HSS Division of Rheumatology | Annual Report 2016

Our singular impact emerges from our people, our history, our collegiality, and our focused commitment to improving lives.

Division of Rheumatology

Annual Report 2016

A unique chemistry has propelled Hospital for Special Surgery (HSS) to become the world’s leading academic medical center dedicated to musculoskeletal health with the largest group of rheumatologists in the nation.

Highly skilled clinical care, cutting-edge biomedical research and education coalesce to explore and uncover the etiologies and pathologies behind rheumatic diseases.

A culture of collaboration and communication elevates basic biological discoveries to inform translational and clinical research that improves patient lives, within the institution’s walls and worldwide.

Table of Contents

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Message from Physician-in-Chief and Chief, Division of Rheumatology, Dr. Mary K. Crow

Pillars of HSS Rheumatology

Clinical Care

Research

Education

Professional Staff

Selected Notable Publications

HSS Contact Information

Message from Physician-in-Chief and Chief, Division of Rheumatology

Mary K. Crow, MD Physician-in-Chief & Chair, Department of Medicine, Chief of the Division of Rheumatology and the Benjamin M. Rosen Chair in Immunology and Inflammation Research Hospital for Special Surgery

Annual Report 2016

Research programs, academic departments, and health care institutions that function at a high level are often described as representing “more than the sum of their parts.” I believe the HSS Division of Rheumatology’s impact goes beyond this distinction, giving rise to wholly new and unique benefits to the field. All that HSS Rheumatology encompasses — ​its special, patient centered approach to research and clinical care — ​emerges from our people, our history, our collegiality, our talents, and our focused commitment to improving lives. It is a phenomenon that derives from attention to the patient with every effort and activity — ​whether clinical care, research, education, or service — ​and generates something entirely novel and powerful: a force for improving patient outcomes, advancing medical care worldwide, and generating a network of collaborative and committed physicians, scientists, and staff with the power to make the world a better place and to achieve the highest level of professional reward for themselves.

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Of course, the rewards that come from membership in a highly focused and ambitious department — ​ a department that integrates excellent clinical care with a multifaceted academic program — ​can be achieved only through dedication. The year 2016 was a year that showcased the commitment, effort, and impact of all members of our department and staff.

One indication of our department’s excellence is the recognition of one of our own through one of the highest honors in academic medicine. I am pleased to announce that Dr. Jane Salmon, Collette Kean Research Professor at HSS and associate dean of faculty affairs at Weill Cornell Medicine, was elected this year to the National Academy of Medicine. This honor reflects Dr. Salmon’s pioneering research which has advanced the understanding of autoimmunity, lupus, and pregnancy, conditions that particularly affect women.

We realize that the clear dividends that we have gained in improving our patients’ lives and fostering medical advances — ​and the gratification that comes from engagement in HSS Rheumatology — ​will only be amplified through our ongoing transformation.

We aim to evolve our clinical structure into one that incorporates all of our physicians and staff into teams while continuing to nurture the personal relationship between physician and patient. This year, we redesigned our administrative and nursing staff functions with the goal of establishing collaborative pods comprising physicians, administrative staff and nursing staff that are knowledgeable about the clinical problems affecting the patients. This ambitious revision of our clinical operations continues to undergo refinements, but the benefits to our patients from the collaborative support of our administrative and ­nursing staff are already making our outstanding clinical care even better.

We always look to the future and to how we can continue to increase our effectiveness and our contributions to the community and to medicine. In 2016, we welcomed three new rheumatologists to our faculty, each with special talents that will amplify what we can achieve as a leading department of rheumatology. David Fernandez, MD, PhD, is what used to be called a “triple threat.” That distinction is difficult to achieve in the current environment, where patient

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care is accompanied by many new tasks and responsibilities and where research funding opportunities, at least through government sources, are increasingly limited. David received his MD and PhD from SUNY Upstate Medical University in Syracuse, where he worked under Andras Perl to define the signaling pathways implicated in altered T-cell function in lupus patients. David was first author on two highly cited papers that described the effect of rapamycin and the role of the mammalian target of rapamycin in lupus T-cell activation. At HSS David will continue to develop a career focused on translational studies aimed at defining mechanisms of systemic autoimmune disease and will maintain his outstanding clinical skills with a limited time commitment to the management of patients with lupus and inflammatory muscle disease.

Shanthini Kasturi, MD, MS, has joined the HSS Rheumatology faculty to further develop the outstanding work she initiated during her fellowship and master’s program — ​training focused on the utility of patient-reported outcomes in clinical research studies and patient management. Shanthini used the Patient Reported Outcomes Measurement Information System (PROMIS) to document that lupus patients can successfully generate meaningful data that can potentially be employed to guide their care. She will be continuing her research studies with the support of a grant from the Rheumatology Research Foundation.

Lastly, Sarah Taber, MD, has joined our faculty in pediatric rheumatology to develop a clinical practice with a particular interest in the systemic autoimmune diseases. During her fellowship at HSS, Sarah led a study of the potential for genetic mosaicism to contribute to the pathology of linear scleroderma.

I anticipate that all three new rheumatologists, along with Dr. Lindsay Lally, who was recruited to the faculty last year and is featured in this report, will be valued and valuable members of our department for many decades to come.

One of the most significant features of HSS Rheu­ matology is the close and productive engagement between our clinicians and our researchers — ​with physician scientists leading laboratory and translational studies that unravel disease mechanisms,

Message from Physician-in-Chief

elucidate links between underlying biology and clinical manifestations of disease, and identify new therapeutic targets. In this year’s report we feature Carl Blobel, MD, PhD, Director of our Arthritis and Tissue Degeneration Research Program. Carl is well known for his discovery — ​together with his wife, Gisela Weskamp, PhD — ​of the ADAM ­family metalloprotease-­ d isintegrins. In recent years, Carl has led studies of a protein that regulates the function of those enzymes. These findings have significant potential implications for designing new therapies for inflammatory diseases. Carl exemplifies the value of productive collaboration with other members of our faculty, as his recent publications describe research conducted together with Jane Salmon, L ­ ionel I­ vashkiv and Mary Goldring.

The team approach is also a feature of my own research program, focused primarily on dissecting the underlying mechanisms responsible for systemic lupus erythematosus (SLE). One view of the type of research I do treats it as a precursor to “precision medicine,” or “personalized medicine,” as it is aimed at understanding the relevant mechanisms, therapeutic targets, and ultimately the optimal therapies specific to the individual patient. I prefer to think of my research as an effort to gain insight into why and how patients get disease. Individual differences are part of the equation, and our detailed clinical characterization of individual patients with lupus or related autoimmune diseases underlies our investigation of the relative contribution of the type I interferon pathway and other molecular pathways to the autoimmunity and tissue damage that result in clinical disease.

This work would not move forward without the coordinated efforts of a team — ​including those of Kyriakos Kirou, MD, DSc, a skilled rheumatologist with laboratory experience who identifies appropriate patients for study and is the HSS lead investigator on lupus clinical trials. Our team also includes Mikhail Olferiev, MD, a brilliant investigator who has developed c ­ reative approaches to the analysis of clinical and gene expression data; our study coordinator, who collects and records clinical data from our patients; our laboratory technician, who processes s ­ amples and prepares them for analysis; and of course,

Annual Report 2016

our patients. In view of the impressive results of a recent phase II clinical trial of a monoclonal antibody specific to the interferon receptor, it has been particularly gratifying for our entire team to see the fruits of our investigation into the role of type I interferon in SLE over the past 15 years, moving toward a potential new treatment for patients.

Rheumatologists, by virtue of the comprehensive nature of the medical conditions we treat, and our ­puzzle-­solving cognitive style, are among the most dedicated and important educators of future physicians. HSS Rheumatology values and prioritizes teaching and research that advance education beyond what comes naturally to many of us. The HSS Academy of Rheumatology Medical Educators is a unique program, developed by Dr. Stephen Paget and co-led by Dr. Jessica Berman. The Academy has not only shone a light on the importance of teaching skills but has funded education research projects that have developed new techniques for measuring student achievement, including a study measuring learning by rheumatology fellows in a clinical research journal club, led by Drs. Juliet Aizer and Lisa Mandl. Dr. Aizer and Dr. Ed Parrish also have ­important leadership roles in the curriculum development and teaching oversight of first- and second-year medical students at Weill Cornell Medical College.

All of these efforts, people, achievements and more come together — ​or “emerge” — ​as the very special entity that is HSS Rheumatology. I hope you enjoy reading our report, and I invite you to reach out to us to discuss your complex patients, your ideas for study of a novel disease mechanism, or your new approaches to communicating with our students effectively. Together, we will continue to evolve our department in order to advance the field.

Mary (Peggy) K. Crow, MD Physician-in-Chief and Chair, Department of Medicine, Chief of the Division of Rheumatology and the Benjamin M. Rosen Chair in Immunology and Inflammation Research

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Pillars of HSS Rheumatology 1.

Clinical Care

2.

Research

3.

Education

Bettering Patient Outcomes The ultimate goal of HSS’s commitment to cutting-edge research and providing the best in rheumatology education is to improve patient outcomes and lives. Our rheumatologists go beyond providing outstanding patient management to making HSS the best a hospital can be. Members of our faculty provide leadership in administrative and clinical management roles, engaging with multidisciplinary teams to ensure that our patients achieve optimal outcomes in an environment that is both personal and that meets our high standards in every way. Whether we are identifying predictors of successful joint surgery, identifying the biomarkers of successful pregnancy outcome in lupus patients, or promoting improved medication compliance through our patient support programs, our focus is on doing the best we can for our patients.

Innovations and Advances As our strong record of peer-reviewed publications and presentations at rheumatology and specialty scientific conferences attest, HSS is home to a rich, collaborative culture of scientific and clinical research. HSS faculty are defining the complex molecular pathways and pathologies underlying rheumatologic conditions, laying the groundwork that will ultimately translate cutting-edge science into better clinical care. The collaborative studies of our patients — ​in the clinic and the lab — ​led by clinicians, physician scientists and basic researchers, are identifying novel treatment targets — ​many of which are or will soon be under investigation in therapeutic trials — ​ and guiding us toward new standards of rheumatology practice.

Training for the Future Our dedication to our fellows is second only to our dedication to our patients. At the core of the HSS mission to go beyond excellence is not only our commitment to train the next generation of outstanding rheumatologists but to foster and mentor future leaders in academic medicine. In addition to our formal curriculum for medical students, residents and fellows, and our weekly lectures by leaders in the field, HSS Rheumatology is creating novel methods and tools to advance professional education. HSS rheumatologists developed the HSS Academy of Rheumatology Medical Educators, supporting innovative education research studies. Our faculty also contribute to progress in the field through their leadership roles in the American College of Rheumatology (ACR), the Rheumatology Research Foundation, and disease-focused research-funding organizations.

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Pillars of HSS Rheumatology

Annual Report 2016

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Clinical Care Introduction

While rheumatologists describe clinical entities and conditions as distinct diseases, in fact we know that each patient m ­ anifests their disease in their own unique way, so we strive to evaluate and treat each patient as an individual.

The optimal management of rheumatologic disease requires integrating a patient’s unique biology and patho­ physiology with both patient-­derived reports and findings from clinical and laboratory assessments. The collective insights into each patient’s clinical profile — ​which are informed by our research into rheumatologic disease mechanisms — ​allow us to better individualize treatment, enrich patient m ­ anagement, and ultimately improve patient outcomes and well-being.

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Clinical Care

An integrated approach to patient care improves outcomes and well–being

Ongoing research by Dr. Lindsay Lally, for example, is helping physicians better understand and treat vasculitis, a group of rare disorders with myriad clinical manifestations and often complex patient presentations.

Translational studies by Dr. Lally and colleagues, published in 2015 in Rheumatology, confirmed the diagnostic utility of assessing rho kinase (ROCK) activity to enhance the sensitivity of temporal artery biopsies in diagnosing giant cell arteritis (GCA).

Aberrant ROCK activity is implicated in several vascular disorders; by staining temporal artery biopsies for phosphorylated ezrin/radixin/moesin (pERM), a surrogate marker of ROCK activity, the authors determined that GCA patients had more intense pERM staining compared with age- and sex-­matched controls, regardless of whether biopsies were positive or negative by routine histopathology.

Annual Report 2016

“There may be immediate diagnostic implications here,” says Dr. Lally, adding that this staining may increase the sensitivity of biopsy, which, while considered the gold standard diagnostic test, is often negative in patients who actually have GCA. These results were recently confirmed by Dr. Lally and colleagues in a larger cohort of patients. “In the future, we would like to further investigate if altering this pathway may have a therapeutic role in GCA,” she says.

Other research being led by Dr. Lally under the mentorship of Dr. Robert Spiera is a pilot study assessing the efficacy of treating polymyalgia rheumatic (PMR) by blocking the pro-­inflammatory cytokine ­interleukin-6 (IL-6). Recently published in Arthritis &

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Working to improve the gold standard for diagnostic testing Lindsay Lally, MD

Arthur Yee, MD, PhD

Assistant Attending Rheumatologist, Hospital for Special Surgery Assistant Professor of Medicine, Weill Cornell Medical College

Assistant Attending Physician, Hospital for Special Surgery Assistant Professor of Medicine, Weill Cornell Medical College

Rheumatology — ​and the first prospective study targeting this important molecule in newly diagnosed PMR — ​Dr. Lally reported that IL-6 blockade with the biologic drug tocilizumab resulted in all subjects reaching the trial’s primary end-point of ­relapse-free remission off glucocorticoids at 6 months. “The most exciting finding of this study was that the use of tocilizumab dramatically decreased the dose and duration of corticosteroid treatment in PMR. Most of the morbidity from PMR is related to corticosteroid toxicity, and with this strategy, we may be able to prevent many dreaded complications in our patients.”

Moreover, Dr. Lally’s group is engaged in translational studies exploring specific ­treatment- and ­disease-​ ­related gene signatures in PMR, findings that could further help clinicians customize care to the individual patient.

Similar to Dr. Lally’s focus on improving the understanding, diagnosis and management of vasculitis, Dr. Arthur Yee has a particular interest in another rare rheumatologic disease: sarcoidosis.

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The care of patients with sarcoidosis has historically fallen under the auspices of other subspecialists.

However, given its systemic nature and its potential to involve any organ, Dr. Yee has advocated for a prominent role for rheumatologists. As he recently wrote in a 2016 article in Best Practice & Research in Clinical Rheumatology, “with increased appreciation of the systemic nature of this disorder and the availability of more therapeutic options, it is clear that a multidisciplinary approach, with the rheumatologist as a key component, can offer more optimal care.”

After joining the faculty at HSS, Dr. Yee pioneered the use of anti-tumor necrosis factor (TNF) monoclonal antibodies for the treatment of sarcoidosis. These medications, originally developed for rheumatologic disorders such as rheumatoid arthritis (RA), have since become widely accepted therapeutic options.

Ironically, Dr. Yee’s current interests now include trying to identify select patients who might be able to safely discontinue all medications after treatment with TNF antagonists, promoting the intriguing possibility that sustained true remissions of sarcoidosis can be achieved in some cases through the use of these agents.

Clinical Care

Highlights

Clinical Trials of the Scleroderma, Vasculitis and Myositis Center In collaboration with a number of his colleagues, Dr. Robert F. Spiera is involved in multiple i­nvestigator-­initiated interventional treatment trials for which HSS serves as the study center.

For example, Dr. Lally’s study, referenced earlier and published in 2016 in Arthritis & Rheumatology, found that the RA drug tocilizumab is safe and effective in treating patients with newly diagnosed polymyalgia rheumatica (PMR). PMR patients often experience more symptoms as a result of ste-

Within the context of a general rheumatology practice and while engaging in many academic and administrative activities at HSS and Weill Cornell Medicine, Dr. Yee has cared for close to two hundred patients with documented or suspected sarcoidosis.

He integrates patient management with an academic curiosity set on advancing the understanding and care of the disorder, while at the same time imparting his experiences onto physicians in training.

Dr. Yee is currently conducting an ongoing study cataloguing the nature of consultations requested of HSS rheumatology fellows for questions around the diagnosis and management of known or suspected sarcoidosis. His goal is to identify what assistance and insights other subspecialists are seeking from rheumatologists to help in the care of patients with sarcoidosis and eventually to use his findings to develop a curriculum for rheumatology trainees at HSS and elsewhere.

Annual Report 2016

roid therapy than manifest from the disease itself; the new findings support tocilizumab as a potentially s ­ teroid-­sparing treatment option. Moreover, other research that Dr. Spiera is a part of suggests that tocilizumab might also be effective in temporal arteritis, which commonly co-­occurs with PMR. Along with his colleague Dr. Jessica Gordon, Dr. Spiera also recently co-­authored a study testing the anti-B-cell drug belimumab in patients with scleroderma. Already approved in SLE, belimumab plus background therapy with mycophenolate mofetil (MMF) was not statistically more effective than MMF plus placebo. However, the belimumab group did trend toward better clinical outcomes, while a related trial that looked at gene expression changes in skin biopsies of scleroderma patients found that treated patients demonstrated downregulation in genes involved in B-cell mediated immunity. The findings suggest that belimumab is most likely acting on the correct pathologic pathway and that further testing of the compound in scleroderma is warranted.

“There are plenty of hospitals that treat rheumatoid arthritis really well, and that treat osteoarthritis really well,” says Dr. Spiera, “However other healthcare institutions look to us to manage rarer, harder to treat conditions — ​conditions like scleroderma.”

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2.

Research Introduction

HSS patients are integral to scientific advancement, triggering our imaginations and inspiring questions that form the basis of our research. In many cases our patients are our research subjects. But they are more than that; they are collaborators in helping generate novel insights into some of the most complex disorders in medicine. As research gains are translated into therapeutic advances, patients are increasingly incorporated into our work.

Through careful observation and study of how certain patients respond to a particular therapy and others do not, our next set of research questions is formed. Our patients are true partners in our generation of new knowledge.

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Research

The development of new, effective treatment strategies in rheumatology requires insights derived from patients, as well as those that occur at the bench.

HSS’s large collective of researchers continues to dissect the intricate, immune ­system-­m ediated pathologies behind rheumatologic disorders, discoveries with clear translational potential.

Basic science research led by Dr. Carl Blobel has produced an extremely promising lead in advancing the treatment of conditions such as RA and SLE. For years the pro-­inflammatory cytokine TNFα has been a treatment target in a number of rheumatologic conditions, and TNF-­blocking medications have proven very effective therapies. Recent studies suggest that activation of a second signaling pathway, the EGF-­receptor (EGFR) pathway, also contributes to the pathogenesis of RA and SLE. Both the TNFα

and the epidermal growth factor receptor EGFR ­pathways are controlled by a signaling scissor, the cell surface protease ADAM17 (also referred to as the TNFα-­ c onvertase). Unfortunately, blocking ADAM17 would lead to severe side effects, because the EGFR is required to protect the skin and intestinal integrity. Dr. Blobel’s team has identified novel regulator m ­ olecules of ADAM17, called iRhom 1 and iRhom 2, that regulate the ­ADAM17-­dependent release of TNFα and of ligands of the EGFR from the cellular surface.

The major breakthrough with this work was determining that iRhom 2 specifically controls the activity of ADAM17 in immune cells, which release TNFα and the EGFR-­ligand h ­ eparin-­binding EGF (HB-EGF), while iRhom1 regulates ADAM17 activity everywhere else in the body, including in the skin and

A division working together to study patients over time, developing insights into the drivers of disease

Annual Report 2016

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Mary K. Crow, MD

Mikhail Olferiev, MD

Kyriakos Kirou, MD, DSc

David Fernandez, MD, PhD

Physician-in-Chief & Chair, Department of Medicine, Chief of the Division of Rheumatology and the Benjamin M. Rosen Chair in Immunology and Inflammation Research, Hospital for Special Surgery, Professor of Medicine, Weill Cornell Medical College

Research Associate, Research Division, Hospital for Special Surgery

Assistant Attending Physician, Assistant Scientist, Director, Lupus Nephritis Program, Clinical Co-Director, Mary Kirkland Center for Lupus Care, Hospital for Special Surgery, Assistant Professor of Clinical Medicine, Weill Cornell Medical College

Assistant Attending Physician, Hospital for Special Surgery

gastrointestinal tract. By specifically targeting iRhom 2 in animal models, Dr. Blobel’s team has selectivity suppressed TNFα and HB-EGF release in immune cells, thus avoiding side effects elsewhere in the body.

Importantly, in collaboration with Dr. Jane Salmon, Dr. Blobel has shown that mice lacking iRhom2 are protected from disease in animal models of RA and SLE-­glomerulonephritis.

“To me this is the most exciting translational opportunity we have discovered in the over 30 years I’ve been in science,” says Dr. Blobel, “To be able to separate the pro-­inflammatory functions of ADAM17 in immune cells from the protective function in the skin and intestine is something that 5 years ago we wouldn’t have even dreamt of, and we see a real opportunity to translate this into the clinic.”

Blobel and his collaborators are working to develop antibodies and small molecule drugs that would specifically target iRhom 2 to block TNF release, an approach he feels could be used to treat RA, SLE, and perhaps other rheumatologic disorders as well.

Other research at HSS, in part headed by HSS Department of Medicine Chair, Dr. Mary K. Crow, is helping to uncover other biological mechanisms underlying SLE.

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For over 10 years Dr. Crow has worked in collaboration with Dr. Kyriakos Kirou to develop a longitudinal cohort of lupus patients in order to study the biological and clinical evolution of the disorder over time.

For example, by analyzing serial blood samples from over 200 patients Dr. Crow, Dr. Kirou and colleagues helped discover unique gene expression profiles in those suffering from lupus — ​in other words unique collections of mRNA expressed in their blood cells.

Further, the group determined that the family of immune system molecules that mediate anti-viral host defense, the type I interferons, actually induces these altered gene transcripts and represents an important therapeutic target.

HSS researchers have since continued collecting and analyzing the blood samples from this cohort of patients with increasingly sophisticated techniques.

Research associate Dr. Mikhail Olferiev has been instrumental in advancing this work, developing a specialized database to help analyze the reams of clinical and gene expression data collected over the years. Through these analyses he and his colleagues have helped identify gene transcripts in the blood associated with disease flares, and even those that might help predict an impending flare.

Research

Highlights

Carl Blobel, MD, PhD Senior Scientist, Program Director for the Arthritis and Tissue Degeneration Program, Virginia F. and William R. Salomon Chair in Musculoskeletal Research, Hospital for Special Surgery Professor of Medicine, Professor of Physiology & Biophysics, Weill Cornell Medical College

Similarly, other ongoing work in Dr. Crow’s lab is attempting to understand if there are differences in gene expression in patients who go on to have lupus nephritis compared with those who don’t. If it turns out there are, perhaps treating clinicians would be able to predict who is likely to develop nephritis so they can intervene.

Barbara Volcker Center for Women and Rheumatic Disease Since its inception 20 years ago, The Barbara Volcker Center (BVC) for Women and Rheumatic Disease at HSS has been a leader in advancing the knowledge of g ­ ender-­specific issues in rheumatologic and autoimmune disease. Grants funded by the center support a wide range of research: better understanding sex discrepancies of autoimmune and rheumatic disorders; exploring and treating pregnancy complications in rheumatic disorders due to antiphospholipid syndrome; and better managing patients with overlapping or undifferentiated connective tissue disorders to name a few.

The BVC has also successfully implemented various webbased self-­m anagement tools for patients suffering from rheumatic illness, while also introducing a medical school course on chronic illness into the Weill Cornell Medical College curriculum, a testament to the center’s mission to impart the

As Dr. Crow explains, “Once we validate these transcripts we might have biomarkers indicating that a patient is about to experience a flare, or eventually develop nephritis, and intervene therapeutically.”

principles of chronic illness management to physicians in training at all levels.

Dr. Michael Lockshin, who along with Dr. Crow reviews and awards BVC grants, comments, “BVC addresses broad questions, such as ‘Why women?’, ‘What is the meaning and

Finally, Dr. David Fernandez, a recent graduate of the HSS rheumatology fellowship and newly appointed faculty member, is working to map the cohort data with other biological factors in order to further the understanding and treatment of SLE. Specifically, he is exploring whether or not mitochondrial DNA in the blood could have functional effects on cells and contribute to various manifestations of lupus.

“We all work together to study our patients over time, looking at detailed clinical and laboratory data and trying to link these findings with the underlying biology of rheumatic disease,” says Dr. Crow. “We’re getting new insights into what’s driving a disease and how we can use that information to ultimately improve care by identifying new biomarkers and therapeutic targets.”

Annual Report 2016

implication of diagnosis?’, ‘How does chronic illness differ from acute illness?’ Answers to these questions will provide new understanding of chronic rheumatic illnesses.”

Identifying gene transcripts to help predict an impending flare

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3.

Education Introduction

Just as patients are integral to our research process, they are also at the core of our approach to education.

Continuity of patient care in our teaching clinics by our pediatric and adult rheumatology fellows provides the essential training ground for development of a high level of expertise. Patient evaluation and management develop the humanistic qualities that form the core character traits of the most effective physicians. Our patients serve as our teachers and help to educate us about disease, but also help us to gain the maturity and sensitivity characteristic of the best clinicians.

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Education

Our faculty have deep commitments to improving the education of aspiring physicians and researchers at all levels. For example, Dr. Edward Parrish has greatly enhanced the presence of rheumatology in the Weill Cornell Medical College (WCMC) curriculum. Thanks to the efforts of Dr. Parrish and his colleagues, WCMC medical students benefit from exposure to training and patients at WCMC, New York Presbyterian Hospital, and HSS.

Increasing the prominence of rheumatology within the medical curriculum

Since 2001 Dr. Parrish has worked to establish a robust curriculum around musculoskeletal, rheumatologic, and immunologic disease, one with a focus and depth beyond that of most medical training programs. Evolving from a traditional medical school model — ​in which the first 2 years of training are primarily centered around basic science and physiology education — ​the WCMC curriculum now incorporates clinical rheumatology training in the first 2 years, with classroom work being condensed into a year and a half.

Annual Report 2016

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Alexa Adams, MD

Ed Parrish, MD

Associate Attending Pediatrician, Hospital for Special Surgery Associate Professor of Clinical Pediatrics, Weill Cornell Medical College

Assistant Attending Rheumatologist, Director, Mechanisms of Disease Course in Rheumatology, Director, Internal Medicine Residency Training Program, Hospital for Special Surgery Assistant Professor of Medicine, Weill Cornell Medical College

Our interdisciplinary approach to rheumatology education creates leaders in the field

“This is one of the things I’m very proud of,” says Dr. Parrish, “We’ve really broadened the program so rheumatology gets the recognition, time and focus that other disciplines get.”

Also unique to rheumatology education at HSS ​is our implementation of an observed structured clinical examination (OSCE) for musculoskeletal and rheumatologic disease.

Dr. Alexa Adams oversees HSS’s Pediatric Rheumatology Fellowship Program, a unique three-year program that immerses trainees in the complexities of rheumatologic illness in younger populations. The fellowship’s mission is to produce clinicians who are able to deliver high quality care to pediatric patients with rheumatologic disorders through excellence in clinical and scientific education.

Upon completion of the program, fellows have gained experience diagnosing and managing a wide range of patients. These include patients with complex multisystem conditions, such as vasculitis, lupus, and systemic arthritides. Throughout the fellowship trainees are exposed to ample inpatient and out­ patient services, consulting in the emergency room,

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Education

the intensive care unit, and on other wards. They also oversee the administration of chemo- and biologic therapies in the pediatric infusion unit.

During years 2 and 3 of their training fellows engage in a unique independent research project. Guided by a research mentor throughout, they decide on a ­clinical, basic science or translational project and see it through to, in many cases, peer-­reviewed publication. Each fellow’s research progress is overseen by the Department of Pediatrics Scholarly Oversight Committee.

A graduate of the program herself, Dr. Adams feels HSS’s pediatric rheumatology fellowship program provides trainees with a unique educational experience that sets them up to be leaders in their field.

“Our fellows benefit from the integration with our adult rheumatology training program and also the pediatric subspecialty services at New York Hospital Cornell,” she explains. “There is also their exposure and proximity to fantastic pediatric musculoskeletal care: including pediatric orthopedics, pediatric rehabilitation and musculoskeletal imaging for example.

HSS is really a terrific place to train.”

Highlights

Academy of Rheumatology Medical Educators Grant Program HSS’s Academy of Rheumatology Medical Educators, founded

by Dr. Stephen Paget and co-directed by Dr. Jessica R. Berman, is continually improving medical education around rheumatologic disease. Since the Academy was established in 2011, 21 education research grants awarded to members of the HSS-Cornell community, and totaling over $500,000, have contributed to the goal of improving education of patients and professionals.

One successful study led by Dr. Theodore R. Fields found that multidisciplinary patient education delivered by a team of rheumatologists, pharmacists, nurse educators, and social workers increased patient understanding of their disease and improved treatment adherence. The hope is that this model of care can also be applied to other complex rheumatologic disorders.

Other work being led by Dordie Moriel, RN uses interprofessional education among HSS nurses and physicians to improve the understanding of the other profession’s roles and responsibilities. The ultimate goal of the research is to develop an educational curriculum that bridges the knowledge gap between specialties in order to improve patient safety and outcomes.

Increasing the prominence of rheumatology within the medical curriculum

To improve patient education, Dr. Doruk Erkan has d ­ eveloped an iBook to help millennial patients with antiphospholipid syndrome better understand their disorder; while Drs. Juliet Aizer and Lisa Mandl have designed another digital learning tool intended to help fellows better critically appraise medical literature and evaluate published studies. The tool has been recognized by the American College of Rheumatology as a program that should be disseminated nationally.

Finally, HSS epidemiologist Dr. Carol Mancuso is designing a mentorship program that includes a curriculum to train attending physicians how best to serve as mentors to young physicians engaging in research projects. Mentoring is one of the most fundamental components of an academic institution, and Dr. Mancuso’s work will help ensure the best training and education and, ultimately, the best patient outcomes and research.

Annual Report 2016

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Professional Staff DEPARTMENT OF MEDICINE Mary K. Crow, MD Physician-in-Chief, Chair, Department of Medicine, and Chief, Rheumatology Division

Perioperative Medicine Division

Centers of Excellence

Linda A. Russell, MD Chief

Bone Health and Osteoporosis Center of Excellence

Pediatric Rheumatology Division

Linda A. Russell, MD Director

Thomas J.A. Lehman, MD Chief

Inflammatory Arthritis Center of Excellence

Rheumatology Faculty Practices

Vivian P. Bykerk, MD Director

Theodore R. Fields, MD and Jessica K. Gordon, MD Coordinators

Lupus and Antiphospholipid Syndrome Center of Excellence

Rheumatology Fellowship Program

Jane E. Salmon, MD Director

Anne R. Bass, MD Director

Scleroderma, Vasculitis, and Myositis Center of Excellence

Jessica R. Berman, MD Associate Director Alexa B. Adams, MD Director, Pediatric Rheumatology Fellowship Program Academy of Rheumatology Medical Educators Stephen A. Paget, MD Director Jessica R. Berman, MD Associate Director

Division of Rheumatology

Charles L. Christian, MD Stephen A. Paget, MD Physicians Emeriti Harry Bienenstock, MD

Robert F. Spiera, MD Director Mary Kirkland Center for Lupus Care Doruk Erkan, MD, MPH Clinical Co-Director Kyriakos A. Kirou, MD, DSc Clinical Co-Director Barbara Volcker Center for Women and Rheumatic Disease Michael D. Lockshin, MD Director

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Physicians-in-Chief Emeriti

Professional Staff

Lawrence J. Kagen, MD Irwin Nydick, MD Martin Nydick, MD Ernest Schwartz, MD

Medical Staff Attending Physicians Richard S. Bockman, MD, PhD Director, Endocrinology Barry D. Brause, MD Director, Infectious Disease Mary K. Crow, MD Physician-in-Chief Theodore R. Fields, MD Allan Gibofsky, MD, JD Lionel B. Ivashkiv, MD Chief Scientific Officer Thomas J.A. Lehman, MD Chief, Pediatric Rheumatology Michael D. Lockshin, MD C. Ronald MacKenzie, MD Steven K. Magid, MD

Carol A. Mancuso, MD Joseph A. Markenson, MD Stephen A. Paget, MD Jane E. Salmon, MD James P. Smith, MD Pulmonary Medicine Robert F. Spiera, MD Associate Attending Physicians Alexa B. Adams, MD Pediatric Rheumatology Anne R. Bass, MD Jessica R. Berman, MD Vivian P. Bykerk, MD Lisa R. Callahan, MD Primary Care Sports Medicine

Trang M. Bui, MD, MPH Perioperative Medicine

Andrew O. Miller, MD Infectious Disease

Assistant Attending Physicians

James J. Calloway III, MD Perioperative Medicine

Mitchell Nelson, MD Perioperative Medicine

Susan B. Bostwick, MD Pediatrics

Hyun Susan Cha, MD Pediatrics

Nancy Pan, MD Pediatric Rheumatology

Michael S. Farber, MD

Karmela K. Chan, MD

Edward J. Parrish, MD

Chad M. Craig, MD Perioperative Medicine

Stephanie L. Perlman, MD Pediatrics

Mary F. DiMaio, MD Pediatrics

Linda A. Russell, MD Chief, Perioperative Medicine

Obinna D. Eneanya, MD Perioperative Medicine

Romona D. Satchi, MD Perioperative Medicine

David R. Fernandez, MD, PhD

Magdalena E. Swierczewski, MD Perioperative Medicine

Kenton H. Fibel, MD Primary Care Sports Medicine

Sarah F. Taber, MD Pediatric Rheumatology

Jacobo Futran, MD Michael I. Jacobs, MD Dermatology Bento R. Mascarenhas, MD Lakshmi Nandini Moorthy, MD Pediatric Rheumatology Thomas M. Novella, DPM Podiatric Medicine Dana E. Orange, MD Alana C. Serota, MD Endocrinology

Doruk Erkan, MD, MPH

Marci A. Goolsby, MD Primary Care Sports Medicine

Susan M. Goodman, MD

Jessica K. Gordon, MD

Brian C. Halpern, MD Director, Primary Care Sports Medicine

Michael W. Henry, MD Infectious Disease

David A. Wang, MD Primary Care Sports Medicine

Fellows in Rheumatology

Miriam B. Hoffman, MD Perioperative Medicine

Hendricks H. Whitman III, MD

Karima Becetti, MD

Dee Dee Wu, MD

Jonathan Cheah, MD

Arthur M.F. Yee, MD, PhD

Karim Ladak, MD

Christine M. Yu, MD Perioperative Medicine

Sarah Lieber, MD

Lisa S. Ipp, MD Chief, Pediatrics Jordan D. Metzl, MD Primary Care Sports Medicine Lisa R. Sammaritano, MD Sergio Schwartzman, MD Emily M. Stein, MD, MSc Endocrinology Assistant Attending Physicians Juliet B. Aizer, MD, MPH Dalit Ashany, MD Laura V. Barinstein, MD Pediatric Rheumatology John W. Barnhill, MD Director, Psychiatry Service Jennifer M. Berger, MD Perioperative Medicine William W. Briner, Jr., MD Primary Care Sports Medicine Matthew L. Buchalter, MD Perioperative Medicine

Wesley Hollomon, MD Perioperative Medicine George D. Kalliolias, MD, PhD Shanthini Kasturi, MD, MSc James J. Kinderknecht, MD Primary Care Sports Medicine Osric S. King, MD Primary Care Sports Medicine Kyriakos A. Kirou, MD, DSc Mary J. Kollakuzhiyil, MD Perioperative Medicine David A. Kuppersmith, MD Perioperative Medicine Lindsay S. Lally, MD Geeta Laud, MD Perioperative Medicine Lawrence F. Levin, MD Director, Cardiovascular Disease Alana B. Levine, MD Lisa A. Mandl, MD, MPH

Brett G. Toresdahl, MD Primary Care Sports Medicine

Florence Yu, MD Perioperative Medicine Jennie Yu, MD Perioperative Medicine

Ariel D. Teitel, MD Mary Beth Walsh, MD

Fardina Malik, MD Bella Mehta, MD Nino Mikaberidze, MD Noa Schwartz, MD Kai Sun, MD

Voluntary and Affiliated Medical Staff

Fellows in Pediatric Rheumatology

Attending Physician

Natalie Rosenwasser, MD

Harry Spiera, MD

Salma Siddique, MD

Associate Attending Physicians Jessica G. Davis, MD Pediatrics, Genetics Gail E. Solomon, MD Pediatrics, Neurology Richard Stern, MD

Gabriella Safdieh, MD Rebecca Trachtman, MD Erin Treemarcki, MD

Fellow in Primary Care Sports Medicine Justin Conway, MD

Charis Meng, MD

Annual Report 2016

19

Allied Health Professionals

Research Staff

Nursing

Lionel B. Ivashkiv, MD Chief Scientific Officer

Tricia Dougherty, RN Patient Care Director

Leadership

Named Chairs and Professorships Michael R. Bloomberg Chair in Autoimmune Disease

Linda Leff, RN, BSN, BC Director, Infusion Unit

Robert N. Hotchkiss, MD Director of Clinical Research and Chief Innovation Officer

Psychiatry

Senior Scientists

Franchellie M. Cadwell Chair

Julia M. Kim, PhD Clinical Psychology

Franck J. Barrat, PhD

Sergio Schwartzman, MD

Social Work Adena Batterman, MSW, LCSW

Carl P. Blobel, MD, PhD Adele L. Boskey, PhD Mary K. Crow, MD Mary B. Goldring, PhD

Franck J. Barrat, PhD

Alessandra B. Pernis, MD

Roberta Horton, LCSW, ACSW

Jane E. Salmon, MD

Jane E. Salmon, MD

Associate Scientists Theresa T. Lu, MD, PhD

David H. Koch Chair for Arthritis and Tissue Degeneration Research

Emily Reiss, LMSW

Stephen Lyman, PhD

Lionel B. Ivashkiv, MD

Albairis Rosa, LMSW

Inez Rogatsky, PhD

Amy Silverman, LCSW Priscilla Toral, LCSW My-Lan Tran, LCSW Joan Westreich, LCSW

Chitra Dahia, PhD Xiaoyu Hu, MD, PhD Kyriakos A. Kirou, MD, DSc Kyung-Hun Park Min, PhD Xiaoping Qing, PhD Baohong Zhao, PhD Mary Kirkland Center for Lupus Research Investigators

C. Ronald MacKenzie, MD, Chair in Ethics and Medicine C. Ronald MacKenzie, MD Richard L. Menschel Research Chair Lionel B. Ivashkiv, MD Stephen A. Paget, MD, Chair in Rheumatology Stephen A. Paget, MD

Mary K. Crow, MD

Benjamin M. Rosen Chair in Immunology and Inflammation Research

Theresa T. Lu, MD, PhD

Mary K. Crow, MD

Alessandra B. Pernis, MD

Joseph P. Routh Professor of Rheumatic Diseases in Medicine

Franck J. Barrat, PhD

Jane E. Salmon, MD

Mary K. Crow, MD Virginia F. and William R. Salomon Chair in Musculoskeletal Research Carl P. Blobel, MD, PhD

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Division of Rheumatology

Starr Chair in Tissue Engineering Research supporting Chitra Dahia, PhD

supporting Suzanne A. Maher, PhD

Melissa Flores, LMSW

Assistant Scientists

supporting Theresa T. Lu, MD, PhD

Linda A. Russell, MD Collette Kean Research Chair

Mavis Seehaus, MS, LCSW

St. Giles Research Chair

Russell F. Warren Research Chair

Lionel B. Ivashkiv, MD

Jillian Rose, LCSW

Alessandra B. Pernis, MD

The Anne and Joel Ehrenkranz Chair in Perioperative Medicine

Suzan Fischbein, LMSW

Juliette Kleinman, LCSW, ACSW

Peter J. Sharp Chair in Lupus Research

Professional Staff

Named Fellowships Charles L. Christian Research Fellowship Marie-Dominique Ah-Kioon, PhD Ira W. DeCamp Fellowship in Musculoskeletal Genetics Mary B. Goldring, PhD Robert and Gillian Steel Fellowship in Musculoskeletal Research Inez Rogatsky, PhD Immunology and Inflammation Fellowship Sergei Rudchenko, PhD Michael D. Lockshin Fellowship of the Barbara Volcker Center for Women and Rheumatic Disease Xiaoping Qing, MD, PhD Shanthini Kasturi, MD, MSc

Selected Notable Publications Nov. 2015 to Nov. 2016 (bold indicates HSS Rheumatology or Rheumatology Research Faculty)

Alabi RO, Glomski K, Haxaire C, Weskamp G, Monette S, Blobel CP. A DAM10-­ ­ d ependent signaling through Notch1 and Notch4 controls development of organ-­specific vascular beds. Circ Res. 2016 Aug 5;119(4):519-31.

Altman R, Hochberg M, Gibofsky A, Jaros M, Young C. Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: a 12-week, phase 3 study. Curr Med Res Opin.

2015 Dec;31(12):2331-43.

Arkema EV, Askling J, Salmon JE, Simard JF. Sex ratio of offspring born to women with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheumatol. 2016 Aug 26. doi: 10.1002/ art.39843. [Epub ahead of print] Arkema EV, Palmsten K, Sjöwall C, Svenungsson E, Salmon JE, Simard JF. What to expect when expecting with systemic lupus erythematosus (SLE): A ­population-based study of maternal and fetal outcomes in SLE and pre-SLE. Arthritis Care Res (Hoboken).

2016 Jul;68(7):988-94.

Barbhaiya M, Andrade D, Erkan D; APS ACTION. AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Net­ working (APS ACTION): 5-year update. Curr Rheumatol Rep. 2016 Oct;18(10):64.

Barrat FJ, Elkon KB, Fitzgerald KA. Importance of nucleic acid recognition in inflammation and autoimmunity. Annu Rev Med. 2016;67:323-36.

Bartlett SJ, Bykerk VP, Cooksey R, Choy EH, Alten R, Christensen R, Furst DE, Guillemin F, Halls S, Hewlett S, Leong AL, Lyddiatt A, March L, Montie P, Orbai AM, Pohl C, Voshaar MS, Woodworth TG, Bingham CO 3rd. Feasibility and domain validation of rheumatoid arthritis (RA) flare core domain set: Report of the OMERACT 2014 RA Flare Group Plenary. J Rheumatol. 2015 Nov;42(11):2185-9.

Berman JR, Aizer J, Bass AR, Blanco I, Davidson A, Dwyer E, Fields TR, Huang WT, Kang JS, Kerr LD, ­Krasnokutsky-­Samuels S, Lazaro DM, ­Schwartzman-­Morris JS, Paget SA, Pillinger MH. Fellow use of medical jargon correlates inversely with patient and observer perceptions of professionalism: results of a rheumatology OSCE (ROSCE) using challenging patient scenarios. Clin Rheumatol.

2016 Aug;35(8):2093-9.

Annual Report 2016

Berman JR, O’Rourke KS, Kolasinski SL, Aizer J, Wheatley MJ, Battistone MJ, Siaton BC, ­Criscione-­S chreiber L, Pillinger MH, Lazaro DM. Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen years promoting rheumatology educators and education. Arthritis Care Res (Hoboken). 2016 Nov;68(11):1591-1597.

Blachère NE, Parveen S, Fak J, Frank MO, Orange DE. Inflammatory but not apoptotic death of granulocytes citrullinates fibrinogen.

Arthritis Res Ther. 2015 Dec 17;17:369.

Blobel CP, Haxaire C, Kalliolias GD, DiCarlo E, Salmon J, Srivastava A. Blood-­induced arthropathy in hemophilia: mechanisms and ­heterogeneity. Semin Thromb Hemost. 2015 Nov;41(8):832-7.

Bykerk VP, Bingham CO, Choy EH, Lin D, Alten R, Christensen R, Furst DE, Hewlett S, Leong A, March L, Woodworth T, Boire G, Haraoui B, Hitchon C, Jamal S, Keystone EC, Pope J, Tin D, Thorne JC, Bartlett SJ. Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set. RMD Open. 2016 May 26;2(1):e000225. ­ artin-Ceba R, Indrakanti D, Specks U, Stone JH, Hoffman GS, C Kallenberg CG, Langford CA, Merkel PA, Spiera RF, Monach PA, St. Clair W, Seo P, Tchao NK, Ytterberg SR, Brunetta PG, Song H, Birmingham D, Rovin BH; RAVE-ITN Research Group. The pharmacogenomic association of Fcγ receptors and cytochrome p450 enzymes and response to treatment with rituximab or cyclophosphamide in anti-­neutrophil cytoplasmic ­antibody-­associated v asculitis. Arthritis Rheumatol. 2016 Aug 2. doi: 10.1002/​ ­ art.39822. [Epub ahead of print] Chandrasekaran U, Yi W, Gupta S, Weng CH, Giannopoulou E, Chinenov Y, Jessberger R, Weaver CT, Bhagat G, Pernis AB. Regulation of effector Treg cells in murine lupus. Arthritis Rheumatol. 2016 Jun;68(6):1454-66.

Chia JJ, Lu TT. Update on macrophages and innate immunity in scleroderma. Curr Opin Rheumatol. 2015 Nov;27(6):530-6.

Chia JJ, Zhu T, Chyou S, Dasoveanu DC, Carballo C, Tian S, Magro CM, Rodeo S, Spiera RF, Ruddle NH, McGraw TE, Browning JL, Lafyatis R, Gordon JK, Lu TT. Dendritic cells maintain dermal ­adipose-­derived stromal cells in skin fibrosis. J Clin Invest. 2016 Nov 1;126(11):4331-4345.

21

Coates LC, Kavanaugh A, Mease PJ, — Schwartzman S, ­Siegel EL, Toloza S, Tuong W, Ritchlin CT. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment recommendations for psoriatic arthritis. Arthritis Rheumatol. 2016 May;68(5):1060-71.

Cody EA, Mancuso CA, MacMahon A, Marinescu A, Burket JC, Drakos MC, Roberts MM, Ellis SJ. Development of an expectations survey for patients undergoing foot and ankle surgery. Foot Ankle Int. 2016 Sep 20. pii: 1071100716666260. [Epub ahead of print] Crow MK. Autoimmunity: Interferon α or β: which is the culprit in autoimmune disease? Nat Rev Rheumatol. 2016 Aug;12(8):43940. doi: 10.1038/nrrheum.2016.117. No abstract available.

Curtis JR, Bykerk VP, Aassi M, Schiff M. Adherence and persistence with methotrexate in rheumatoid arthritis: A systematic review. J Rheumatol. 2016 Nov;43(11):1997-2009.

Dasoveanu DC, Shipman WD, Chia JJ, Chyou S, Lu TT. Regulation of lymph node ­vascular-­stromal compartment by dendritic cells.

Trends Immunol. 2016 Sep 13.

Ekholm L, Vosslamber S, Tjärnlund A, de Jong TD, Betteridge Z, McHugh N, Plestilova L, Klein M, Padyukov L, Voskuyl AE, Bultink IE, Michiel Pegtel D, Mavragani CP, Crow MK, Vencovsky J, Lundberg IE, Verweij CL. Autoantibody specificities and type I interferon pathway activation in idiopathic inflammatory myopathies. Scand J Immunol. 2016 Aug;84(2):100-9. doi: 10.1111/ sji.12449.

Emery P, Bingham CO 3rd, Burmester GR, Bykerk VP, Furst DE, Mariette X, van der Heijde D, van Vollenhoven R, Arendt C, Mountian I, Purcaru O, Tatla D, VanLunen B, Weinblatt ME. Certolizumab pegol in combination with dose-­optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, ­double-blind, ­placebo-­controlled phase III study.

Ann Rheum Dis. 2016 May 10. pii: ­annrheumdis-2015-­209057.

Fang C, Qiao Y, Mun SH, Lee MJ, Murata K, Bae S, Zhao B, ParkMin KH, Ivashkiv LB. Cutting Edge: EZH2 promotes osteoclastogenesis by epigenetic silencing of the negative regulator IRF8. J Immunol. 2016 Jun 1;196(11):4452-6.

Fein AW, Figgie CA, Dodds TR, ­Wright-­Chisem J, Parks ML, Mandl LA, Su EP, Salmon JE, Mayman DJ, Lee YY, Figgie MP, Goodman SM. Systemic lupus erythematosus does not increase risk of adverse events in the first 6 months after total knee arthroplasty. J Clin Rheumatol. 2016 Oct;22(7):355-9.

Fernandez D, Kirou KA. What causes lupus flares? Curr Rheumatol Rep. 2016 Mar;18(3):14.

Fleischmann R, Mease PJ, Schwartzman S, Hwang LJ, Soma K, Connell CA, Takiya L, Bananis E. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group. Clin Rheumatol. 2016 Oct 12. [Epub ahead of print] Fussner LA, Hummel AM, Schroeder DR, Silva F, C ­ artin-Ceba R, Snyder MR, Hoffman GS, Kallenberg CG, Langford CA, Merkel PA, Monach PA, Seo P, Spiera RF, William St. Clair E, Tchao NK, Stone JH, Specks U. Rituximab in ANCA-­Associated ­Vasculitis-­Immune Tolerance Network Research Group. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol. 2016 Jul;68(7):1700-10.

Gerosa M, Meroni PL, Erkan D. Recognition and management of antiphospholipid syndrome. Curr Opin Rheumatol. 2016 Jan;​ 28(1):51-9.

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Division of Rheumatology

Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: structure, function and c ­ artilage-bone crosstalk. Nat Rev Rheumatol. 2016 Nov;12(11):632-644.

Goodman SM, Johnson B, Zhang M, Huang WT, Zhu R, Figgie M, Alexiades M, Mandl LA. Patients with rheumatoid arthritis have similar excellent outcomes after total knee replacement compared with patients with osteoarthritis. J Rheumatol. 2016 Jan;43(1):46-53.

Goodman SM, Mandl LA, Parks ML, Zhang M, McHugh KR, Lee YY, Nguyen JT, Russell LA, Bogardus MH, Figgie MP, Bass AR. Disparities in TKA outcomes: Census tract data show interactions between race and poverty. Clin Orthop Relat Res. 2016 Sep;474(9):1986-95.

Goodman SM, Menon I, Christos PJ, Smethurst R, Bykerk VP. Management of perioperative tumour necrosis factor α inhibitors in rheumatoid arthritis patients undergoing arthroplasty: a systematic review and meta-­analysis. Rheumatology (Oxford). 2016 Mar;55(3):573-82.

Goodman SM, Parks ML, McHugh K, Fields K, Smethurst R, Figgie MP, Bass AR. Disparities in outcomes for African Americans and whites undergoing total knee arthroplasty: A systematic literature review. J Rheumatol. 2016 Apr;43(4):765-70.

Gordon JK, Domsic RT. Clinical trial design issues in systemic ­sclerosis: an update. Curr Rheumatol Rep. 2016 Jun;18(6):38.

Hazlewood GS, Thorne JC, Pope JE, Lin D, Tin D, Boire G, Haraoui B, Hitchon CA, Keystone EC, Jamal S, Bykerk VP; CATCH Investigators. The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis. Ann Rheum Dis. 2016 Jun;75(6):1003-8.

Hitchon CA, Boire G, Haraoui B, Keystone E, Pope J, Jamal S, Tin D, Thorne C, Bykerk VP; CATCH investigators. Self-­reported comorbidity is common in early inflammatory arthritis and associated with poorer function and worse arthritis disease outcomes: results from the Canadian Early Arthritis Cohort. Rheumatology (Oxford).

2016 Oct;55(10):1751-62.

Huynh L, Kusnadi A, Park SH, Murata K, Park-Min KH, Ivashkiv LB. Opposing regulation of the late phase TNF response by ­mTORC1-IL-10 signaling and hypoxia in human macrophages. Sci Rep. 2016 Aug 25;6:31959.

Hyun G, Li J, Bass AR, Mohapatra A, Woller SC, Lin H, Eby C, McMillin GA, Gage BF. Use of signals and systems engineering to improve the safety of warfarin initiation. J Thromb Thrombolysis.

2016 Nov;42(4):529-33.

Johnson ME, Grassetti AV, Taroni JN, Lyons SM, Schweppe D, Gordon JK, Spiera RF, Lafyatis R, Anderson PJ, Gerber SA, Whitfield ML. Stress granules and RNA processing bodies are novel autoantibody targets in systemic sclerosis. Arthritis Res Ther. 2016 Jan 22;18:27.

Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2016 Jan;12(1):49-62.

Kang L, Hashmi SZ, Nguyen J, Lee SK, Weiland AJ, Mancuso CA. Patients with thumb carpometacarpal arthritis have quantifiable characteristic expectations that can be measured with a survey.

Clin Orthop Relat Res. 2016 Jan;474(1):213-21.

Kasturi S, Sammaritano LR. Corticosteroids in lupus. Rheum Dis Clin North Am. 2016 Feb;42(1):47-62.

Selected Notable Publications

Kaul A, Gordon C, Crow MK, Touma Z, Urowitz MB, van Vollenhoven R, Ruiz-­Irastorza G, Hughes G. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016 Jun 16;2:16039. doi: 10.1038/nrdp.2016.39.

Kim MY, Buyon JP, Guerra MM, Rana S, Zhang D, Laskin CA, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Porter TF, Merrill JT, Stephenson MD, Gao Q, Karumanchi SA, Salmon JE. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol. 2016 Jan;214(1):108. e1-108.e14.

Kozora E, Ulug ˘ AM, Erkan D, Vo A, Filley CM, Ramon G, Burleson A, Zimmerman R, Lockshin MD. Functional magnetic resonance imaging of working memory and executive dysfunction in systemic lupus erythematosus and antiphospholipid a ­ ntibody-­p ositive patients. Arthritis Care Res (Hoboken). 2016 Nov;68(11):1655-1663.

Lally L, Forbess L, Hatzis C, Spiera R. Brief Report: A prospective open-label phase IIa trial of tocilizumab in the treatment of poly­ myalgia rheumatica. Arthritis Rheumatol. 2016 Oct;68(10):2550-4.

Lally L, Spiera R. B-cell-­targeted therapy in systemic vasculitis.

Curr Opin Rheumatol. 2016 Jan;28(1):15-20.

Lee MJ, Lim E, Mun SH, Bae S, Murata K, Ivashkiv LB, Park-Min KH. Intravenous immunoglobulin (IVIG) attenuates TNF-­induced pathologic bone resorption and suppresses osteoclastogenesis by inducing A20 expression. J Cell Physiol. 2016 Feb;231(2):449-58.

Lee Y, Wakita D, Dagvadorj J, Shimada K, Chen S, Huang G, Lehman TJ, Fishbein MC, Hoffman HM, Crother TR, Arditi M. IL-1 Signaling Is Critically Required in Stromal Cells in Kawasaki Disease Vasculitis Mouse Model: Role of Both IL-1α and IL-1β. Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2605-16.

MacKenzie CR, Goodman SM. Stress dose steroids: myths and perioperative medicine. Curr Rheumatol Rep. 2016 Jul;18(7):47.

Mancuso CA, Duculan R, Cammisa FP, Sama AA, Hughes AP, Lebl DR, Girardi FP. Fulfillment of patients’ expectations of lumbar and cervical spine surgery. Spine J. 2016 Oct;16(10):1167-1174.

Mancuso CA, Duculan R, Girardi FP. Healthy physical activity levels below recommended thresholds two years after lumbar spine surgery. Spine (Phila Pa 1976). 2016 Jun 29. [Epub ahead of print] Mancuso CA, Duculan R, Cammisa FP, Sama AA, Hughes AP, Lebl DR, Girardi FP. Proportion of expectations fulfilled: A new method to report p ­ atient-­centered outcomes of spine surgery. Spine (Phila Pa 1976). 2016 Jun;41(11):963-70.

Mancuso CA, Lee SK, Dy CJ, Landers ZA, Model Z, Wolfe SW. Expectations and limitations due to brachial plexus injury: a qualitative study. Hand (N Y). 2015 Dec;10(4):741-9.

Mancuso CA, Reid MC, Duculan R, Girardi FP. Improvement in pain after lumbar spine surgery: The role of preoperative expectations of pain relief. Clin J Pain. 2016 Mar 28. [Epub ahead of print] Mandl LA, Zhu R, Huang WT, Zhang M, Alexiades MM, Figgie MP, Goodman SM. Short-term total hip arthroplasty outcomes in patients with psoriatic arthritis or psoriatic skin disease compared to patients with osteoarthritis. Arthritis Rheumatol. 2016 Feb;68(2):410-7.

Manni M, Gupta S, Nixon BG, Weaver CT, Jessberger R, Pernis AB. IRF4-­dependent and IRF4-­independent pathways contribute to DC dysfunction in lupus. PLoS One. 2015 Nov 6;10(11):e0141927. ­ artel-­Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper M C, Goldring MB, Goldring SR, Jones G, Teichtahl AJ, Pelletier JP. Osteoarthritis. Nat Rev Dis Primers. 2016 Oct 13;2:16072.

Annual Report 2016

Mavragani CP, Sagalovskiy I, Guo Q, Nezos A, Kapsogeorgou EK, Lu P, Liang Zhou J, Kirou KA, Seshan SV, Moutsopoulos HM, Crow MK. Expression of long interspersed nuclear element 1 retro­elements and induction of type I interferon in patients with systemic autoimmune disease. Arthritis Rheumatol. 2016 Nov;68(11):2686-2696. doi: 10.1002/art.39795.

Math KR, Berkowitz JL, Paget SA, Endo Y. Imaging of musculoskeletal infection. Rheum Dis Clin North Am. 2016 Nov;42(4):769-784.

Miller CH, Smith SM, Elguindy M, Zhang T, Xiang JZ, Hu X, Ivashkiv LB, Zhao B. RBP-J-­regulated miR-182 promotes TNF-α-­induced osteoclastogenesis. J Immunol. 2016 Jun 15;196(12):4977-86.

Miloslavsky EM, Lu N, Unizony S, Choi HK, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St. Clair EW, Tchao NK, Fervenza F, Monach PA, Specks U, Stone JH. ­M yeloperoxidase-ANCA-­p ositive and ANCA-­n egative patients with granulomatosis with polyangiitis: Distinct patient subsets.

Arthritis Rheumatol. 2016 Jul 18. doi: 10.1002/art.39812. [Epub ahead of print] Mineo C, Lanier L, Jung E, Sengupta S, Ulrich V, Sacharidou A, Tarango C, Osunbunmi O, Shen YM, Salmon JE, Brekken RA, Huang X, Thorpe PE, Shaul PW. Identification of a monoclonal antibody that attenuates antiphospholipid s ­ yndrome-­related pregnancy complications and thrombosis. PLoS One. 2016 Jul 27;11(7):e0158757 Moorthy LN, Baldino ME, Kurra V, Puwar D, Llanos A, Peterson MG, Hassett AL, Lehman TJ; International SMILEY© Collaborative group. Relationship between ­health-­related quality of life, disease activity and disease damage in a prospective international multicenter cohort of childhood onset systemic lupus erythematosus patients. Lupus. 2016 Aug 5. pii: 0961203316659546. [Epub ahead of print] Nuruzzaman F, Sherman Y, Ostfeld BM, Adams AB, Pan N, Barinstein LV, Lehman TJ, Moorthy LN. Simple screening tool for assessing attention deficit in pediatric lupus. Lupus. 2016 Apr;25(4):447-8.

Nusbaum JS, Gordon JK, Steen VD. African American race associated with body image dissatisfaction among patients with systemic sclerosis. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):70-73.

Olferiev M, Jacek E, Kirou KA, Crow MK. Novel molecular signatures in mononuclear cell populations from patients with systemic lupus erythematosus. Clin Immunol. 2016 Aug 26. pii: S15216616(16)30311-4. doi: 10.1016/j.clim.2016.08.018. [Epub ahead of print] Otero M, Peng H El Hachem K, Culley KL, Wondimu EB, Quinn J, Asahara H, Tsuchimochi K, Hashimoto K, Goldring MB. ELF3 modulates type II collagen gene (COL2A1) transcription in chondrocytes by inhibiting SOX9-CBP/p300-­d riven histone acetyltransferase activity. Connect Tissue Res. 2016 Jun 16:1-12.

Park-Min KH. Epigenetic regulation of bone cells. Connect Tissue Res. 2016 Apr 14:1-15.

Pelrine ER, Ah-Kioon MD, Zhang M, Barrat FJ, Spiera RF, Gordon JK. Musculoskeletal involvement in SSc is associated with worse scores on Short Form-36 and Scleroderma Health Assessment Questionnaire and lower tumor necrosis ­factor-α gene expression in peripheral blood mononuclear cells. HSS J. 2016 Oct;12(3):255-260.

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Pepper RJ, Draibe JB, Caplin B, Fervenza FC, Hoffman GS, Kallenberg CG, Langford CA, Monach PA, Seo P, Spiera R, St. Clair EW, Tchao NK, Stone JH, Specks U, Merkel PA, Salama AD; RAVE-ITN Research Group. The association of serum calprotectin (S100A8/S100A9) levels with disease relapses in PR3ANCA-­associated vasculitis. Arthritis Rheumatol. 2016 Jul 18. doi: 10.1002/art.39814. [Epub ahead of print] Pernis AB, Ricker E, Weng CH, Rozo C, Yi W. Rho kinases in auto­ immune diseases. Annu Rev Med. 2016;67:355-74.

Peterfy C, Burmester GR, Bykerk VP, Combe BG, DiCarlo JC, Furst DE, Huizinga TW, Wong DA, Conaghan PG, Emery P. Sustained improvements in MRI outcomes with abatacept following the ­withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1501-5.

Qiao Y, Kang K, Giannopoulou E, Fang C, Ivashkiv LB. IFN-γ induces histone 3 lysine 27 trimethylation in a small subset of promoters to stably silence gene expression in human macrophages. Cell Rep. 2016 Sep 20;16(12):3121-9.

Qing X, D Rogers L, Mortha A, Lavin Y, Redecha P, Issuree PD, Maretzky T, Merad M, R McIlwain D, Mak TW, Overall CM, Blobel CP, Salmon JE. iRhom2 regulates CSF1R cell surface expression and non-­steady state myelopoiesis in mice. Eur J Immunol. 2016 Sep 7. doi: 10.1002/eji.201646482. [Epub ahead of print] Rice LM, Padilla CM, McLaughlin SR, Mathes A, Ziemek J, Goummih S, Nakerakanti S, York M, Farina G, Whitfield ML, Spiera RF, Christmann RB, Gordon JK, Weinberg J, Simms RW, Lafyatis R. Fresolimumab treatment decreases biomarkers and improves ­clinical symptoms in systemic sclerosis patients. J Clin Invest.

2015 Jul 1;125(7):2795-807.

Rice LM, Ziemek J, Stratton EA, McLaughlin SR, Padilla CM, Mathes AL, Christmann RB, Stifano G, Browning JL, Whitfield ML, Spiera RF, Gordon JK, Simms RW, Zhang Y, Lafyatis R. A longitudinal biomarker for the extent of skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheumatol. 2015 Nov;67(11):3004-15.

Ricker E, Chowdhury L, Yi W, Pernis AB. The RhoA-ROCK pathway in the regulation of T and B cell responses. F1000Res. 2016 Sep 12;5.

Rivas MN, Lee Y, Wakita D, Chiba N, Dagvadorj J, Shimada K, Chen S, Fishbein MC, Lehman TJ, Crother TR, Arditi M.CD8+ T cells contribute to the development of coronary arteritis in the Lactobacillus casei ­extract-­induced murine model of Kawasaki Disease. Arthritis Rheumatol. 2016 Oct 1. doi: 10.1002/art.39939. [Epub ahead of print] Roberts JE, Mandl LA, Su EP, Mayman DJ, Figgie MP, Fein AW, Lee YY, Shah U, Goodman SM. Patients with systemic lupus erythematosus have increased risk of short-term adverse events after total hip arthroplasty. J Rheumatol. 2016 Aug;43(8):1498-502 ­ odríguez-Pintó I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, R Espinosa G, Cervera R; CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016 Sep 15.

Sammaritano LR. Management of systemic lupus erythematosus during pregnancy. Annu Rev Med. 2016 Sep 21. [Epub ahead of print]

24

Division of Rheumatology

Sciascia S, Baldovino S, Schreiber K, Solfietti L, Radin M, Cuadrado MJ, Menegatti E, Erkan D, Roccatello D. Thrombotic risk assessment in antiphospholipid syndrome: the role of new antibody specificities and thrombin generation assay. Clin Mol Allergy. 2016 Jul 15;14:6.

Shah AA, Schiopu E, Chatterjee S, Csuka ME, Frech T, Goldberg A, Spiera R, Peng SL, McBride RJ, Cleveland JM, Steen V. The recurrence of digital ulcers in patients with systemic sclerosis after discontinuation of oral treprostinil. J Rheumatol. 2016 Sep;43(9):1665-71.

Taraborelli M, Leuenberger L, Lazzaroni MG, Martinazzi N, Zhang W, Franceschini F, Salmon J, Tincani A, Erkan D. The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus. Lupus. 2016 Oct;25(12):1365-8.

Ulrich V, Gelber SE, Vukelic M, Sacharidou A, Herz J, Urbanus RT, de Groot PG, Natale DR, Harihara A, Redecha P, Abrahams VM, Shaul PW, Salmon JE, Mineo C. ApoE receptor 2 mediation of ­trophoblast dysfunction and pregnancy complications induced by antiphospholipid antibodies in mice. Arthritis Rheumatol. 2016 Mar;68(3):730-9.

Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CM, St. Clair EW, Ikle D, Tchao NK, Ding L, Brunetta P, Choi HK, Monach PA, Fervenza F, Stone JH, Specks U; RAVE-ITN Research Group. Clinical outcomes of treatment of anti-­n eutrophil cytoplasmic antibody (ANCA)-­ associated vasculitis based on ANCA type. Ann Rheum Dis. 2016 Jun;75(6):1166-9. Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol.

2016 Jun;3(2):75-84.

Urban MK, ­Mangini-­Vendel M, Lyman S, Pan TJ, Magid SK. The need for a step-up in postoperative medical care is predictable in orthopedic patients undergoing elective surgery. HSS J. 2016 Feb;12(1):59-65 Walters HM, Pan N, Lehman TJ, Adams A, Kalliolias GD, Zhu YS, Santiago F, Nguyen J6, Sitaras L, C ­ unningham-­Rundles S, Walsh TJ, Toussi SS. The impact of disease activity and tumour necrosis ­factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis. Clin Exp Immunol. 2016 Jun;184(3):308-17.

Weng CH, Gupta S, Geraghty P, Foronjy R, Pernis AB. Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production. Mol Immunol. 2016 Mar;71:115-22.

Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-­positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016 Jan 12;3(1):e000131.

Yelnik CM, Porter TF, Branch DW, Laskin CA, Merrill JT, Guerra MM, Lockshin MD, Buyon JP, Petri M, Sammaritano LR, Stephenson MD, Kim MY, Salmon JE. Brief Report: changes in antiphospholipid antibody titers during pregnancy: Effects on pregnancy outcomes.

Arthritis Rheumatol. 2016 Aug;68(8):1964-9.

Yelnik CM, Richey M, Haiduc V, Everett S, Zhang M, Erkan D. Cardiovascular Disease Prevention Counseling Program for Systemic Lupus Erythematosus Patients. Arthritis Care Res (Hoboken). 2016 Oct 16. doi: 10.1002/acr.23128. [Epub ahead of print]

Selected Notable Publications

HSS Contact Information Hospital for Special Surgery

Rheumatology Fellowship Program

Mary K. Crow MD Physician-in-Chief and Chair, Department of Medicine, Chief of the Division of Rheumatology and the Benjamin M. Rosen Chair in Immunology and Inflammation Research 212.606.1397

Anne R. Bass, MD Director 212.774.2189 Pediatric Rheumatology Fellowship Program

Lupus and Antiphospholipid Syndrome Jane E. Salmon, MD Director 212.606.1422 Scleroderma, Vasculitis & Myositis

Perioperative Medicine Division

Alexa B. Adams, MD Director 212.774.2083

Robert F. Spiera, MD Director 212.774.2048

Linda A. Russell, MD Director 212.606.1305

HSS Academy of Rheumatology Medical Educators

Mary Kirkland Center for Lupus Care

Pediatric Rheumatology Division Thomas J.A. Lehman, MD Chief 212.606.1151 Rheumatology Faculty Practices Theodore R. Fields, MD Co-Coordinator 212.606.1286 Jessica K. Gordon, MD Co-Coordinator 212.606.1173

Stephen A. Paget, MD Director 212.606.1845

Centers of Excellence

Doruk Erkan, MD, MPH Clinical Co-Director 212.774.2291 Kyriakos A. Kirou, MD, DSc Clinical Co-Director 212.606.1728

Bone Health and Osteoporosis

Barbara Volcker Center for Women and Rheumatic Disease

Linda A. Russell, MD Director 212.606.1305

Michael D. Lockshin, MD Director 212.606.1461

Inflammatory Arthritis Vivian P. Bykerk, MD Director 212.774.7520

Officers Chair Kendrick R. Wilson III Vice Chair Michael Esposito Thomas Lister Deirdre Stanley President and Chief Executive Officer Louis A. Shapiro

Surgeon-in-Chief and Medical Director

Executive Vice President, Chief Legal Officer and Secretary

Todd J. Albert, MD

Irene Koch, Esq.

Executive Vice President and Chief Operating Officer

Chairmen, Emeriti

Lisa A. Goldstein

Dean R. O’Hare

Executive Vice President and Chief Financial Officer

Aldo Papone

Stacey L. Malakoff

About HSS

Design by Addison www.addison.com

HSS is the world’s largest academic medical center focused on musculoskeletal health.

The mission of Hospital for Special Surgery is to provide the highest-quality patient care; improve mobility; enhance the quality of life for all; and advance the science of orthopaedic surgery, rheumatology, and their related disciplines through research and education.

With the largest group of rheumatologists in the country, HSS is a world leader in the research and treatment of rheumatic disease. Our Centers of Excellence are multidisciplinary and innovative programs, established by our expert faculty with the goal of improving the lives of patients with chronic musculoskeletal, autoimmune and inflammatory diseases.

Rheumatologists at HSS see a high volume of patients as well as highly complex cases, which makes the level of care provided extraordinary and unique.

Richard L. Menschel

Hospital for Special Surgery

535 East 70th Street New York, NY 10021 212.606.1000 www.hss.edu