythematosus (SLE). Thomas J.A. Lehman, MD, and his colleagues have now completed a fiveThomas J.A. Lehman, MD, FAAP year follow-up study on children with SLE aggressively treated with this therapy with dramatic results showing that they are virtually disease-free. Most recently, Dr. Lehman, Nancy Pan, MD, and their colleagues reported on their study of patterns and influence of familial autoimmunity in pediatric SLE. A high prevalence of autoimmune disease has been documented in relatives of adult patients with SLE, however, data on familial inheritance patterns in pediatric SLE patients are scarce. In a retrospective chart review of 69 patients with pediatric-onset SLE, the researchers found that the most common diseases in relatives of children with SLE were SLE (21 percent) and thyroid disease (15 percent). Children presenting with SLE at an earlier age, as well as those with no family history of autoimmune disease, were more likely to have severe SLE, although severity did not differ by gender. They conclude that larger studies are necessary to elucidate patterns of familial inheritance and baseline patient characteristics that may affect severity of disease in pediatric SLE. Dr. Lehman continues as a principal investigator of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, a network of pediatric rheumatology research centers across North America.

Nancy Pan, MD

In 2012, Dr. Nancy Pan, a former fellow in pediatric rheumatology at HSS, joined the Division. Dr. Pan received her medical degree from New York University School of Medicine and completed her residency in pediatrics at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. During her fellowship, Dr. Pan pursued clinical and translational research identifying biomarkers for flares in lupus under the mentorship of Kyriakos A. Kirou, MD, Co-Director of the Mary Kirkland Center for Lupus Care. â&#x2013;

Division of Rheumatology

Professional Staff

DEPARTMENT OF MEDICINE Physician-in-Chief, Director of Medicine, and Chief, Rheumatology Division Mary K. Crow, MD Perioperative Medicine Division Linda A. Russell, MD Director Rheumatology Faculty Practices Theodore R. Fields, MD, FACP Coordinator Rheumatology Fellowship Program Anne R. Bass, MD, FACP Director Jessica R. Berman, MD Associate Director Thomas J.A. Lehman, MD, FAAP Director, Pediatric Rheumatology Fellowship Program Alexa B. Adams, MD Associate Director, Pediatric Rheumatology Fellowship Program Academy of Rheumatology Medical Educators Stephen A. Paget, MD, FACP, MACR Director Jessica R. Berman, MD Associate Director Physician-in-Chief Emeriti Charles L. Christian, MD, MACR Stephen A. Paget, MD, FACP, MACR Physicians Emeriti Lawrence J. Kagen, MD, MACR Irwin Nydick, MD Ernest Schwartz, MD Attending Physicians Richard S. Bockman, MD, PhD (Endocrinology) Barry D. Brause, MD, FACP Chief, Infectious Disease Mary K. Crow, MD Physician-in-Chief Theodore R. Fields, MD, FACP Allan Gibofsky, MD, JD, DACP, FCLM Lionel B. Ivashkiv, MD Thomas J.A. Lehman, MD, FAAP Chief, Pediatric Rheumatology Michael D. Lockshin, MD, MACR Steven K. Magid, MD Joseph A. Markenson, MD, FACP, MACR

Division of Rheumatology

Stephen A. Paget, MD, FACP, MACR Francis Perrone, MD (Cardiovascular Disease) Jane E. Salmon, MD James P. Smith, MD (Pulmonary Medicine) Harry Spiera, MD Associate Attending Physicians Anne R. Bass, MD, FACP Jessica R. Berman, MD Harry Bienenstock, MD Lisa R. Callahan, MD (Primary Care Sports Medicine) Doruk Erkan, MD, MPH Brian C. Halpern, MD Chief, Primary Care Sports Medicine C. Ronald MacKenzie, MD Carol A. Mancuso, MD, FACP Jordan D. Metzl, MD (Primary Care Sports Medicine) Martin Nydick, MD (Endocrinology) Lisa R. Sammaritano, MD Sergio Schwartzman, MD Robert F. Spiera, MD Richard Stern, MD Mary Beth Walsh, MD Assistant Attending Physicians Alexa B. Adams, MD (Pediatric Rheumatology) Juliet B. Aizer, MD, MPH Dalit Ashany, MD Laura V. Barinstein, MD (Pediatric Rheumatology) John W. Barnhill, MD Chief, Psychiatry Service Samantha K. Brenner, MD, MPH (Perioperative Medicine) William W. Briner, Jr. MD (Primary Care Sports Medicine) Matthew L. Buchalter, MD (Perioperative Medicine) Trang M. Bui, MD, MPH (Perioperative Medicine) Vivian P. Bykerk, MD, FRCPC James J. Calloway III, MD (Perioperative Medicine) Hyun Susan Cha, MD (Pediatrics) Gina DelGiudice, MD Stephen J. Di Martino, MD, PhD Timothy C. Dutta, MD (Cardiology)

Obi Eneanya, MD (Perioperative Medicine) Jacobo Futran, MD Flavia A. Golden, MD Susan M. Goodman, MD Marci A. Goolsby, MD (Primary Care Sports Medicine) Jessica K. Gordon, MD Wesley Hollomon, MD (Perioperative Medicine) Lisa S. Ipp, MD Chief, Pediatrics Michael I. Jacobs, MD (Dermatology) James J. Kinderknecht, MD (Primary Care Sports Medicine) Osric S. King, MD (Primary Care Sports Medicine) Kyriakos A. Kirou, MD, DSc, FACP Mary J. Kollakuzhiyil, MD (Perioperative Medicine) Lawrence F. Levin, MD Chief, Cardiology Lisa A. Mandl, MD, MPH Charis F. Meng, MD Andrew O. Miller, MD (Infectious Disease) Marissa D. Newman, MD (Perioperative Medicine) Dana E. Orange, MD Nancy Pan, MD (Pediatric Rheumatology) Sonal S. Parr, MD (Perioperative Medicine) Edward J. Parrish, MD Stephanie L. Perlman, MD (Pediatrics) Jill M. Rieger, MD (Perioperative Medicine) Linda A. Russell, MD Director, Perioperative Medicine Magdalena E. Swierczewski, MD (Perioperative Medicine) Ariel D. Teitel, MD Lisa C. Vasanth, MD, MS Hendricks H. Whitman III, MD Arthur M.F. Yee, MD, PhD Christine Yu, MD (Perioperative Medicine) Christine M. Yu, MD (Perioperative Medicine) Florence Yu, MD (Perioperative Medicine)

Professional Staff

Instructor in Medicine George D. Kalliolias, MD, PhD Physicians to the Ambulatory Care Center Bento R. Mascarenhas, MD Lakshmi Nandini Moorthy, MD (Pediatric Rheumatology) Alana C. Serota, MD Dee Dee Wu, MD David A. Zackson, MD Fellows in Rheumatic Disease Elana J. Bernstein, MD Soumya Chakravarty, MD, PhD Reena Khianey, MD Susan Kim, MD Lindsay Lally, MD Alana Levine, MD Konstaninos Loupasakis, MD Sonali Narain, MD

Danielle Ramsden-Stein, MD Lauren Wong, MD Weijia Yuan, MD Fellows in Pediatric Rheumatology Cassyanne Agular, MD Rose Karanicola, MD Christina Mertelsmann-Voss, MD Heather Walters, MD research division Leadership Steven R. Goldring, MD, MACR Chief Scientific Officer Lionel B. Ivashkiv, MD Associate Chief Scientific Officer and Director of Basic Research

Senior Scientists Carl P. Blobel, MD, PhD Adele L. Boskey, PhD Mary K. Crow, MD Mary B. Goldring, PhD Lionel B. Ivashkiv, MD Alessandra B. Pernis, MD Jane E. Salmon, MD Peter A. Torzilli, PhD Associate Scientists Theresa T. Lu, MD, PhD Carol Mancuso, MD Inez Rogatsky, PhD Assistant Scientists Qiu Guo, PhD Xiaoyu Hu, MD, PhD Kyriakos A. Kirou, MD, DSc, FACP

Robert N. Hotchkiss, MD Director of Clinical Research

ENDOWED CHAIRS, PROFESSORSHIPS, AND FELLOWSHIPS

Endowed chairs, professorships, and fellowships recognize the generosity of our donors and sustain excellence in rheumatology care, research, and medical education. Named Chairs and professorships Franchellie M. Cadwell Chair Sergio Schwartzman, MD Collette Kean Research Chair Jane E. Salmon, MD David H. Koch Chair for Arthritis and Tissue Degeneration Research Lionel B. Ivashkiv, MD C. Ronald MacKenzie, MD, Chair in Ethics and Medicine supporting the work of Wayne N. Shelton, PhD, and Stephanie M. Vertrees, MD Richard L. Menschel Research Chair Steven R. Goldring, MD, MACR

Stephen A. Paget, MD, Chair in Rheumatology Stephen A. Paget, MD Benjamin M. Rosen Chair in Immunology and Inflammation Research Mary K. Crow, MD Joseph P. Routh Professor of Rheumatic Diseases in Medicine Mary K. Crow, MD Virginia F. and William R. Salomon Chair in Musculoskeletal Research Carl P. Blobel, MD, PhD Peter Jay Sharp Chair in Lupus Research Alessandra B. Pernis, MD St. Giles Research Chair supporting Theresa T. Lu, MD, PhD

Robert and Gillian Steel Fellowship in Musculoskeletal Research Inez Rogatsky, PhD Russell F. Warren, MD, Research Chair supporting Suzanne A. Maher, PhD Named fellowships Charles L. Christian, MD, Research Fellowship Lisa Mandl, MD, MPH Ira W. DeCamp Fellowship in Musculoskeletal Genetics Mary B. Goldring, PhD Immunology and Inflammation Fellowship Sergei Rudchenko, PhD

Division of Rheumatology

2011-2012 NOTABLE ACHIEVEMENTS

Rheumatologists at HSS are regularly cited for their professional achievements and outstanding contributions to patient care, research, and education. They hold leadership positions and are on numerous committees of national and international organizations and professional societies, and serve as editors and on editorial boards of the major peerreviewed journals in the field. Awards and Special Recognition Alexa B. Adams, MD “My Doc Rocks” Award, Arthritis Foundation Juliet B. Aizer, MD, MPH Innovative Education Grant, Academy of Medical Educators, Hospital for Special Surgery Clinician Scholar Educator Award, American College of Rheumatology Research and Education Foundation Anne R. Bass, MD, FACP Invited Speaker, Update in Rheumatology, April 2012 Annual Meeting, American College of Physicians, New Orleans Elana J. Bernstein, MD Distinguished Fellow Award, American College of Rheumatology Clinical to Research Transition Award, Arthritis Foundation KL2 Post-Doctoral Scholar Award, Clinical and Translational Science Center, Weill Cornell Medical College Research Travel Grant, European Workshop for Rheumatology Invited Speaker, “Hypophosphatemia is Associated with Nephrogenic Systemic Fibrosis: A Case-Control Study,” 32nd European Workshop for Rheumatology Research, Stockholm, Sweden Carl P. Blobel, MD, PhD Invited Speaker: International Vascular Biology Meeting, Wiesbaden, Germany; “Protease World in Health and Disease,” Kiel International Symposium, Berlin, Germany; Catholic University in Santiago de Chile; Keynote Lecture, Gordon Research Conference Research Award, “ADAMs: Key Regulators of EGFR Signaling,” National Institutes of Health/National Institute of General Medical Sciences

Richard S. Bockman, MD, PhD Invited Speaker: “Efficacy and Safety of Calcium Supplementation,” National Meeting, American College of Rheumatology; Debate the Pro of Calcium (Con – Ian Reid), Advances in Mineral Metabolism Meeting; “When to Stop/ When to Restart Osteoporosis Therapy,” Premier Symposium, National Endocrine Society Soumya D. Chakravarty, MD, PhD Rheumatology Scientist Development Award, American College of Rheumatology Research and Education Foundation Mary K. Crow, MD Invited Participant, Annual Intramural Retreat, National Institute of Arthritis and Musculoskeletal and Skin Diseases Visiting Professor, Annual Rheumatology Research Day, University of Pennsylvania Medical School Visiting Professor, University of Pittsburgh School of Medicine Lecturer, United States Bone and Joint Initiative, Value in Musculoskeletal Care Conference Doruk Erkan, MD, MPH Invited Speaker: APS ACTION, NIH Roundtable on APS, National Institutes of Health Office of Rare Disease Research; “Management of Antiphospholipid Syndrome,” 12th National Turkish Rheumatology Meeting, Antalya, Turkey Allan Gibofsky, MD, JD, DACP, FCLM Ali Askari Endowed Lectureship, Case Western Reserve University School of Medicine Invited Speaker: UCLA, Division of Rheumatology; University of Kentucky, Division of Rheumatology; Cleveland Clinic, Division of Rheumatology Mary B. Goldring, PhD Invited Speaker: Advances in Mineral Metabolism Meeting, Aspen, CO; Joint Meeting of the Bone Research Society and British Orthopedic Research Society, Cambridge, United Kingdom Steven R. Goldring, MD, MACR Visiting Scientist, Annual Orthopaedic Research Day, University of Pennsylvania Medical School Invited Speaker: Targeted Therapies Meeting, Baveno, Italy; Advances in Mineral Metabolism Meeting, Aspen, CO; Osteoarthritis Research Society International Meeting, Barcelona, Spain; 2nd Asia-Pacific Osteoporosis and Bone Meeting, Brisbane, Australia; Scientific Symposium, University of Pennsylvania Penn Center for Musculoskeletal Disorders

Division of Rheumatology

Jessica K. Gordon, MD New Investigator Award, Scleroderma Foundation Clinician Scientist Career Development Award, Hospital for Special Surgery Qiu Guo, PhD Research Award, Feldstein Medical Foundation Lionel B. Ivashkiv, PhD Invited Speaker, “Notch Signaling and Toll-like Receptors in Arthritis,” Sun Valley Workshop on Musculoskeletal Biology, International Bone & Mineral Society Michael D. Lockshin, MD, MACR National Leadership Award for Lupus Medical Advancement, Lupus Foundation of America Invited Speaker: 7th International Conference on Sex Hormones, Pregnancy, and Rheumatic Diseases, Italy; 8th Meeting of the European Forum on Antiphospholipid Antibodies; Istituto Auxologico Italiano Ospedale Theresa T. Lu, MD, PhD Novel Research Grant Award to study the “Mechanism of UV-Induced Skin Inflammation,” Lupus Research Institute Invited Speaker: “Regulating Lymph Node Vascular-Stromal Growth,” Annual Meeting Plenary Session on Stromal Cells, American Association of Immunologists; “Fibroblast Regulation by Dendritic Cells,” Basic Science Plenary Session on Fibrosis, American College of Rheumatology Suzanne A. Maher, PhD 2012 BioAccelerate NYC Prize for “A Novel Hydrogel for Focal Cartilage Defect Repair” Keynote Speaker, International Symposium on Arthroscopic Cartilage Surgery and Related Research, Arthroscopy and Knee Society, Taiwan Kyung-Hyun Park-Min, PhD Pathway to Independence Award to study “Negative Regulation of Osteoclastogenesis by Inflammatory Signals,” National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Alessandra B. Pernis, MD Research Grant to study “Effector Tregs in Lupus,” National Institutes of Health/National Institute of Allergy and Infectious Diseases Invited Speaker: Juvenile Diabetes Research Center Meeting, Harvard Medical School; Fourth Annual Symposium on Systemic Lupus Erythematosus, Beth Israel Deaconess Medical Center; “Sex, Pregnancy, and Autoimmunity Through the Lifespan,” Clinical Immunology Society Linda A. Russell, MD 2012 Honoree, Women on the Move, Arthritis Foundation, New York Chapter

Jane E. Salmon, MD Virginia Kneeland Frantz ’22 Distinguished Women in Medicine Award, Columbia University College of Physicians and Surgeons Alumni Association Visiting Professor, Annual Ogryzlo Research Day, Division of Rheumatology, University of Toronto 35th Annual Michael Einbender Distinguished Lectureship, University of Missouri School of Medicine Baohong Zhao, PhD Harold M. Frost Young Investigator Award, American Society for Bone and Mineral Research Pathway to Independence Award to study “Regulation of Osteoclastogenesis and Arthritic Bone Resorption by RBP-J,” National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases LEADERSHIP POSITIONS Juliet B. Aizer, MD, MPH CARE 2012 Development Group, American College of Rheumatology Anne R. Bass, MD, FACP Rheumatology Section Author and Editor, Medical Knowledge Self-Assessment Program Chairman, Training Resources Subcommittee, Committee on Workforce and Training, American College of Rheumatology Member, Task Force (on timing of residency match), Association of American Medical Colleges Elana J. Bernstein, MD Member, Annual Meeting Planning Committee and Fellows Subcommittee, American College of Rheumatology Carl P. Blobel, MD, PhD Chair, Basic and Translational Science Session, “Meet the ADAM’s Family: ADAM, MMP’s, ADAMTS,” The European League Against Rheumatism, Berlin, Germany Richard S. Bockman, MD, PhD Chair, Calcium Subcommittee of Professional Practice Committee, American Society of Bone and Mineral Research Steering and Planning Committee for Clinical Endocrine Update Course, Endocrine Society Scientific Advisory Committee, Women’s Health Bone Specialist, U.S. Food and Drug Administration Clinical Research Subcommittee on Steering Committee for Symposium on “Engaging Basic Scientists in Translational Research,” Federation of American Societies for Experimental Biology

Division of Rheumatology

2011-2012 NOTABLE ACHIEVEMENTS

Theresa T. Lu, MD, PhD Charter Member, Atherosclerosis and Inflammation of the Cardiovascular System Study Section, National Institutes of Health Section Juvenile Arthritis Research Task Force, Arthritis Foundation

Doruk Erkan, MD, MPH Executive Committee Chair, Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Meeting Organizer: 2nd APS ACTION Annual Summit, Chicago; 2nd APS ACTION Working Meeting, Berlin, Germany; 3rd APS ACTION Annual Summit, Washington, DC

Jane E. Salmon, MD Scientific Advisory Board, Alliance for Lupus Research Council Member, Henry Kunkel Society

Theodore R. Fields, MD, FACP Medical Advisor, Men’s Health Network, Washington, DC Abstract Selection Committee, Abstracts for 2011 Annual Meeting: Quality Measures and Innovations in Practice Management and Care Delivery, American College of Rheumatology Allan Gibofsky, MD, JD, DACP, FCLM Vice President, Consortium of Rheumatology Researchers of North America Special Consultant, U.S. Food and Drug Administration Mary B. Goldring, PhD Chair, “Cartilage Degeneration and Repair in OA,” Sun Valley Workshop on Musculoskeletal Biology, International Bone & Mineral Society Review Panel, United Kingdom “Centre of Excellence: Pathogenesis of Osteoarthritis” Program Grants Steven R. Goldring, MD, MACR Co-Chair, Annual Meeting Basic Research Conference, American College of Rheumatology Advisory and Organizing Committee and Session Chair, Sun Valley Workshop on Musculoskeletal Biology, International Bone & Mineral Society Review Panel, United Kingdom “Centre of Excellence: Pathogenesis of Osteoarthritis” Program Grants Jessica K. Gordon, MD Medical Advisory Board, Scleroderma Foundation, Tri-State Chapter Xiaoyu Hu, MD, PhD Ad Hoc Member, National Institutes of Health Atherosclerosis and Inflammation in Cardiovascular Systems Study Section

Joseph M. Lane, MD Chair, Special Grants Review Committee Study Section, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Mary K. Crow, MD Chair, Scientific Advisory Board, Alliance for Lupus Research Member, Scientific Advisory Board, Arthritis National Research Foundation Member, Board of Trustees, Arthritis Foundation, New York Chapter Chair, Alliance for Lupus Research Annual Investigators’ Scientific Meeting Member, Arthritis, Connective Tissue and Skin Study Section, NIH Co-Chair, Centers of Research Translation Study Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Division of Rheumatology

Carol A. Mancuso, MD Reviewer, Special Emphasis Panel Study Section, Clinical Trial Pilot Studies, and Study Section, Research Dissemination and Implementation Proposals, National Institutes of Health/National Heart, Lung, and Blood Institute

Robert F. Spiera, MD Medical Consultant and Member, Scientific Advisory Board, Vasculitis Foundation Chairman, Medical and Scientific Advisory Board, Scleroderma Foundation, Tri-State Chapter EDITORIAL APPOINTMENTS Juliet B. Aizer, MD, MPH Editorial Board, Current Reviews in Musculoskeletal Medicine Mary K. Crow, MD Associate Editor, Annals of the Rheumatic Diseases Editorial Board: Annual Review of Medicine; Arthritis Research and Therapy; Current Opinion in Rheumatology Theodore R. Fields, MD, FACP Advisory Editor, Arthritis & Rheumatism Steven R. Goldring, MD, MACR Co-Editor, Bone, August 2012 issue focused on osteoarthritis Susan M. Goodman, MD Associate Editor, Clinical Decision Support: Rheumatology Section Editor, Current Rheumatology Reports C. Ronald MacKenzie, MD Deputy Editor, HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery Jane E. Salmon, MD Associate Editor, Annals of the Rheumatic Diseases Theresa T. Lu, MD, PhD Editorial Board, Faculty 1000 Research Reviewer, Faculty 1000, Immune Response Section Review Editorial Board, Frontiers in Molecular Antigen Presenting Cell Biology

2011-2012 Selected publications

Peer-Reviewed Journals Aizer JB. Roughness. Annals of Internal Medicine. 2012;157(3):216. Aizer JB. Apologies. Annals of Internal Medicine. 2012 Oct 16;157(8):596. Andrade D, Redecha PB, Vukelic M, Qing X, Perino G, Salmon JE, Koo GC. Engraftment of PBMC from SLE and APS donors into BALB-Rag2-/-IL2Rgc-/-mice: a promising model for studying human disease. Arthritis & Rheumatism. 2011 63: 2764-73. Baird EM, Lehman TJ, Worgall S. Combination therapy with rituximab and cyclophosphamide in the treatment of anti-neutrophil cytoplasmic antibodies (ANCA) positive pulmonary hemorrhage: case report. Pediatric Rheumatology Online Journal. 2011 Oct 27;9(1):33. Baker N, Sharpe P, Culley K, Otero M, Bevan D, Newham P, Barker W, Clements KM, Langham CJ, Goldring MB, Gavrilovic J. Dual regulation of metalloproteinase expression in chondrocytes by Wnt-1-inducible signaling pathway protein 3/CCN6. Arthritis & Rheumatism. 2012 Jul;64(7):2289-99. Bartlett SJ, Hewlett S, Bingham III CO, Woodworth TG, Alten R, Pohl C, Choy EH, Sanderson T, Boonen A, Bykerk VP, Leong AL, Strand V, Furst DE, Christensen R. Identifying core domains to assess flare in rheumatoid arthritis: an OMERACT International Patient and Provider Combined Delphi Consensus. Annals of the Rheumatic Diseases. 2012 Nov;71(11):1855-1860. Benahmed F, Ely S, Lu TT. Lymph node vascular-stromal growth and function as a potential target for controlling immunity. Clinical Immunology. 2012 Aug;144(2):109-16. Benahmed F, Lu TT. Invited Federation of Clinical Immunology Societies (FOCIS) review: regulating lymph node vascularstromal growth and function to regulate immunity. Clinical Immunology. 2012 144:109-116. Berman JR, Aizer J, Bass AR, Cats-Baril WL, Parrish EJ, Robbins L, Salmon JE, Paget SA. Building a rheumatology education academy: insights from assessment of needs during a rheumatology division retreat. The Journal of Rheumatology. 2012 Jun;39(6):1280-86. Berman JR, Aizer J, Bass AR, Cats-Baril WL, Parrish EJ, Robbins L, Salmon JE, Paget SA. Creating an academy of medical educators: how and where to start? HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery. 2012 Jul;8(2):165-68.

Berman JR, Ben-Artzi A, Fisher MC, Bass AR, Pillinger MH. A comparison of arthrocentesis teaching tools: cadavers, synthetic joint models, and the relative utility of different educational modalities in improving trainees’ comfort with procedures. Journal of Clinical Rheumatology. 2012 Jun;18(4):175-79. Bernstein E, Kay J, Gibofsky A. Treating rheumatoid arthritis to target: an international initiative. Current Reviews in Musculoskeletal Medicine. 2011 Sep;4(3):79-83. Bernstein EJ, Kay J, Gibofsky A. Erratum to: Treating rheumatoid arthritis to target: an international initiative. Current Reviews in Musculoskeletal Medicine. 2011 Sep;4(3):157. Bernstein EJ, Schmidt-Lauber C, Kay J. Nephrogenic systemic fibrosis: a systemic fibrosing disease resulting from gadolinium exposure. Best Practice & Research: Clinical Rheumatology. 2012. Aug;26(4):489-503. Bildaci YD, Erkan D. Catastrophic antiphospholipid syndrome: diagnostic difficulties and updated diagnostic algorithms. RAED Journal. 2012. In press. Bingham CO, Alten R, Bartlett SJ, Bykerk VP, Brooks PM, Choy E, et al. Identifying preliminary domains to detect and measure rheumatoid arthritis flares: report of the OMERACT 10 RA Flare Workshop for the OMERACT RA Flare Definition Working Group. The Journal of Rheumatology. Aug 2011 38(8):1751-58. Biswas PS, Gupta S, Stirzaker RA, Kumar V, Jessberger R, Lu TT, Bhagat G, Pernis AB. Dual regulation of IRF4 function in T and B cells is required for the coordination of T-B cell interactions and the prevention of autoimmunity. Journal of Experimental Medicine. 2012 Mar 12;209(3):581-96. Bockman RS, Zapalowski C, Kiel DP, Adler RA. Commentary on calcium supplements and cardiovascular events. Journal of Clinical Densitometry. 2012 Apr-Jun;15(2):130-34. Bombardier C, Hazlewood GS, Akhaven P, Schieir O, Dooley A, Haraoui B, Khraishi M, LeClercq SA, Légaré J, Mosher DP, Pencharz J, Pope JE, Thomson J, Thorne C, Zummer M, Gardam MA, Askling J, Bykerk V. Canadian Rheumatology Association (CRA) recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease modifying anti-rheumatic drugs: part II safety. The Journal of Rheumatology. 2012 Aug;39(8):1583-602. Branch W; Obstetric Task Force. Report of the Obstetric APS Task Force: 13th International Congress on Antiphospholipid Antibodies, 13th April 2010. Lupus. 2011 Feb;20(2):158-64.

Division of Rheumatology

2011-2012 Selected publications

Burton L, Paget D, Binder NB, Bohnert K, Nestor BJ, Sculco TP, Santambrogio L, Ross FP, Goldring SR, Purdue PE. Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation. Journal of Orthopaedic Research. 2012 Aug 29. Epub ahead of print. Bykerk VP, Hazelwood G, Akhavan P, et al. The Canadian Rheumatology Association (CRA) Guidelines for the Pharmacologic Management of Rheumatoid Arthritis – Treatment and Efficacy. The Journal of Rheumatology. Epub online 2011; 38:11. Bykerk VP, Jamal S, Boire G, Hitchon C, Pope JE, Thorne JC, Sun Y, Keystone EC, CATCH Investigators. The Canadian Early Arthritis Cohort (CATCH): patients with new onset synovitis meeting the 2010 ACR/EULAR Classification Criteria but not the 1987 ACR Classification Criteria present with less severe disease activity. The Journal of Rheumatology. 2012. Epub ahead of print. Bykerk VP, Östör AJK, Alvaro-Gracia J, Pavelka K, Ivorra JAR, Graninger W, Bensen W, Nurmohamed MT, Krause A, Bernasconi C, Stancati A, Sibilia J. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Annals of the Rheumatic Diseases. 2012 July 6. Epub ahead of print. Bykerk VP, Schieir O, Akhavan P, Hazlewood GS, Cheng CK, Bombardier C. Emerging issues in pharmacological management of rheumatoid arthritis: results of a national needs assessment survey identifying practice variations for the development of Canadian Rheumatology Association Clinical Practice Recommendations. The Journal of Rheumatology. 2012 Aug;39(8):1555-58. Carmel AS, Shieh A, Bang H, Bockman RS. The 25(OH)D level needed to maintain a favorable bisphosphonate response is ≥33 ng/ml. Osteoporosis International. Oct;23(10):2479-87. Chakravarty SD, Harris ME, Schreiner AM, Crow MK. Sarcoidosis triggered by interferon-Beta treatment of multiple sclerosis: a case report and focused literature review. Seminars in Arthritis and Rheumatism. 2012 Oct; 42(2):206-12. Chakravarty SD, Yee AF, Paget SA. Rituximab successfully treats refractory chronic autoimmune urticaria caused by IgE receptor autoantibodies. Journal of Allergy and Clinical Immunology. 2011 Dec;128(6):1354-55. Chen S, Lee Y, Crother TR, Fishbein M, Zhang W, Yilmaz A, Shimada K, Schulte DJ, Lehman TJ, Shah PK, Arditi M. Marked acceleration of atherosclerosis after Lactobacillus

Division of Rheumatology

casei-induced coronary arteritis in a mouse model of Kawasaki disease. Arteriosclerosis, Thrombosis and Vascular Biology. 2012 Aug;32(8):e60-71. Chung SA, Xie G, Roshandel D, Sherva R, Edberg JC, Kravitz M, Dellaripa PF, Hoffman GS, Mahr AD, Seo P, Specks U, Spiera RF, St Clair EW, Stone JH, Plenge RM, Siminovitch KA, Merkel PA, Monach PA. Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener’s) reveals shared susceptibility loci with rheumatoid arthritis. Arthritis & Rheumatism. 2012 Oct;64(10):3463-71. Chyou S, Benahmed F, Tian S, Chen J, Kumar V, Lipp M, Lu TT. Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells. Journal of Immunology. 2011 Dec 1;187(11):5558-67. Chyou S, Tian S, Ekland EH, Lu TT. Normalization of the lymph node T cell stromal microenvironment in lpr/lpr mice is associated with SU5416-induced reduction in autoantibodies. PLoS One. 2012;7(3):e32828. Clowse ME, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, Spiera RF, Davis JC Jr, McCune WJ, Ytterberg SR, St Clair EW, Allen NB, Specks U, Stone JH; WGET Research Group. Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener’s). Arthritis Care & Research (Hoboken). 2011 Dec;63(12):1777-81. Cohen D, Colvin R, Daha M, Drachenberg C, Haas M, Nickeleit V, Salmon JE, Sis B, Zhao M, Bruijn JA, Bajema I. C4d as a biomarker in transplantation, autoimmunity and pregnancy. Kidney International. 2012 81:628-39. Day MS, Nam D, Goodman S, Su EP, Figgie M. Psoriatic arthritis. Journal of the American Academy of Orthopaedic Surgeons. 2012 Jan;20(1):28-37. Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, Lorich DG, Lane JM, Boskey AL. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. Journal of Bone and Mineral Research. 2012 Mar;27(3):672-78. Donnelly E, Saleh A, Unnanuntana A, Lane JM. Atypical femoral fractures: epidemiology, etiology, and patient management. Current Opinion in Supportive and Palliative Care. 2012 Sep;6(3):348-54. Dragomir CL, Scott JL, Perino G, Adler R, Fealy S, Goldring MB. Acute inflammation with induction of anaphylatoxin C5a and terminal complement complex C5b-9 associated with multiple intra-articular injections of hylan G-F 20: a case report. Osteoarthritis Cartilage. 2012 Jul;20(7):791-95.

Dwivedi N, Upadhyay J, Neeli I, Khan S, Pattanaik D, Myers L, Kirou KA, Hellmich B, Knuckley B, Thompson PR, Crow MK, Mikuls TR, Csernok E, Radic M. Felty’s syndrome autoantibodies bind to deiminated histones and neutrophil extracellular chromatin traps. Arthritis & Rheumatism. 2012;64(4):982-92. Dy CJ, Dossous PM, Ton QV, Hollenberg JP, Lorich DG, Lane JM. Does a multidisciplinary team decrease complications in male patients with hip fractures? Clinical Orthopaedics and Related Research. 2011 Jul;469(7):1919-24. Dy CJ, Dossous PM, Ton QV, Hollenberg JP, Lorich DG, Lane JM. The medical orthopaedic trauma service: an innovative multidisciplinary team model that decreases in-hospital complications in patients with hip fractures. Journal of Orthopaedic Trauma. 2012 Jun;26(6):379-83. Dy CJ, Lamont LE, Ton QV, Lane JM. Sex and gender considerations in male patients with osteoporosis. Clinical Orthopaedics and Related Research. 2011 Jul;469(7):1906-12. Dy CJ, McCollister KE, Lubarsky DA, Lane JM. An economic evaluation of a systems-based strategy to expedite surgical treatment of hip fractures. The Journal of Bone & Joint Surgery (Am). 2011 Jul 20;93(14):1326-34. Erkan D, Derksen R, Levy R, Machin S, Ortel T, Pierangeli S, Roubey R, Lockshin MD. Antiphospholipid Syndrome Clinical Research Task Force report. Lupus. 2011 Feb;20(2): 219-24. Erkan D, Lockshin MD. High-risk antiphospholipid antibody profile: matter of the number or titer of tests? E-Letter to the Editor (re: Incidence of first thrombembolic event in asymptomatic carries of high-risk aPL profile: a multicenter prospective study, Pengo et al). Blood. 2011;17:4714. Published online on January 24, 2012. Erkan D, Lockshin MD, on behalf of APS ACTION members. Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking. Lupus. 2012;21(7):695-98. Erkan D, Vega J, Ramon G, Kozora E, Lockshin MD. Rituximab in antiphospholipid syndrome (RITAPS): a pilot open-label phase II prospective trial for non-criteria manifestations of antiphospholipid antibodies. Arthritis & Rheumatism. 2012. In press. Fabricant PD, Unnanuntana A, Hartman BJ, Lane JM. Multi-focal osteomyelitis with Streptococcus pneumoniae in a patient with Waldenström macroglobulinemia: a case report. The Journal of Bone & Joint Surgery (Am). 2011 May 4;93(9):e46. Forbess LJ, Bass AR. Update in rheumatology: evidence published in 2011. Annals of Internal Medicine. 2012 Jul 17; 157(2):114-19.

Forbess LJ, Fields TR. The broad spectrum of urate crystal deposition: unusual presentations of gouty tophi. Seminars in Arthritis & Rheumatism. 2012 Oct;42(2):146-54. Franzke CW, Cobzaru C, Triantafyllopoulou A, Löffek S, Horiuchi K, Threadgill DW, Kurz T, van Rooijen N, Bruckner-Tuderman L, Blobel CP. Epidermal ADAM17 maintains the skin barrier by regulating EGFR liganddependent terminal keratinocyte differentiation. The Journal of Experimental Medicine. 2012 Jun 4;209(6):1105-19. Ghomrawi HM, Franco Ferrando N, Mandl LA, Do H, Noor N, Gonzalez Della Valle A. How often are patient and surgeon recovery expectations for total joint arthroplasty aligned? Results of a pilot study. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery. 2011 Oct;7(3):229-34. Ghomrawi HM, Mancuso CA, Westrich GH, Marx RG, Mushlin AI; Expectations Discordance Study Group. Discordance in TKA expectations between patients and surgeons. Clinical Orthopaedics and Related Research. 2012 Jul 21. Epub ahead of print. Goldenberg D, Miller E, Perna M, Sattar N, Welsh P, Roman MJ, Salmon JE. N-terminal Pro-Brain Natriuretic Peptide is associated with cardiac but not vascular disease in systemic lupus erythematosus patients. Arthritis & Rheumatism. 2012 64:316-17. Goldring MB. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Therapeutic Advances in Musculoskeletal Disease. 2012 Aug;4(4):269-85. Goldring MB. Do mouse models reflect the diversity of osteoarthritis in humans? Arthritis & Rheumatism. 2012 Oct;64(10):3072-75. Goldring MB, Marcu KB. Epigenomic and microRNAmediated regulation in cartilage development, homeostasis, and osteoarthritis. Trends in Molecular Medicine. 2012 Feb;18(2):109-18. Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Therapeutic Advances in Musculoskeletal Disease. 2012 Aug;4(4):249-58. Goldring SR, Scanzello CR. Plasma proteins take their toll on the joint in osteoarthritis. Arthritis Research & Therapy. 2012 Mar 5;14(2):111. Goodman SM, Figgie MP, Mackenzie CR. Perioperative management of patients with connective tissue disease. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery. 2011 Feb;7(1):72-79.

Division of Rheumatology

2011-2012 Selected publications

Gordon RA, Grigoriev G, Lee A, Kalliolias GD, Ivashkiv LB. The interferon signature and STAT1 expression in rheumatoid arthritis synovial fluid macrophages are induced by tumor necrosis factor Îą and counter-regulated by the synovial fluid microenvironment. Arthritis & Rheumatism. 2012 Oct;64(10):3119-28.

Hobin JA, Deschamps AM, Bockman RS, Cohen S, Dechow P, Eng C, Galey W, Morris M, Prabhakar S, Raj U, Rubenstein P, Smith JA, Stover P, Sung N, Talman W, Galbraith R. Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles. Journal of Translational Medicine. 2012 Apr 13;10:72.

Gordon J, Spiera R. Tyrosine kinase inhibitors in the treatment of systemic sclerosis: the difficulty in interpreting proof-of-concept studies. International Journal of Rheumatology. 2011;2011:842181.

Huynh L, Wang L, Shi C, Park-Min KH, Ivashkiv LB. ITAM-coupled receptors inhibit IFNAR signaling and alter macrophage responses to TLR4 and Listeria monocytogenes. Journal of Immunology. 2012 Apr 1;188(7):3447-57.

Greenberg JD, Reed G, Decktor D, Harrold L, Furst D, Gibofsky A, Dehoratius R, Kishimoto M, Kremer JM; CORRONA Investigators. A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: results from the US CORRONA registry. Annals of the Rheumatic Diseases. 2012 Jul;71(7):1134-42.

Iuliana Shapira I, Andrade D, Allen SL, Salmon JE. Induction of durable remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis & Rheumatism. 2012 64:2719-23.

Gurion R, Lehman TJ, Moorthy LN. Systemic arthritis in children: a review of clinical presentation and treatment. International Journal of Inflammation. 2012;271569. Hall KC, Blobel CP. Interleukin-1 stimulates ADAM17 through a mechanism independent of its cytoplasmic domain or phosphorylation at threonine 735. PLoS One. 2012;7(2):e31600. Haraoui B, Bokarewa M, Kallmeyer I, Bykerk VP. Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an inadequate response to 1 prior tumor necrosis factor inhibitor: the RESET Trial. The Journal of Rheumatology. 2011 Dec;38(12):2548-56. Haraoui B, Smolen JS, Aletaha D, Breedveld FC, Burmester G, Codreanu C, Da Silva JP, de Wit M, Dougados M, Durez P, Emery P, Fonseca JE, Gibofsky A, Gomez-Reino J, Graninger W, Hamuryudan V, Jannaut PeĂąa MJ, Kalden J, Kvien TK, Laurindo I, Martin-Mola E, Montecucco C, Santos Moreno P, Pavelka K, Poor G, Cardiel MH, Stanislawska-Biernat E, Takeuchi T, van der Heijde D; Treat to Target Taskforce. Treating rheumatoid arthritis to target: multinational recommendations assessment questionnaire. Annals of the Rheumatic Diseases. 2011 Nov;70(11):1999-2002. Heuser CC, Eller AG, Warren J, Branch DW, Salmon J, Silver RM. A case-control study of membrane cofactor protein mutations in two populations of patients with early loss. Journal of Reproductive Immunology. 2011 91:71-75. Hirsch BP, Unnanuntana A, Cunningham ME, Lane JM. The effect of therapies for osteoporosis on spine fusion: a systematic review. The Spine Journal. 2012 Jun 1. Epub ahead of print.

Division of Rheumatology

Ivashkiv LB, Zhao B, Park-Min KH, Takami M. Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction of IRF8. Annals of the New York Academy of Sciences. 2011 Nov;1237:88-94. Jayasuriya CT, Goldring MB, Terek R, Chen Q. Matrilin-3 induction of IL-1 receptor antagonist is required for upregulating collagen II and aggrecan as well as down-regulating ADAMTS-5 gene expression. Arthritis Research & Therapy. 2012 Sep 11;14(5):R197. Epub ahead of print. Kalunian KC, Chatham WW, Massarotti EM, Reyes-Thomas J, Harris C, Furie RA, et al. Measurements of cell bound complement activation products enhance diagnostic performance in systemic lupus erythematosus. Arthritis & Rheumatism. 2012 Aug 29. Epub ahead of print. Kalliolias GD, Kirou KA. Type I interferons as biomarkers in autoimmune diseases. Biomarkers in Medicine. 2012;6(2): 137-40. Karsh J, Keystone EC, Haraoui B, Thorne JC, Pope J, Bykerk V, Maksymowych W, Zummer M, Bensen WG, Kraishi MM. Canadian Rheumatology Research Consortium. Canadian recommendations for clinical trials of pharmacologic interventions in rheumatoid arthritis: inclusion criteria and study design. The Journal of Rheumatology. 2011; 38:10. Katz JN, Chaisson CE, Cole B, Guermazi A, Hunter DJ, Jones M, Levy BA, Mandl LA, Martin S, Marx RG, Safran-Norton C, Roemer FW, Skoniecki D, Solomon DH, Spindler KP, Wright J, Wright RW, Losina E. The MeTeOR Trial (Meniscal Tear in Osteoarthritis Research): rationale and design features. Contemporary Clinical Trials. 2012 Nov;33(6): 1189-96.

Kelley JM, Monach PA, Ji C, Zhou Y, Wu J, Tanaka S, Mahr AD, Johnson S, McAlear C, Cuthbertson D, Carette S, Davis JC Jr, Dellaripa PF, Hoffman GS, Khalidi N, Langford CA, Seo P, St Clair EW, Specks U, Stone JH, Spiera RF, Ytterberg SR, Merkel PA, Edberg JC, Kimberly RP. IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic variants influences granulomatosis with polyangiitis. Proceedings of the National Academy of Sciences. 2011 Dec 20;108(51):20736-41. Kim S, Kirou K, Erkan D. Belimumab in systemic lupus erythematosus: an update for clinicians. Therapeutic Advances in Chronic Diseases. 2012;3:11-23. Kim SJ, Persad P, Erkan D, Kirou KA, Horton R, Salmon JE. Research studies and their implications for social work practice in a multidisciplinary center for lupus care. Social Work in Health Care. 2012;51(7):652-60. Kirou KA, Gkrouzman E, Chevalier JM, Seshan SV. Antiinflammatory strategies, not just B cell depletion, is required for optimal therapy of severe proliferative lupus nephritis. Comment on the article by Rovin et al. Arthritis & Rheumatism. 2012 Oct;64(10):3486. Kitchens CS, Erkan D, Brandao L, Hahn S, James AH, Kulkarni R, Pericak-Vance M, Vace J, Ortel TL. Thrombotic storm revisited: suggested diagnostic criteria and formation of the thrombotic storm study group. American Journal of Medicine. 2011;124(4):290-96. Kovacs E, Bykerk VP, Thorne JC, Hitchon CA, Boire G, Haraoui B, Keystone EC, Pope JE. Quality assurance study of the use of preventative therapies in glucocorticoid induced osteoporosis (GIOP) in early inflammatory arthritis: results from the CATCH cohort. Rheumatology (Oxford). 2012 Sep; 51(9):1662-69. Kozora E, Erkan D, West SG, Filley CM, Zhang L, Ramon G, Duggan E, Lockshin MD. Site differences in mild cognitive dysfunction among patients with SLE. Lupus. 2012. In press. Kronforst KD, Mancuso CJ, Pettengill M, Ninkovic J, Power Coombs MR, Stevens C, Otto M, Mallard C, Wang X, Goldmann D, Levy O. A neonatal model of intravenous staphylococcus epidermidis infection in mice <24 h old enables characterization of early innate immune responses. PLoS One. 2012;7(9). Kumar V, Chyou S, Stein JV, Lu TT. Optical projection tomography reveals dynamics of HEV growth after immunization with protein plus CFA and features shared with HEVs in acute autoinflammatory lymphadenopathy. Frontiers in Immunology. 2012;3:282.

Kuriya B, Sun Y, Boire G, Haraoui B, Hitchon C, Pope J, Thorne JC, Keystone EC, Bykerk VP, CATCH. Prevalence of remission in early RA: a comparison of new ACR/EULAR remission criteria to established criteria. The Journal of Rheumatology. 2012 Jun;39(6):1155-58. Lane JM. Bisphosphonate use for â&#x2030;Ľ5 years increased risk for subtrochanteric or femoral shaft fractures. The Journal of Bone & Joint Surgery (Am). 2011 Aug 17;93(16):1546. Lane JM. Osteoporosis and fracture risk. Orthopedics. 2011 May;34(5):370. Lee YC, Lu B, Boire G, Haraoui B, Hitchon CA, Pope JE, Thorne JC, Keystone EC, Ferland DS, Solomon DH, Bykerk VP, CATCH. Incidence and predictors of secondary fibromyalgia in an early arthritis cohort. Annals of the Rheumatic Diseases. 2012 July 11. Epub ahead of print. Lee Y, Schulte DJ, Shimada K, Chen S, Crother TR, Chiba N, Fishbein MC, Lehman TJ, Arditi M. Interleukin-1Î˛ is crucial for the induction of coronary artery inflammation in a mouse model of Kawasaki disease. Circulation. 2012 Mar 27;125(12):1542-50. Lehman TJ, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011 50(s5):v41-v48. Levine A, Erkan D. Clinical assessment and management of cytopenias in lupus patients. Current Rheumatology Reports. 2011;13(4):291-99. Lillegraven S, Prince FHM, Shadick N, Bykerk VP, Lu B, Frits ML, Iannaccone CK, Kvien TK, Haavardsholm EA, Weinblatt ME, Solomon DH. Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort. Annals of the Rheumatic Diseases. 2012 May;71(5):681-86. Lockshin MD. Antiphospholipid: to test, or not to test, that is the question. International Journal of Clinical Practice. 2012 Jul;66(7):620-21. Lockshin MD, Cohn E, Aslam A, Buyon JB, Salmon JE. Sex ratios of children of lupus pregnancies. Arthritis & Rheumatism. 2012 Oct 8. Epub ahead of print. Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis & Rheumatism. 2012 Jul;64(7):2311-18.

Division of Rheumatology

2011-2012 Selected publications

Lockshin MD, Salmon JE. Are posttranslational modifications of β2-glycoprotein I markers for thrombotic risk? Are they triggers of autoimmunity? Arthritis & Rheumatism. 2011 Sep;63(9):2558-60.

Manvelian G, Daniels S, Gibofsky A. A phase 2 study evaluating the efficacy and safety of a novel, proprietary, nano-formulated, lower dose oral diclofenac. Pain Medicine. 2012 Oct 8. Epub ahead of print.

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis & Rheumatism. 2012 Jun;64(6):1697-707.

McCarberg B, Gibofsky A. Need to develop new nonsteroidal anti-inflammatory drug formulations. Clinical Therapeutics. 2012 Sep;34(9):1954-63.

Lu TT. Dendritic cells: novel players in fibrosis and scleroderma. Current Rheumatology Reports. 2012 Feb;14(1):30-38.

McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science. 2012 Jan 13;335(6065):229-32.

Lu TT, Kim H, Ma X. IL-17, a new kid on the block of tertiary lymphoid organs. Cellular & Molecular Immunology. 2012 Jan;9(1):3-4. Lyman S, Oh LS, Reinhardt KR, Mandl LA, Katz JN, Levy BA, Marx RG. Surgical decision making for arthroscopic partial meniscectomy in patients aged over 40 years. Arthroscopy. 2012 Apr;28(4):492-501. Lynch AM, Eckel RH, Murphy JR, Gibbs RS, West NA, Giclas PC, Salmon JE, Holers VM. Prepregnancy obesity and complement system activation in early pregnancy and the subsequent development of preeclampsia. American Journal of Obstetrics & Gynecology. 2012 206: 428.e1-8. Mait JE, Perino G, Unnanuntana A, Chang TL, Doty S, Schneider R, Lane JM. Multimodality treatment of a multifocal osteoblastoma-like tumor of the lower extremity. Skeletal Radiology. 2012 Sep;41(9):1153-61. Mancuso CA, Choi TN, Westermann H, Wenderoth S, Hollenberg JP, Wells MT, Isen AM, Jobe JB, Allegrante JP, Charlson ME. Increasing physical activity in patients with asthma through positive affect and self-affirmation: a randomized trial. Archives of Internal Medicine. 2012 Feb 27;172(4):337-43. Mancuso CA, Perna M, Sargent AB, Salmon JE. A pilot study of office-based spirometry in patients with systemic lupus erythematosus. Lupus. 2012. Aug 8 (ePub). Mancuso CA, Peterson MG, Gaeta TJ, Fernández JL, Birkhahn RH. Time to seeking emergency department care for asthma: self-management, clinical features at presentation, and hospitalization. Journal of Asthma. 2012 Apr;49(3):275-81. Mancuso CA, Ranawat AS, Meftah M, Koob TW, Ranawat CS. Properties of the patient administered questionnaires: new scales measuring physical and psychological symptoms of hip and knee disorders. The Journal of Arthroplasty. 2012 Apr;27(4):575-82. Manvelian G, Daniels S, Gibofsky A. The pharmacokinetic parameters of a single dose of a novel nano-formulated lower dose oral diclofenac. Postgraduate Medicine. 2012 Jan;124(1):117-23. 28

Division of Rheumatology

Monach PA, Kümpers P, Lukasz A, Tomasson G, Specks U, Stone JH, Cuthbertson D, Krischer J, Carette S, Ding L, Hoffman GS, Iklé D, Kallenberg CG, Khalidi NA, Langford CA, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Haubitz M, Merkel PA. Circulating angiopoietin-2 as a biomarker in ANCAassociated vasculitis. PLoS One. 2012;7(1):e30197. Monach PA, Tomasson G, Specks U, Stone JH, Cuthbertson D, Krischer J, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Ikle D, Kallenberg CG, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Gu YZ, Snyder RD, Merkel PA. Circulating markers of vascular injury and angiogenesis in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis & Rheumatism. 2011 Dec;63(12):3988-97. Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Iklé D, Kallenberg CG, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCAassociated vasculitis. Annals of the Rheumatic Diseases. 2012 Sep 12. Epub ahead of print. Nair A, Kanda V, Bush-Joseph C, Verma N, Chubinskaya S, Mikecz K, Glant TT, Malfait AM, Crow MK, Spear GT, Finnegan A, Scanzello CR. Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to toll-like receptor 4 and toll-like receptor 2 ligands via soluble CD14. Arthritis & Rheumatism. 2012 Jul;64(7):2268-77. Niewold TB, Kelly JA, Kariuki SN, Franek BS, Kumar AA, Kaufman KM, Thomas K, Walker D, Kamp S, Frost JM, Wong AK, Merrill JT, Alarcón-Riquelme ME, Tikly M, Ramsey-Goldman R, Reveille JD, Petri MA, Edberg JC,

Kimberly RP, Alarcón GS, Kamen DL, Gilkeson GS, Vyse TJ, James JA, Gaffney PM, Moser KL, Crow MK, Harley JB. IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2012 Mar;71(3):463-68. Ostensen M, Brucato A, Carp H, Chambers C, Dolhain RJ, Doria A, Förger F, Gordon C, Hahn S, Khamashta M, L ockshin MD, Matucci-Cerinic M, Meroni P, Nelson JL, Parke A, Petri M, Raio L, Ruiz-Irastorza G, Silva CA, Tincani A, Villiger PM, Wunder D, Cutolo M. Pregnancy and reproduction in autoimmune rheumatic diseases. Rheumatology (Oxford). 2011 Apr;50(4):657-64. Otero M, Favero M, Dragomir C, Hachem KE, Hashimoto K, Plumb DA, Goldring MB. Human chondrocyte cultures as models of cartilage-specific gene regulation. Methods in Molecular Biology. 2012;806:301-36. Otero M, Plumb DA, Tsuchimochi K, Dragomir CL, Hashimoto K, Peng H, Olivotto E, Bevilacqua M, Tan L, Yang Z, Zhan Y, Oettgen P, Li Y, Marcu KB, Goldring MB. E74-like factor 3 (ELF3) impacts on matrix metalloproteinase 13 (MMP13) transcriptional control in articular chondrocytes under proinflammatory stress. The Journal of Biological Chemistry. 2012 Jan 27;287(5):3559-72. Park-Min KH, Lee EY, Moskowitz NK, Lim E, Lee SK, Lorenzo JA, Huang C, Melnick AM, Purdue PE, Goldring SR, Ivashkiv LB. Negative regulation of osteoclast precursor differentiation by CD11b and β2 integrin-BCL6 signaling. Journal of Bone and Mineral Research. 2012 Aug 14. Epub ahead of print. Paul O, Barker JU, Lane JM, Helfet DL, Lorich DG. Functional and radiographic outcomes of intertrochanteric hip fractures treated with calcar reduction, compression, and trochanteric entry nailing. Journal of Orthopaedic Trauma. 2012 Mar;26(3):148-54. Perlman SL, Fabrizio L, Shaha SH, Magid SK. Response to medication dosing alerts for pediatric inpatients using a computerized provider order entry system. Applied Clinical Informatics. 2011;Vol 2; Issue 4:522-33. Peterson MG, Gaeta TJ, Birkhahn RH, Fernández JL, Mancuso CA. History of symptom triggers in patients presenting to the emergency department for asthma. Journal of Asthma. 2012 Aug;49(6):629-36. Pineles D, Valente A, Warren B, Peterson MG, Lehman TJ, Moorthy LN. Worldwide incidence and prevalence of pediatric onset systemic lupus erythematosus. Lupus. 2011 Oct;20(11):1187-92.

Poultsides LA, Ghomrawi HM, Lyman S, Aharonoff GB, Mancuso CA, Sculco TP. Change in preoperative expectations in patients undergoing staged bilateral primary total knee or total hip arthroplasty. The Journal of Arthroplasty. 2012 Oct;27(9):1609-15. Prasarn ML, Ahn J, Helfet DL, Lane JM, Lorich DG. Bisphosphonate-associated femur fractures have high complication rates with operative fixation. Clinical Orthopaedics and Related Research. 2012 Aug;470(8):2295-301. Prince FHM, Bykerk VP, Shadick NA, Lu B, Cui J, Frits M, Iannaccone CK, Weinblatt ME, Solomon DH. Sustained rheumatoid arthritis remission is uncommon in clinical practice. Arthritis Research & Therapy. 2012 Mar 19;14(2):R68. Pyne L, Bykerk VP, Boire G, Haraoui B, Hitchon C, Thorne JC, Keystone EC, Pope JE, CATCH Investigators. Increasing treatment in early rheumatoid arthritis is not determined by the disease activity score but by physician global assessment: results from the CATCH study. Journal of Rheumatology. 2012 Nov;39(11):2081-87. Qing X, Koo GC, Salmon JE. Complement regulates conventional DC-mediated NK-cell activation by inducing TGF-β1 in Gr-1+ myeloid cells. European Journal of Immunology. 2012 42:1723-34. Rebolledo BJ, Unnanuntana A, Lane JM. A comprehensive approach to fragility fractures. Journal of Orthopaedic Trauma. 2011 Sep;25(9):566-73. Rebolledo BJ, Unnanuntana A, Lane JM. Bilateral pathologic hip fractures associated with antiretroviral therapy: a case report. The Journal of Bone & Joint Surgery (Am). 2011 Jul 20;93(14):e78. Ricciardi BF, Paul J, Kim A, Russell LA, Lane JM. Osteoporosis drug therapy strategies in the setting of disease-modifying agents for autoimmune disease. Osteoporosis International. 2012 Sep 7. Epub ahead of print. Saleh A, Vyas PA, Lane JM. Commentary: Hypovitaminosis D in patients undergoing kyphoplasty is associated with increased risk of subsequent vertebral fractures. The Spine Journal. 2012 Apr;12(4):313-14. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012 Aug;51(2):249-57. Schulman E, Chen K, Saboeiro G, Sanders A, Kirou K, Spiera RF, Bass AR, Erkan D. Cyclophosphamide responsive interstitial lung disease in “overlap syndrome”: a clinical pathology conference held by the Division of Rheumatology at the Hospital for Special Surgery. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery. 2011 Feb;7(1):99-105.

Division of Rheumatology

2011-2012 Selected publications

Shapira I, Andrade D, Allen SL, Salmon JE. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis & Rheumatism. 2012 Aug;64(8):2719-23. Shindle MK, Endo Y, Warren RF, Lane JM, Helfet DL, Schwartz EN, Ellis SJ. Stress fractures about the tibia, foot, and ankle. Journal of the American Academy of Orthopaedic Surgeons. 2012 Mar;20(3):167-76. Singer O, Cigler T, Moore AB, Levine AB, Hentel K, Belfi L, Do HT, Mandl LA. Defining the aromatase inhibitor musculoskeletal syndrome: a prospective study. Arthritis Care & Research (Hoboken). 2012 Jun 21. Epub ahead of print. Sinha N, Shieh A, Stein EM, Strain G, Schulman A, Pomp A, Gagner M, Dakin G, Christos P, Bockman RS, Increased PTH and 1.25(OH)(2) D levels associated with increased markers of bone turnover following bariatric surgery. Obesity. 2011 Dec;19(12):2388-93. Smolen JS, van der Heijde DM, Keystone EC, van Vollenhoven RF, Goldring MB, Guérette B, Cifaldi MA, Chen N, Liu S, Landewé RB. Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate. Annals of the Rheumatic Diseases. 2012 Aug 22. Epub ahead of print. Spiera R, Westhovens R. Provisional classification [corrected] criteria for polymyalgia rheumatica: moving beyond clinical intuition? Arthritis & Rheumatism. 2012 Apr;64(4):955-57. Erratum in: Arthritis & Rheumatism. 2012 Jul;64(7):2416. Sreih A, Ezzeddine R, Leng L, LaChance A, Yu G, Mizue Y, Subrahmanyan L, Pons-Estel BA, Abelson KA, Gunnarsson I, Svenungsson E, Cavett, J, Glenn S, Zhang L, Montgomery P, Perl A, Salmon, J, Alarcón-Riquelme MS, Harley JB. Dual effect of the macrophage migration inhibitory factor gene on the development and severity of human systemic lupus erythematosus. Arthritis & Rheumatism. 2011 Dec; 63: 3942-51.

Tomasson G, Boers M, Walsh M, LaValley M, Cuthbertson D, Carette S, Davis JC, Hoffman GS, Khalidi NA, Langford CA, McAlear CA, McCune WJ, Monach PA, Seo P, Specks U, Spiera R, St Clair EW, Stone JH, Ytterberg SR, Merkel PA. Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener’s). Arthritis Care and Research (Hoboken). 2012 Feb;64(2): 273-79. Tonge C, Erkan D. Antiphospholipid syndrome. RAED Journal. 2011;3(1-2):11-19. Uludag O, Erkan D, Lockshin MD. Clinical image: cognitive or cosmetic dysfunction? Arthritis & Rheumatism. 2012. Published online. Unnanuntana A, Ashfaq K, Ton QV, Kleimeyer JP, Lane JM. The effect of long-term alendronate treatment on cortical thickness of the proximal femur. Clinical Orthopaedics and Related Research. 2012 Jan;470(1):291-98. Unnanuntana A, Mait JE, Shaffer AD, Lane JM, Mancuso CA. Performance-based tests and self-reported questionnaires provide distinct information for the preoperative evaluation of total hip arthroplasty patients. The Journal of Arthroplasty. 2012 May;27(5):770-75. Unnanuntana A, Rebolledo BJ, Gladnick BP, Nguyen JT, Sculco TP, Cornell CN, Lane JM. Does vitamin D status affect the attainment of in-hospital functional milestones after total hip arthroplasty? The Journal of Arthroplasty. 2012 Mar;27(3):482-89. Unnanuntana A, Rebolledo BJ, Khair MM, DiCarlo EF, Lane JM. Diseases affecting bone quality: beyond osteoporosis. Clinical Orthopaedics and Related Research. 2011 Aug;469(8): 2194-206. Unnanuntana A, Saleh A, Nguyen JT, Sculco TP, Cornell CN, Mancuso CA, Lane JM. Low vitamin D status does not adversely affect short-term functional outcome after total hip arthroplasty. The Journal of Arthroplasty. 2012 Jul 12. Epub ahead of print.

Stirzaker R A, Biswas PS, Gupta S, Song L, Bhagat G, Pernis AB. Administration of Fasudil, a ROCK inhibitor, attenuates disease in lupus-prone NZB/W F1 female mice. Lupus. 2012 May;21(6):656-61.

Unnanuntana A, Ton QV, Kleimeyer JP, Nguyen JT, Lane JM. A fracture does not adversely affect bone mineral density responses after teriparatide treatment. Clinical Orthopaedics and Related Research. 2012 Mar;470(3): 927-36.

Tavares R, Pope JE, Tremblay J-L, Thorne JC, Bykerk VP, Lazovskis J, Blocka KLN, Bell MJ, et al. Early management of newly diagnosed rheumatoid arthritis by Canadian rheumatologists: a national, multicenter, retrospective cohort. The Journal of Rheumatology. 2011 Nov;38(11):2342-45.

Vasudevan A, DiCarlo EF, Wright T, Chen D, Figgie MP, Goldring SR, Mandl LA. Cellular response to prosthetic wear debris differs in patients with and without rheumatoid arthritis. Arthritis & Rheumatism. 2012 Apr;64(4):1005-14.

Division of Rheumatology

Villeneuve E, Nam J, Bell MJ, Deighton CM, Felson DT, Hazes JM, McInnes IB, Silman AJ, Solomon DH, Thompson AE, White PH, Bykerk VP, Emery P. A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis. Annals of the Rheumatic Diseases Online First, published on April 24, 2012. Walters HM, Pan N, Moorthy LN, Ward MJ, Peterson MG, Lehman TJ. Patterns and influence of familial autoimmunity in pediatric systemic lupus erythematosus. Pediatric Rheumatology Online Journal. 2012 Aug 14;10(1):22. Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM, Crish JF, Bebek G, Ritter SY, Lindstrom TM, Hwang I, Wong HH, Punzi L, Encarnacion A, Shamloo M, Goodman SB, Wyss-Coray T, Goldring SR, Banda NK, Thurman JM, Gobezie R, Crow MK, Holers VM, Lee DM, Robinson WH. Identification of a central role for complement in osteoarthritis. Nature Medicine. 2011 Nov 6;17(12): 1674-79. Whittle SL, Colebatch AN, Buchbinder R, Edwards CJ, Adams K, Englbrecht M, Hazlewood G, Marks JL, Radner H, Ramiro S, Richards BL, Tarner IH, Aletaha D, Bombardier C, Landewe RB, Mu¨ller-Ladner U, Bijlsma JWJ, Branco JC, Bykerk VP, da Rocha G, Pinheiro C, Catrina AI, Hannonen P, Kiely P, Leeb B, Lie E, Martinez-Osuna P, Montecucco C, Østergaard M, Westhovens R, Zochling J, van der Heijde D. Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative. The Journal of Rheumatology (Oxford). 2012 Aug;51(8):1416-25. Xu H, Zhu J, Smith S, Foldi J, Zhao B, Chung AY, Outtz H, Kitajewski J, Shi C, Weber S, Saftig P, Li Y, Ozato K, Blobel CP, Ivashkiv LB, Hu X. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nature Immunology. 2012 May 20; 13(7):642-50. Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by Janus kinase inhibitors. Arthritis & Rheumatism. 2012 Aug 31. Epub ahead of print. Yuan F, Quan LD, Cui L, Goldring SR, Wang D. Development of macromolecular prodrug for rheumatoid arthritis. Advanced Drug Delivery Reviews. 2012 Sep;64(12):1205-19. Zhao B, Grimes SN, Li S, Hu X, Ivashkiv LB. TNF-induced osteoclastogenesis and inflammatory bone resorption are

inhibited by transcription factor RBP-J. The Journal of Experimental Medicine. 2012 Feb 13;209(2):319-34. Zifchock RA, Kirane Y, Hillstrom H; Hospital for Special Surgery Lower Extremity Realignment Research Group. Are joint structure and function related to medial knee OA pain? A pilot study. Clinical Orthopaedics and Related Research. 2011 Oct;469(10):2866-73. TEXTBOOKS Erkan D, Pierangeli S (Eds). Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies. Springer, 2012. TEXTBOOK CHAPTERS Biswas PS, Kang K, Gupta S, Bhagat G, Pernis AB. A Murine Autoimmune Model of Rheumatoid Arthritis and Systemic Lupus Erythematosus Associated with Deregulated Production of IL-17 and IL-21. In Autoimmunity: Methods and Protocols. Perl A (Ed). Humana Press, 2012;900:233-51. Espinosa G, Berman H, Erkan D, Cervera R. Task Force Report on Catastrophic Antiphospholipid Syndrome. In Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies, 1st edition. Erkan D, Pierangeli S (Eds). Springer, 2012;181-93. Erkan D, Pierangeli S, Lockshin MD. Task Force Report on Antiphospholipid Syndrome Clinical Research. In Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies, 1st edition. Erkan D, Pierangeli S (Eds). Springer, 2012;247-57. Erkan D, Rahman A, Cohen H, Machin SJ, Pierangeli S. What Are the Potential Future Treatments in Antiphospholipid Syndrome? In Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies, 1st edition. Erkan D, Pierangeli S (Eds). Springer, 2012;261-87. Erkan D, Lally L, Lockshin MD. What Should Patients Know About Antiphospholipid Antibodies and Antiphospholipid Syndrome. In Antiphospholipid Syndrome: Insights and Highlights from the 13th International Congress on Antiphospholipid Antibodies, 1st edition. Erkan D, Pierangeli S (Eds). Springer, 2012;295-309. Sanders KH, Erkan D. Perioperative Management of Antiphospholipid Antibody Positive Patients During Non-cardiac Surgeries. In Perioperative Management of Patients with Rheumatic Disease, 1st edition. Mandell BF (Ed). Springer 2012;91-107.

Division of Rheumatology

DIVISION OF RHEUMATOLOGY/DEPARTMENT OF MEDICINE

Physician-in-Chief and Director of Medicine Mary K. Crow, MD 212.606.1397 Perioperative Medicine Division Linda A. Russell, MD 212.606.1305 Rheumatology Faculty Practices Theodore R. Fields, MD, FACP 212.606.1286 Rheumatology Fellowship Program Anne R. Bass, MD, FACP 212.774.2189 Pediatric Rheumatology Fellowship Program Alexa B. Adams, MD 212.774.2083 HSS Academy of Rheumatology Medical Educators Stephen A. Paget, MD, FACP, MACR 212.606.1845 Divisional Administrator for Rheumatology Laughlin E. Rice, MBA 646.797.8487

Division of Rheumatology

Centers of Excellence Directors Inflammatory Arthritis Center Sergio Schwartzman, MD 212.606.1957 Vivian P. Bykerk, MD 212.774.7520 Systemic Lupus Erythematosus and Antiphospholipid Syndrome Jane E. Salmon, MD 212.606.1422 Scleroderma, Vasculitis, and Myositis Robert F. Spiera, MD 212.774.2048 Metabolic Bone Disease and Osteoporosis Linda A. Russell, MD 212.606.1305 Pediatric Rheumatology Thomas J.A. Lehman, MD, FAAP 212.606.1151

pathways to The Division of Rheumatology at Hospital for Special Surgery fosters a scientific environment that supports interdisciplinary, collaborative, and productive research in each of its centers of excellence and expedites the translation of discoveries in the laboratories to generate new and innovative therapies for patients. Informing the work of the Divisionâ&#x20AC;&#x2122;s clinicians and scientists is a wealth of patient data that is available and growing in Hospital-based registries established in each of the autoimmune and rheumatic disease

Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The Inflammatory Arthritis Center pursues a continuum of research, from studying the role of tumor necrosis factor (above) and mechanisms of the Notch intracellular molecular pathway, to developing patient registries for rheumatoid arthritis, ankylosing spondylitis, and other inflammatory diseases that promote advances in clinical care. Unique collaborations among rheumatologists and orthopaedic surgeons are helping to identify ways of improving perioperative outcomes in patients with rheumatic disease who undergo surgery at HSS.

categories. The Divisionâ&#x20AC;&#x2122;s 2011-2012 Annual Report highlights some of the key basic, translational, and clinical studies underway that promise to influence the field of rheumatology and improve outcomes for patients the world over. Osteoarthritis In the last few years, osteoarthritis (OA) has come under increasing scrutiny as both basic and clinical researchers grapple with the impact that this painful and disabling disease is expected to have on the public health of the nation as the population ages. At HSS, OA research is taking place on many levels, including studies of nonoperative management of OA, the creation of a nonsurgical knee OA patient registry, and the development of synthetic implants to reduce high forces on the tibia (above) after meniscal repair.

o discovery Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Metabolic Bone Disease and Osteoporosis

Clinicians and scientists that comprise the Systemic Lupus Erythematosus and Antiphospholipid Syndrome Center have a longstanding history of accomplishments in the study of lupus and its potential for multiple organ involvement. The important PROMISSE study continues to uncover information guiding therapeutic decisions, and its researchers are now pursuing investigations of genes that may be associated with renal function (above). Other research focuses on compounds that can reverse T-cell dysfunction that leads to lupus.

Bone health has always been a subject of significant research at Hospital for Special Surgery. Some 25 years ago, HSS was one of the first institutions in the country to establish a comprehensive center focused on the prevention and treatment of osteoporosis, and it continues to be at the forefront of research in osteoporosis and other metabolic bone diseases. Research in bone quality is taking place in the laboratories, while clinicians address bone health in their practices.

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Scleroderma, Vasculitis, and Myositis HSS researchers have made extraordinary progress conducting clinical trials for new therapies for scleroderma, vasculitis, and myositis, including the largest study of scleroderma patients treated with imatinib and the groundbreaking NIH-sponsored RAVE trial leading to rituximab becoming the first FDA-approved drug for ANCAassociated vasculitis. Currently there are some 15 clinical trials and observational studies in progress looking at vascular issues (above) and other complications of systemic sclerosis.

Pediatric Rheumatology HSS pediatric rheumatologists are dedicated to taking care of children whose diseases are difficult to diagnose or treat. The pediatric rheumatologists have pioneered new therapies for lupus and juvenile arthritis â&#x20AC;&#x201C; often characterized by swollen lymph nodes (above) â&#x20AC;&#x201C; that are now widely accepted practices across the country. These include the combined rituximab and cytoxan therapy for children with severe SLE and lupus nephritis that has dramatically improved outcomes for these patients.

DIVISION OF RHEUMATOLOGY The 2011-2012 Annual Report of the Division of Rheumatology is produced by Education & Academic Affairs of Hospital for Special Surgery. Laura Robbins, DSW Senior Vice President Education and Academic Affairs Designated Institutional Officer, GME Marcia Ennis Director Education Publications and Communications

ABOUT HOSPITAL FOR SPECIAL SURGERY

Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopaedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopaedics, No. 3 in rheumatology, No. 10 in neurology, and No. 5 in geriatrics by U.S.News & World Report (2012-13), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center three consecutive times. HSS has one of the lowest infection rates in the country. From 2007 to 2011, HSS has been a recipient of the HealthGrades Joint Replacement Excellence Award. HSS is a member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The hospitalâ&#x20AC;&#x2122;s research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at www.hss.edu.

Hospital for Special Surgery 535 East 70th Street New York, NY 10021 212.606.1000 www.hss.edu