DIVISION OF RHEUMATOLOGY

2008-2009 ANNUAL REPORT

INSIGHTS AND INNOVATIONS

CONTENTS

Leadership Report 2

Systemic Lupus Erythematosus 6

Rheumatoid Arthritis, Spondyloarthropathy 10and Uveitis

Vasculitis and Scleroderma 13

Osteoarthritis 15

Metabolic Bone Disease and 17Orthopaedic Bone Health

Pediatric Rheumatology 18

Professional Staff 19

2008-2009 Notable Achievements 21

2008-2009 Selected Publications 24

On the cover:(Left to right) Robert F. Spiera, MD,Director, Vasculitis and SclerodermaProgram; Lionel B. Ivashkiv, MD,Associate Chief Scientific Officer,and Carl P. Blobel, MD, PhD, ProgramDirector, Arthritis and TissueDegeneration Program; and Lisa A.Mandl, MD, MPH, Co-Director of theCenter for Education and Researchon Therapeutics grant, exemplify theimportance of the Hospital’s integratedprogram of medicine and science.

On this page:Translating basic findings into newways of treating musculoskeletalconditions and autoimmune diseasesis at the heart of Hospital for SpecialSurgery’s mission. At HSS, scientistssuch as Lionel B. Ivashkiv, MD, (top)and clinicians such as Linda A. Russell,MD, work closely together, bringingclinical questions into the laboratoryand applying basic science discoveriesin a meaningful way to help patients.

DIVISION OF RHEUMATOLOGY1. Dr. Ora Singer 2. Dr. Diana A. Yens 3. Dr. Robert F. Spiera 4. Dr. Steven K. Magid 5. Dr. George Kalliolias6. Dr. Hendricks H. Whitman III 7. Dr. Richard Stern 8. Dr. Thomas J.A. Lehman 9. Dr. Doruk Erkan 10. Dr. Susan M. Goodman11. Dr. C. Ronald MacKenzie 12. Dr. Dalit Ashany 13. Dr. Lisa A. Mandl 14. Dr. Alexa B. Adams 15. Dr. Inez Rogatsky16. Dr. Juliet B. Aizer 17. Dr. Aruni Jayatilleke 18. Dr. Diana Goldenberg 19. Dr. Emma Jane MacDermott20. Dr. Danieli C. Andrade 21. Dr. L. Nandini Moorthy 22. Dr. Jessica R. Berman 23. Dr. Richard S. Bockman

Patient Care• Growth and expansion of the Hospital’s Center for

Musculoskeletal Perioperative Medicine and the

Hospitalist Program

• Opening of the Center for Inflammatory Arthritis and

Innovative Biologic Therapy and the Mary Kirkland Center

for Lupus Care

• Initiation of the Cardiovascular Disease Prevention Program

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INSIGHTS AND INNOVATIONS

DIVISION OF RHEUMATOLOGY

24. Dr. Sergio Schwartzman 25. Dr. Harry Bienenstock 26. Dr. Bento R. Mascarenhas 27. Dr. Lawrence J. Kagen28. Dr. Laura V. Barinstein 29. Dr. Beverly Johnson 30. Dr. Lindsy Forbess 31. Dr. Kun Chen 32. Dr. Sabeen Anwar33. Dr. Weijia Yuan 34. Dr. Edward J. Parrish 35. Dr. Stephen J. DiMartino 36. Dr. Charis F. Meng 37. Dr. Joseph A. Markenson38. Dr. Allan Gibofsky 39. Dr. Stephen A. Paget 40. Dr. Jane E. Salmon 41. Dr. Theodore R. Fields 42. Dr. Michael D. Lockshin43. Dr. Anne R. Bass 44. Dr. Carol A. Mancuso 45. Dr. Linda A. Russell 46. Dr. Alana Levine

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Clinical Advances• Evaluating the role of rituximab in the treatment of

ANCA-related vasculitides

• Determining the efficacy of Gleevec® in scleroderma

• New therapeutic targets in osteoarthritis

• New and effective treatment regimens for refractory

pediatric autoimmune disorders

Research• Uncovering the role of interferon alpha in SLE, rheumatoid

arthritis and scleroderma

• The promise of the PROMISSE study in defining risk

factors for pregnancy loss in patients with SLE and

antiphospholipid syndrome

• Vascular endothelial cell genetic analysis as an approach

to defining causes of premature atherosclerosis

OUR MISSION

The mission of the Division of Rheumatology, first and foremost, is to

enhance the quality of life for the thousands of patients who come to

Hospital for Special Surgery each year seeking our care. This is made

possible by a seamless integration of medicine, science, and education

that enables us to continually identify clinical challenges, carry out the

studies that will help us develop better methods of treatment, facilitate

the application of therapeutic advances to the patient care setting, and

engage new and seasoned physicians and researchers in unparalleled

fellowship training and continuing medical education opportunities.

Our unwavering commitment to this

mission will help ensure that adults

and children with musculoskeletal

and autoimmune disorders

receive the best possible care

here and everywhere.

Stephen A. Paget, MD Mary K. Crow, MD

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Dear Colleague:

We are proud to bring you the 2008-2009 Annual Report of the Division of Rheumatology at Hospital

for Special Surgery. As members of the professional staff of the largest musculoskeletal specialty

hospital in the world, our dedication is to nothing less than assuring a longer and better life for our

patients. To achieve that end, our clinicians and scientists are provided with significant opportunities

for advancing patient care, education, and research in the field.

Enhancing Care for Patients

Recently, we introduced two new programs—the Mary Kirkland Center for Lupus Care and the Center

for Inflammatory Arthritis and Innovative Biologic Therapy—to enhance our ability to provide

disease-focused care for specific populations. You will read more about these programs on the pages

that follow.

During the past year, physicians in the Hospital’s Division of Rheumatology served as the

musculoskeletal perioperative specialists for over 12,000 orthopaedic surgery patients. The Hospital’s

Center for Musculoskeletal Perioperative Medicine, directed by rheumatologist C. Ronald MacKenzie,

MD, and anesthesiologist Michael K. Urban, MD, PhD, assures the best outcomes for our orthopaedic

surgery patients – many of whom present with complex clinical issues.

Rheumatologist Steven K. Magid, MD, played a leadership role during the Hospital’s development and

implementation of a new quality review infrastructure, which set in place mechanisms to allow better

alignment of strategic goals, sharing of information, and the setting of benchmarks and metrics.

Theodore R. Fields, MD, Clinical Director of the Early Arthritis Initiative, serves as Co-Chairman of

the Hospital’s Web Committee and Director of the HSS Rheumatology Website, which has over 800

articles and a large number of videos, audio material, podcasts, and online CME programs. The

Rheumatology Website attracts 280,000 unique users a month. Dr. Fields also chairs the Hospital’s

CliniCIS Content Board responsible for reviewing changes and improvements to the Computerized

Prescriber Order Entry system, including computerized alerts to physicians to improve practice and

built-in safety elements such as making it simple to order blood levels when certain antibiotics are

prescribed.

LEADERSHIP REPORT

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Reinforcing Our Research EffortsFrom research innovations that arise in our basic science laboratories to therapeutic

insights that develop from collaborations at the translational and clinical levels, the

Division of Rheumatology maintains a steadfast commitment to finding solutions

in the laboratories and at the bedside for complex clinical problems. In fact, the

translation of basic and clinical research findings into applications for medical care

is a hallmark of Special Surgery’s “bedside-to bench-to-bedside” approach.

We are pleased to report that in an era in which the National Institutes of Health had

less available funds to provide for research, HSS increased its federal grant portfolio

by 14.6 percent over 2007, with awards totaling $22.4 million. Total active awards

for 2008 totaled $32.7 million, an increase of 14.2 percent or $4.1 million

over the previous year.

With this level of support, our clinicians and scientists are able to continue their

groundbreaking research, which includes studies in:

Systemic Lupus Erythematosus• the innate immune response and the genetic, environmental, and immune

mechanisms that contribute to activation of the type 1 interferon pathway

• biomarkers to predict disease flare

• predictors of pregnancy outcomes

• drug trials for difficult-to-treat antiphospholipid syndrome patients and patients

who are antiphospholipid antibody positive

Rheumatoid Arthritis• role of cytokines in inflammation

• relationship of tumor necrosis factor and type 1 interferon to immune

system function

• mechanisms of joint destruction

Osteoarthritis• collagen remodeling in osteoarthritis

• protein targets in osteoarthritis disease onset and progression

• mechanisms of induction of inflammation

• preserving cartilage following injury

Vasculitis and Scleroderma• phase IIa trial of imatinib (Gleevec®) in the treatment of diffuse systemic sclerosis

• high-dose immunosuppressive therapy in autologous stem cell transplant as a

treatment for severe systemic sclerosis

• type 1 interferon action in scleroderma

• rituximab for ANCA-associated vasculitis

(Top) C. Ronald MacKenzie, MD, andhis colleagues are responsible for thepre- and post-operative consultationand care of surgical patients. (Middle)Steven K. Magid, MD, founded theClinical Informatics Committee of theMedical Board to promote clinicianinvolvement in the Hospital’s clinicalinformatics initiatives. (Bottom)Theodore R. Fields, MD, plays a keyrole in the Hospital’s ComputerizedPrescriber Order Entry system.

Metabolic Bone Disease and Orthopaedic Bone Health• methods to enhance bone formation and regeneration in arthritis patients

• mechanisms of tissue destruction in periodontitis

• use of anticatabolic drugs to treat new fractures

Pediatric Rheumatology• systematic use of cyclophosphamide and rituximab in a new protocol for children

with severe SLE

• evaluation of the use of a similar regimen of cyclophosphamide and rituximab for

children with scleroderma

• the role of cytokine gene polymorphisms in conferring risk and protection in

juvenile dermatomyositis

In 2008, Lionel B. Ivashkiv, MD, Senior Scientist and Director of Basic Research,

was appointed Associate Chief Scientific Officer. In this newly created position,

Dr. Ivashkiv, who is the David H. Koch Chair in Arthritis and Tissue Degeneration,

is charged with developing a long-term strategic plan for basic science research

programs; fostering collaborative research among the basic science programs; and

enhancing translational research. Dr. Ivashkiv has an outstanding record of NIH

funding and has made major contributions to the understanding of inflammatory

mechanisms in autoimmune and musculoskeletal disorders.

For the past two years, the Hospital has been moving forward with the integration of

its basic, translational, and clinical research efforts to allow us to maintain dynamic

cutting-edge programs and sustain our level of scientific excellence into the future.

By closely aligning research and clinical priorities, we can expedite the application of

new therapies to the treatment of patients with musculoskeletal and autoimmune dis-

eases. Translational research teams, made up of clinicians and basic scientists, have

targeted a number of areas to address, with one of our largest translational research

efforts to date focused on systemic lupus erythematosus and complications of the

disease related to pregnancy, neurocognitive function, and cardiovascular system.

In addition, the Hospital is participating in a new Clinical and Translational Science

Center led by Weill Cornell Medical College. Peggy Crow, MD, Director of Special

Surgery’s Autoimmunity and Inflammation Program, is serving as one of two

Coordinating Program Directors for the Center, which is funded by a $49 million

National Institutes of Health grant.

As the largest provider of musculoskeletal care—with more than 250,000 patient

visits for musculoskeletal disorders and autoimmune diseases annually—we are in

a pivotal position to be able to document factors that affect patient outcomes. The

Hospital currently has more than 30 patient registries ranging from those for very

specific conditions, such as basal joint arthritis, to more broad-based databases,

such as the Autoimmune Disease Registry and Repository.

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By closely aligning

research and clinical

priorities, we can

expedite the application

of new therapies to the

treatment of patients

with musculoskeletal

and autoimmune

diseases.

Total NIHRheumatology

Awards

33

Other NIHAwards

40

Hospital for Special SurgeryResearch Institute

2008 ActiveNational Institutes of Health Awards

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(Top to bottom) Anne R. Bass, MD,Juliet B. Aizer, MD, MPH, and JessicaR. Berman, MD, play key roles at thenational level in the development andimplementation of education andtraining programs for rheumatologyfellows. Dr. Berman recently receivedan ACR REF Clinician ScholarEducator Award for her innovativeresident educational programs.

Our Education MissionEach and every day we carry out our mission to provide exemplary education

programs for Weill Cornell medical students and residents, rheumatology fellows, and

seasoned physicians who come to HSS to train. In 2008-2009, we had 11 fellows in

rheumatic disease and another four fellows in pediatric rheumatology. Our three-year

Rheumatology Fellowship Program draws on the clinical and research resources

of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, Memorial Sloan-

Kettering Cancer Center, and The Rockefeller University. Fellows gain clinical

experience at outpatient clinics focused on adult and pediatric rheumatology and a va-

riety of orthopaedic subspecialties. The program emphasizes research into the

biological mechanisms of autoimmune, inflammatory, and musculoskeletal disease,

and issues pertinent to clinical epidemiology and health services delivery.

On a national level, Anne R. Bass, MD, Program Director of the Division’s Fellowship

Training Program, serves as Chairman of the American College of Rheumatology

Training Resources Subcommittee of the Committee on Workforce and Training. Her

responsibilities include chairing the panel that rewrites the rheumatology in-training

exam and managing the Rheumatology Fellowship Match Program. Juliet B. Aizer, MD,

MPH, and Jessica R. Berman, MD, Director of Resident Education at HSS, participated

in the development of rheumatology education as representatives to the American

College of Rheumatology Committee on Education.

Dr. Berman continues to coordinate the yearly ROSCE (Rheumatology Objective

Structured Clinical Examination), a citywide assessment tool for evaluating Rheuma-

tology fellows in areas such as professionalism and patient care skills. The last five

years of course data demonstrating ROSCE’s validity and usefulness as a unique

rating tool will soon be published in Arthritis Care and Research.

Leading the WayWhether members of the Division of Rheumatology are participating in national or

global conferences, collaborating with colleagues within the Hospital and around the

country, or serving in leadership positions with professional societies or internal

Hospital committees, they do so with a commitment to ultimately providing the highest

quality of care for patients with musculoskeletal conditions and autoimmune

disorders. We hope you enjoy reading about their individual and collaborative

accomplishments in the report that follows.

Stephen A. Paget, MD, FACP, FACR Mary (Peggy) K. Crow, MD

Physician-in-Chief and Director, Rheumatology Research

Chairman, Division of Rheumatology

Systemic lupus erythematosus (SLE) is a major focus of the Division of

Rheumatology’s clinicians and scientists, who seek to develop new approaches

for managing SLE and its complications. Currently, our research efforts include

investigations of mechanisms of type 1 interferon pathway activation in SLE;

biomarkers involved in the prediction of disease flare; antiphospholipid syndrome and

antiphospholipid antibody positive patients; and predictors of pregnancy outcome.

Type 1 Interferon PathwayOur scientists have particular interest in the innate immune response and the genetic,

environmental, and immune mechanisms that contribute to activation of the type 1

interferon pathway (including production of interferon-alpha). Interferon-alpha is a

cytokine that is typically produced in the setting of viral infection. In systemic

autoimmune diseases, such as lupus, we observe increased production of interferon-

alpha that is associated with increased disease activity and increased production

of autoantibodies that target RNA-associated proteins. In studies performed in

collaboration with Timothy B. Niewold, MD, a former HSS rheumatology fellow,

we have identified that certain lupus-associated genetic variants confer increased

production or response to interferon-alpha. Several of the proteins encoded by those

genetic variants map to the Toll-like receptor pathway, implicating that molecular

pathway in production of interferon.

Additional studies in the Hospital’s laboratory are investigating the characteristics

of the stimuli for Toll-like receptor activation. Plasma autoantibodies and their

associated DNA or RNA from patients with lupus have been characterized for their

capacity to activate the interferon pathway. Our researchers have found that auto-

antibodies specific for RNA-associated proteins are more active than anti-DNA anti-

bodies in stimulating this pathway. This is consistent with our earlier studies show-

ing an association between those autoantibodies and interferon pathway activation.

We are also investigating the nature of the RNAs that induce interferon.

The compelling support for a central role for interferon-alpha in lupus pathogenesis

has led to a new focus on the role of innate immune system activation in the genera-

tion of pathogenic mediators. These insights have been extended to translational

studies of patients with well-characterized disease activity and clinical manifesta-

tions in order to identify informative molecular biomarkers. Our researchers are

studying a cohort of lupus patients in order to determine the relationship of fluctua-

tions in interferon pathway activation to flares in disease activity. This study has

compiled one of the most complete and well-documented datasets, including several

disease activity measures and biologic samples that have been monitored over

three years. Chemokines are among the interferon-inducible genes, and new data

support an association between the expression of chemokines and both lupus

disease activity and organ damage. Longitudinal studies that relate molecular

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SYSTEMIC LUPUS ERYTHEMATOSUS

PROFESSIONAL STAFF

Mary K. Crow, MD

Doruk Erkan, MD, MPH

Diane A. Goldenberg, MD, MPH

Roberta Horton, LCSW, ACSW

Suzy Kim, LCSW

Kyriakos A. Kirou, MD, FACR

Juliette Kleinman, LCSW, ACSW

Elizabeth Kozora, PhD

Michael D. Lockshin, MD

Lillian Mendez

Jillian Rose, LMSW

Jane E. Salmon, MD

Lisa R. Sammaritano, MD

Erica Sandoval

My-Lan Tran, LCSW

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biomarkers to disease activity will be needed to validate these promising data and

establish a sensitive measure of change for interventional studies and patient care.

This work is leading to new understanding of lupus pathogenesis and development

of biomarkers that might eventually be used to predict disease flares and is con-

tributing to the rationale for drug development programs that involve monoclonal

antibodies specific for interferon-alpha.

Antiphospholipid Syndrome and Antiphospholipid Antibody Positive PatientsResearchers at Hospital for Special Surgery are involved in multiple clinical trials

ranging from mechanistic studies to drug trials for difficult-to-treat antiphospholipid

syndrome (APS) patients and patients who are antiphospholipid antibody positive

(aPL positive). They continue to pursue the identification of factors that increase the

risk of blood clots, which occur when an antibody attaches to an endothelial cell on

the vessel wall, triggering reactions that result in clotting. Currently, patients prone to

blood clots are given an anticoagulant to prevent this from occurring. Although blood

thinners reduce the risk of the antibody attaching to the arterial or venous wall, they

do not change the nature of the potentially harmful antibodies or control or prevent

renal or cardiac complications.

One clinical trial currently underway through the Hospital’s Barbara Volcker Center

for Women and Rheumatic Diseases and in conjunction with the University of Texas

Medical Branch Rheumatology Clinic, seeks to address the blood clot and cardiovas-

cular disease challenges of patients with APS and those who are aPL positive. The

study is investigating whether a statin drug—traditionally used to lower choles-

terol—is beneficial and safe in reducing the risk of cardiovascular disease and blood

clots in these patients. The study has also been designed to allow researchers to

observe the effects that the medication has on the antibodies.

MARY KIRKLAND CENTERFOR LUPUS RESEARCH

Stephen A. Paget, MDMary K. Crow, MDMichael D. Lockshin, MDJane E. Salmon, MDCo-Directors

In 2001, with support fromKatherine and Arnold Sniderof Rheuminations, Inc., Hospitalfor Special Surgery inauguratedthe Mary Kirkland Center forLupus Research to further newunderstanding of the molecularand cellular basis of systemiclupus erythematosus, contributeto the development of new lupustherapies, and improve the livesof patients with lupus. Researchprojects address disease sus-ceptibility, alterations in immunefunction, mechanisms of targetorgan damage, epidemiology,clinical features, and newtherapies for lupus.

Michael D. Lockshin, MD (left), Director, and Doruk Erkan, MD, Associate Director, Barbara VolckerCenter for Women and Rheumatic Diseases, are exploring new ways to help patients suffering fromantiphospholipid syndrome.

The scientific achievements ofJane E. Salmon, MD, particularlyin the area of lupus pregnancy,have earned her national andinternational accolades.

In aPL positive patients, clinical manifestations may include low platelet count,

anemia, heart valve disease, skin ulcers, kidney small blood vessel clots, and memory

problems. Current treatments available for this syndrome have not been satisfactory.

Another clinical trial taking place at HSS is a pilot study evaluating whether ritux-

imab, approved for treatment of non-Hodgkin’s B-cell lymphoma and for certain

patients with rheumatoid arthritis, will reduce the signs and symptoms of aPL-

related clinical problems.

Through these clinical trials, the Hospital’s rheumatologists hope to define new

principles of treatment that will improve the lives of patients with APS or who are

aPL positive. At the same time, the Division of Rheumatology has launched a cardio-

vascular disease prevention counseling program for patients with lupus and/or who

are aPL positive. Studies have demonstrated that patients with lupus have higher

rates of cardiovascular risk factors and cardiovascular events compared to healthy

individuals. Furthermore, patients who are persistently positive for aPL are at in-

creased risk for blood clots. The comprehensive program evaluates patients for

traditional cardiac risk factors such as blood pressure, blood glucose, cholesterol

levels, body mass index, diet and exercise habits, smoking status, as well as for aPL

profile, medication usage, and non-traditional and lupus-specific risk factors.

The PROMISSE Study: Predictors of pRegnancy Outcome: bioMarkers Inantiphospholipid antibody Syndrome and Systemic lupus ErythematosusPatients with SLE and/or antiphospholipid antibodies are at increased risk for

miscarriage, preeclampsia, and fetal growth restriction—major causes of maternal,

fetal, and neonatal morbidity and mortality. The etiology of these conditions remain

unknown and therapy is limited.

In 2008, the National Institutes of Health extended the PROMISSE study, a multi-

center effort coordinated by Hospital for Special Surgery, for an additional five years,

beginning with $1.4 million for the first year of renewal. This competitive renewal

and extension allows the Hospital’s investigators and co-investigators from 11

academic centers across the country to increase patient enrollment to 700—550

patients with aPL antibodies and/or SLE and 150 healthy controls. In addition, they

will be able to continue to identify biomarkers that predict poor pregnancy outcome

in these patients, elucidate mechanisms of disease, and choose novel therapeutic

targets to prevent such outcomes. Further, they will expand the study to examine a

broader range of genes and molecular pathways that can affect pregnancy in patients

with lupus, and potentially cause miscarriage and preeclampsia in healthy women.

Since the study’s launch in September 2003, the Hospital has been extremely successful

in the recruitment of participants for PROMISSE, enrolling 500 patients in this study

as of June 1, 2009.

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SYSTEMIC LUPUS ERYTHEMATOSUS

PROMISSE STUDYPatient Registry Enrollment

2003 TO 2009(as of June 2009)

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Although the primary hypotheses will not be tested until enrollment is near complete,

our researchers have harnessed the PROMISSE cohort to accomplish the following:

• determined which assay(s) of aPL antibodies are associated with the highest risk of

complications to identify predictors of pregnancy outcomes

• exploited the well-defined phenotype and the study design of PROMISSE to analyze

the severity, frequency, and timing of flares and the fetal outcomes in 198 PROMISSE

SLE patients—a group with stable or mildly active disease at conception

• initiated studies to examine the prevalence of variants in genes that regulate

complement activation

As the study continues, PROMISSE will determine in a prospective cohort of

pregnant patients:

• whether elevations of split products, generated by activation of the alternative

or classical complement pathways, predict poor fetal outcome in patients with

antiphospholipid antibodies (aPL) and/or SLE

• whether the balance of circulating angiogenic and antiangiogenic factors predict

poor fetal and/or maternal outcome in patients with aPL antibodies and/or SLE.

In addition, basic research is taking place to determine the mediators and mechanisms

of aPL antibody-induced pregnancy loss and preeclampsia in animal models. Current

work is directed at defining the initiators and effectors of fetal and placental injury to

refine targets for treatment within and beyond complement pathways. Pathways iden-

tified in the animal studies guide our studies of biomarkers and genetic risk factors in

the PROMISSE study. Elucidating the role of specific complement components and

downstream effectors and the role of complement activation within the overall inflam-

matory cascade will provide a basis for developing new therapies, a rationale for

choosing among them, and the potential to improve patient outcomes.

Atherosclerosis in SLE PatientsAccelerated atherosclerosis has emerged as a significant threat to the health of

patients with SLE. Endothelial dysfunction represents the earliest stage of the

atherosclerotic process. In collaboration with the Division of Cardiology at Columbia

University College of Physicians and Surgeons, we are examining the relationship

between endothelial biomarkers of vascular inflammation and atherosclerotic

burden in patients with SLE. Our goal is to characterize the gene expression profiles

relevant to atherosclerosis and to the interferon pathway in endothelial cells and

elucidate the pathways that promote atherosclerosis in SLE using a novel minimally-

invasive approach to sample vein endothelial cells. The ultimate goal is to identify

targets for treatment and means to monitor therapies in these at-risk patients.

MARY KIRKLAND CENTERFOR LUPUS CARE

Doruk Erkan, MD, MPH, andKyriakos A. Kirou, MDClinical Co-Directors

Jane E. Salmon, MDDirector, Translational Research

Pretima Persad, MPHManager

In July 2009, Hospital for SpecialSurgery established the MaryKirkland Center for Lupus Carewith the ultimate goal of providinga better quality of life for patientswith lupus and/or antiphospholipidsyndrome.

The Mary Kirkland Center forLupus Care provides:

• comprehensive, multidisciplinarypatient assessments

• social work evaluation

• patient education programs

• support programs, including: LupusLine®

Charla de Lupus/Lupus Chat®LANtern® Lupus Asian Network SLE WorkshopVOICES 60+

• resource referral

• cardiovascular diseaseprevention counseling

• access to clinical trials

• coordination of all lupus clinicalresearch projects and integrationwith lupus basic and translationalscientists

PROFESSIONAL STAFF

Adena Batterman, MSW, LCSW

Theodore R. Fields, MD, FACP

Allan Gibofsky, MD, JD, FACP,FCLM

Steven R. Goldring, MD

Susan M. Goodman, MD

Lionel B. Ivashkiv, MD

Dayna Kurtz, LMSW

Joseph A. Markenson, MD

Dana E. Orange, MD

Stephen A. Paget, MD, FACP,FACR

Sergio Schwartzman, MD

Millicent Stone, MD

Lisa C. Vasanth, MD, MS

Scientists and clinicians in the Division of Rheumatology continue to enhance our

understanding of rheumatoid arthritis (RA) and spondyloarthropathy through basic

research studies and the establishment of comprehensive clinical centers such as the

new Center for Inflammatory Arthritis and Innovative Biologic Therapy. The estab-

lishment of the new Center not only permits optimal specialized care for patients with

inflammatory arthritis but enables and facilitates translational research focusing on

important issues that include, for example, the role of cytokines in mediating

inflammation and the development and evaluation of novel therapeutic targets to

prevent joint destruction.

Understanding Cytokine’s Role in InflammationIn the laboratory of the Arthritis and Tissue Degeneration Program, research centers

on how modulating cytokine signaling impacts cell function and gene expression,

and the relationship of these changes to the severity of inflammation and related

tissue damage. The Hospital’s researchers have shown, for example, that the func-

tion of the cytokine interleukin-10 (IL-10), which normally suppresses inflammation,

is turned off in rheumatoid arthritis, while in systemic lupus erythematosus, the

effective functioning of IL-10 is reprogrammed and contributes to inflammation.

Studies are now underway to further characterize mechanisms that regulate cellular

signaling by the Jak-STAT pathway, which is used universally by many cytokines

and found in a diversity of cell types. Researchers are studying mechanisms that

mediate crosstalk between this and other major signaling pathways, and determining

whether modulation or “reprogramming” of cytokine signaling during inflammation

affects the balance of cytokine action. In their analysis of cytokine regulation of

tissue destruction and remodeling, they have identified mechanisms by which interfer-

ons, cytokines at times used to treat autoimmune diseases, suppress tissue destruction

and protect against bone loss that predisposes to osteoporosis. This work has resulted

in a number of publications in which potential therapeutic targets and mechanisms

for treatment of inflammatory and rheumatic diseases have been reported.

The extent of inflammation and rate of associated bone destruction in RA are

determined by the balance between inflammatory factors and the mechanisms that

oppose inflammation and bone resorption, and promote healing. IL-10 suppresses

osteoclast-mediated bone resorption, which results in bone destruction, by inhibiting

signaling by RANK, a key receptor required for osteoclast formation and activity.

A study is underway to identify the mechanisms by which IL-10 inhibits RANK

signaling with the goal of translating this information into approaches for attenuat-

ing inflammation-induced osteoclast-mediated bone destruction.

Exploring the Function of Type 1 InterferonThe Hospital’s researchers have discovered that increased levels of type 1 interferon

in plasma are associated with beneficial therapeutic responses to tumor necrosis factor

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RHEUMATOID ARTHRITIS, SPONDYLOARTHROPATHY AND UVEITIS

Steven R. Goldring, MD, Chief Scientific Officer (left) and Lionel B. Ivashkiv, MD, Associate ChiefScientific Officer, pursue pacesetting research in rheumatoid arthritis. Dr. Goldring was recently appointedChairman of the Research Committee of the National Arthritis Foundation and is the only New York-based rheumatologist selected to participate in the American College of Rheumatology Research andEducation Foundation program entitled, “Within Our Reach: Finding a Cure for Rheumatoid Arthritis.”Dr. Ivashkiv was the lead investigator on a study published in the November 14, 2008 issue of Immunity,which identified a potential new therapeutic target that could be used to treat inflammatory disorders, suchas rheumatoid arthritis. He recently was awarded his fourth National Institutes of Health RO1 grant.

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(TNF) inhibitor therapy in patients with rheumatoid arthritis. They suspect that in

contrast to interferon-alpha, which is widely disseminated and impacts many aspects

of immune system function in patients with SLE, in patients with RA, interferon-beta

might be a protective factor that is produced predominantly in the inflamed joint and

augments the anti-inflammatory effects of TNF inhibitors. They are now looking at

the role of interferon-beta as a predictor of response to TNF antagonist therapy in

RA. They also are evaluating the effectiveness of switching the specific anti-TNF

agent in a cohort of RA patients, and assessing the persistence of response and

remission associated with specific TNF antagonists.

Identifying Mechanisms of Joint DestructionThe mechanism of joint destruction in rheumatoid arthritis, specifically related to

osteoclast activity, has been a long-standing interest of Steven R. Goldring, MD, the

Hospital’s Chief Scientific Officer. In patients with rheumatoid arthritis, osteoclasts –

which usually clear away damaged bone and promote new bone growth and repair –

begin to destroy the healthy bone around joints. Little is known about the causes of

this role reversal, and treatment options are currently limited. In an effort to discover

novel therapeutic targets to prevent joint destruction, Dr. Goldring seeks to determine

the genes and signals that activate the osteoclasts to destroy bone. His work in this

area led to his selection by the American College of Rheumatology Research and

Education Foundation as one of only 15 scientists in the United States to be awarded

an Innovative Basic Research grant in recognition of novel research that is expected

to change the future treatment of rheumatoid arthritis. Dr. Goldring’s findings could

help to prevent irreversible joint damage and disability in patients with RA.

The Hospital’s

researchers have

discovered that

increased levels of

type 1 interferon in

plasma are associated

with therapeutic

responses to tumor

necrosis factor (TNF)

inhibitor therapy

in some patients with

rheumatoid arthritis.

(Top) Sergio Schwartzman, MD,Director, and Allan Gibofsky, MD,JD, Co-Director, are developing theclinical, scientific, and educationalgoals of the Center for InflammatoryArthritis and Innovative BiologicTherapy.

12

RHEUMATOID ARTHRITIS, SPONDYLOARTHROPATHY AND UVEITIS (CONT.)

THE CENTER FOR INFLAMMATORY ARTHRITISAND INNOVATIVE BIOLOGIC THERAPY

In 2008, the Hospital established the Center for Inflammatory Arthritis and InnovativeBiologic Therapy (IAC) based on “best evidence medicine” with the following intersectingtenets:

• to provide comprehensive care to patients with RA and spondyloarthropathies

• to educate medical students from the Weill Cornell Medical College, residents fromNewYork-Presbyterian Hospital, and fellows and attendings from HSS

• to facilitate translational research by enhancing communication between basic scienceresearchers and clinicians and formulate the foundations for clinical research at HSS

• to promote basic and clinical collaborations with the pharmaceutical industry andparticipate in the development of novel therapeutics for patients with inflammatory arthritis

As part of its commitment to providing optimal care to patients, the IAC conducts a weeklyclinic, followed by a conference involving rheumatology attendings, a radiology attending,medical students, residents, fellows, and social workers in an interdisciplinary discussionof patients with diverse clinical problems so as to highlight evidence-based therapeuticdecisions and assessment of outcomes. The Center has developed and implemented acomprehensive computerized registry and a database of patients with rheumatoid arthritis.Registries in other inflammatory conditions, including ankylosing spondylitis and psoriaticarthritis, are being developed. In addition, the Center serves as a site of the nationalConsortium of Rheumatology Researchers of North America (CORRONA).

The Early Arthritis Initiative, a component of the IAC, will educate both physicians andpatients on the benefits of early diagnosis and treatment of inflammatory arthritis, withan emphasis on the concept of the “window of opportunity;” enroll patients with earlyinflammatory arthritis in the IAC database; and participate in basic and clinical studiesrelated to early inflammatory arthritis.

Three clinical trials that were incorporated into the IAC are nearing completion, and two newstudies are soon to be launched. Proposals for several investigator initiated trials have beensubmitted on several topics including the use of a new anti-biological agent, certolizumab.In addition, several national and international database collaborations are being explored. Aneffort to promote a closer interaction between clinical and basic science research at HSShas been initiated. This translational approach has encompassed several activities, includinga project on the characterization of cytokines and dendritic cells in patients with psoriaticarthritis. Two new Fellowship research studies have been proposed that require the facilitiesof the IAC.

As the Center for Inflammatory Arthritis and Innovative Biologic Therapy continues todevelop, the primary objectives will be to continue to build the respective registries soas to begin generating hypotheses, research studies, and publications that cross the basicscience and clinical platforms.

Sergio Schwartzman, MDDirector

Allan Gibofsky, MD, JD, FACP, FCLMCo-Director

Dana E. Orange, MDConsultant, Translational Medicine

Millicent Stone, MDConsultant, Ankylosing Spondylitis

Theodore R. Fields, MDConsultant, Early Arthritis Initiative

Carla WilliamsCoordinator, Inflammatory Arthritis Center(IAC)

Susan KimSocial Work Coordinator

13

SclerodermaScleroderma has become a major focus of clinical and translational investigations at

Hospital for Special Surgery. This was facilitated by the establishment of the Rudolf

Rupert Scleroderma Research Center in 2005. Directed by Robert F. Spiera, MD, the

Center created an infrastructure for clinical, translational, and basic research in

scleroderma, as well as for community outreach and patient and physician education.

A number of components have matured in the past few years. The scleroderma

registry is a prospective, observational, longitudinal database that collects clinical

information and biological materials to further basic scientific research and clinical

studies of patients with scleroderma. Collaborative work with other scleroderma

centers of excellence is ongoing, allowing this resource to be of value to the broader

scleroderma research community.

The first and largest single center prospective phase IIa trial of imatinib (Gleevec®),

a tyrosine kinase inhibitor, in the treatment of diffuse systemic sclerosis is currently

nearing completion under the direction of Dr. Spiera, and in collaboration with

Jessica Gordon, MD, a senior rheumatology fellow. An interim analysis suggested

acceptable safety and tolerability, but even more exciting has been the strong

suggestion of efficacy in terms of improvements in skin thickness, and even pre-

liminarily a suggestion of improvement in indices of lung function. These findings

were presented at the American College of Rheumatology Annual Scientific Meeting

in 2008, and will be further updated at the 2009 meetings. Studies of skin biopsies

from treated patients confirm the clinically measured improvement in skin thickness.

Basic laboratory investigations using skin, serum, and peripheral blood cells from

treated patients are ongoing, offering insights into how imatinib (Gleevec®) is work-

ing in these patients. An extension phase of the study will make up to two years of

further treatment available to patients who have completed the one-year trial. In

recognition of this work and her outstanding achievements in clinical and transla-

tional investigation under the mentorship of Dr. Spiera, Dr. Gordon was awarded a

2009 American College of Rheumatology Distinguished Fellow Award.

An industry-sponsored trial of dasatinib, a broader tyrosine kinase inhibitor, is now

underway at the Scleroderma Research Center, examining the safety and efficacy

of that agent in treating interstitial lung disease in patients with diffuse systemic

sclerosis. The Hospital also continues as a site for the National Institutes of Health-

funded Scleroderma: Cyclophosphamide or Transplantation Trial (SCOT) to evaluate

the potential benefit of high-dose immunosuppressive therapy and autologous stem

cell transplant as a treatment for severe systemic sclerosis.

The scleroderma registry and Gleevec® trials have served as a framework for some

exciting translational work in scleroderma. Several investigations are ongoing in the

laboratory. These include a search for biomarkers in scleroderma by using gene

VASCULITIS AND SCLERODERMA

PROFESSIONAL STAFF

Robert F. Spiera, MDDirector

Mary K. Crow, MD

Jessica Gordon, MD

Kyriakos A. Kirou, MD, FACR

Robert F. Spiera, MD, Director ofthe Vasculitis and SclerodermaProgram, is a pioneer in the field ofscleroderma research and has madeimportant inroads in the treatmentof this challenging disease.

expression analysis with microarray, studies of activation of the MAP kinase signal-

ing cascade in scleroderma, and investigations into the role of type 1 interferon acti-

vation in scleroderma. Studies of patients with scleroderma are showing activation

of the interferon pathway in those patients who have autoantibodies targeting RNA

or RNA-associated proteins, a common feature with our studies in patients with SLE.

Additionally, HSS scientists are investigating the mechanism of action of Gleevec®

in scleroderma, looking specifically at gene expression correlates of clinical response.

Researchers are also studying the contribution of mediators of angiogenesis in

scleroderma patients and have identified a candidate biomarker of pulmonary

dysfunction in those patients.

A grant by the Scleroderma Foundation Tristate Chapter is supporting a Sclero-

derma Program Coordinator who will foster the further development of clinical,

educational, and community outreach efforts in scleroderma at Hospital for Special

Surgery. In fall 2008, the Hospital hosted the Scleroderma Foundation Tristate

Chapter Research Symposium; this past spring, patient education forums were held.

A scleroderma support group meets regularly on site.

VasculitisIn the area of vasculitis, the ongoing RAVE (Rituximab for ANCA-associated

Vasculitis) study is investigating the effect of rituximab on remission induction in

patients with severe ANCA-associated vasculitis, comparing the safety and efficacy

of rituximab to conventional therapy with cyclophosphamide. The study has

completed enrollment, and analysis of the primary endpoint will be forthcoming

shortly. This large multicenter, prospective, randomized, and controlled clinical

trial—sponsored by the National Institute of Allergy and Infectious Disease and the

Immune Tolerance Network—may be pivotal in defining the state-of-the-art for

treatment of severe ANCA-associated vasculitis.

A multicenter international randomized trial exploring the role of plasmapheresis

in patients with severe ANCA-associated vasculitis is soon to be initiated. A collabo-

rative effort by the European Vasculitis Study Group and the U.S.-based Vasculitis

Clinical Research Consortium, this will be the largest prospective trial in vasculitis.

In 2008, Dr. Spiera chaired the Fourth International Conference on Giant Cell

Arteritis and Polymyalgia Rheumatica, which was hosted by Hospital for Special

Surgery and brought together internationally renowned thought leaders and experts

from 15 countries. Participants discussed both basic science and clinical topics essen-

tial to the practitioner caring for patients with these complex disorders and shared

their current understanding in the study and treatment of large vessel vasculitis.

14

Kyriakos A. Kirou, MD, is pursuingimportant basic science and clinicalstudies in scleroderma.

VASCULITIS AND SCLERODERMA

The scleroderma registry

and Gleevec® trials have

served as a framework

for some exciting

translational work in

scleroderma.

15

At Hospital for Special Surgery, a team of rheumatologists, scientists, orthopaedic

surgeons, and bioengineers are focused on the challenge of preventing the premature

development of osteoarthritis and examining the role of inflammation, joint mechan-

ics, and genetic influences, as well as the benefits of approaches for enhancing repair

of joint tissues after joint injury. Their efforts have been strengthened with the recent

creation of the Osteoarthritis (OA) Initiative—an integrated basic, translational, and

clinical research program that focuses on identifying risk factors for OA, prevention

or reduction of inflammation at the onset of the disease, new medical interventions,

and surgical solutions for treatment of OA.

Basic Research in OAAt the basic research level, the Laboratory of Cartilage Biology, directed by Mary B.

Goldring, PhD, is investigating mechanisms by which GADD45ß, a stress response

signaling molecule involved in cartilage development, and ESE1 (ELF3), an inflam-

mation-induced transcription factor, regulate collagen remodeling during osteoarthri-

tis. Studies using human surgical specimens and mouse models of OA, including

unbiased gene, protein, and microRNA profiling, may elucidate how these factors

disrupt cartilage homeostasis and lead to the development of targeted therapies that

block cartilage damage and promote effective repair. Dr. Goldring serves as the princi-

pal investigator for several National Institutes of Health research projects, including

a consortium for an R01 grant on a mechanistic study of osteoarthritis; an R01 grant

focused on the role of ESE in the development and progression of OA; and a study to

identify the protein involved in osteoarthritis disease onset and progression.

The Hospital’s researchers are also interested in defining the mechanisms of induc-

tion of inflammation in osteoarthritis. While it has long been believed that OA is

primarily due to degeneration of cartilage, more recent work has demonstrated

inflammatory infiltrates in the synovial membrane of OA patients. Our researchers

are identifying the gene products present in synovial membranes of patients with

early OA in order to understand the determinants of inflammation and progression

to end-stage disease with the goal of developing new therapeutic approaches.

Preserving Cartilage in the KneeThe arthritic process typically starts with damage to the cartilage surface, which can

appear as a small hole or defect. After an initial injury has caused damage to a

specific area of the cartilage, there are few options that can repair the damage, which

ultimately will lead to the development of osteoarthritis. A multicenter trial led by

orthopaedic surgeon Riley J. Williams III, MD, Director of the Hospital’s Institute for

Cartilage Repair, is focused on investigating a new minimally invasive alternative for

articular cartilage repair in the knee that may provide improved outcomes compared

to the current microfracture approach. A small piece of the patient’s healthy cartilage

is removed and broken into individual cells, which are grown in a laboratory and then

OSTEOARTHRITIS

Mary B. Goldring, PhD, Directorof the Hospital’s Laboratory ofCartilage Biology, is investigatingthe mechanisms involved in thedevelopment of osteoarthritis.She is a member of the Boardof Directors of the OsteoarthritisResearch Society.

PROFESSIONAL STAFF

Mary K. Crow, MD

Mary B. Goldring, PhD

Steven R. Goldring, MD

Howard J. Hillstrom, PhD

Lisa A. Mandl, MD, MPH

Hollis G. Potter, MD

Scott A. Rodeo, MD

Peter A. Torzilli, PhD

Riley J. Williams, III, MD

inserted into a protein matrix. Using the matrix as a scaffold, the cells begin to grow,

creating a piece of new cartilage that is then implanted through a small incision into

the damaged area, much like a living patch.

It is accepted that whether an anterior cruciate ligament (ACL) rupture is repaired or

not, osteoarthritis will develop in the knee five to 15 years after the injury. In the

Hospital’s Tissue Engineering, Regeneration, and Repair Program, Peter A. Torzilli,

PhD, Program Director, and his colleagues are studying the influence of trauma on

the remodeling and repair of articular cartilage. Their studies are designed to deter-

mine whether the development of OA after an ACL injury is related to the initial

damage to the articular cartilage or whether the progression to OA is secondary to

altered kinematics of walking and knee motion.

Examining OA Risk in ChildrenFunding from the Weill Cornell Medical College Clinical and Translational Science

Center is supporting a pilot study by Howard J. Hillstrom, PhD, Director of the Leon

Root, MD Motion Analysis Laboratory, on lower extremity alignment, gait, and joint

pathophysiology in overweight and normal weight children. Obesity presents numer-

ous problems to children including a greater risk of bone deformity and

osteoarthritis. There is a growing concern that overweight children may develop OA

at younger ages than previous generations.

Evaluating Joint Replacement SurgeryThe Center for Education and Research on Therapeutics (CERT), funded by the

Agency for Healthcare Research and Quality, is obtaining outcomes data on the

thousands of patients who undergo joint replacement surgery at HSS and supporting

clinical studies to determine the patient demographics, surgical techniques, and

prosthetic device characteristics associated with improved outcomes in total joint

replacement. The comprehensive CERT/HSS Total Joint Replacement Registry has

enrolled over 11,000 patients in two years. Data generated from the CERT has led to

a new group of safety initiative projects at HSS and the development of eight pilot

research studies designed to assess the determinants of favorable outcomes and the

economic impact of total joint surgeries.

Pain Relief for Basal Thumb OAA clinical study is underway to determine whether the drug hyaluronan can help

patients suffering with basal thumb OA. The goal is to determine if hyaluronan

provides better relief than both placebo or cortisone injections. A previous small,

open-label trial showed that hyaluronan provided a significant improvement in pain

among the 32 participants, leading the researchers to pursue a much larger study.

It has been shown that hyaluronan can work for three to six months in the knee;

researchers want to determine how long it will be effective in the thumb.

16

(Top) Lisa A. Mandl, MD, MPH, Co-Director of the Center for Educationand Research on Therapeutics(CERT) grant, is developing a majordatabase on patients undergoing jointreplacement surgery, which will pro-vide vital information for predictingthe factors that determine favorableoutcomes after joint replacmentand identify risk factors that areassociated with complications.(Bottom) Chris Chen, PhD, and PeterA. Torzilli, PhD, are uncoveringinformation that will help explain howan injury leads to the development ofosteoarthritis and joint destruction.

OSTEOARTHRITIS

17

A consortium of rheumatologists, endocrinologists, orthopaedic surgeons, and

scientists at Hospital for Special Surgery is focused on advancing the prevention

and treatment options for osteoporosis, Paget’s disease, and related bone disorders.

These clinicians and scientists pursue the common purpose of preserving the

quality of bone and enhancing bone healing.

Patients with fractures or individuals undergoing spinal and other types of surgery

often require treatments to enhance bone healing or replace or augment damaged

bone. Mesenchymal stem cells (MSCs), capable of differentiating into bone-forming

osteoblasts in response to the growth factor BMP-2, are a novel biological means to

enhance bone formation. Studies are underway to elucidate further understanding of

the mechanism by which MSCs are induced to become bone-forming cells. This will

potentially lead to the development of new methods to enhance bone formation and

regeneration. Our scientists have also identified stromal-derived factor-1 (SDF-1) as a

key molecule in bone healing, with the goal of improving healing after fractures.

Lionel B. Ivashkiv, MD, recently received his fourth NIH R01 award, which extends

the focus of his work to investigating the mechanisms of tissue destruction in

periodontitis. These studies focus on identifying mechanisms that can inhibit the

generation of osteoclasts, the cells that cause bone loss. This will provide insights

that can be exploited for therapeutic interventions to suppress the bone and tooth

destruction associated with periodontitis and other inflammatory conditions. Most

recently, HSS investigators, collaborating with researchers from other institutions,

have contributed to the discovery of a gene called interferon regulator factor-8

(IRF-8) that is involved in the development of periodontitis, rheumatoid arthritis,

and osteoporosis. The study, which was published online August 30, ahead of print

in the journal Nature Medicine, could lead to new treatments in the future.

In collaboration with centers across the country, HSS investigators are looking at

selected agents, including teraparitide—currently the only agent that is readily avail-

able in the United States—to build bone, enhance bone volume and bone synthesis,

and improve bone healing. In addition, the use of subcutaneous parathyroid hormone

in osteoporosis after failed treatment with bisphosphonates is being evaluated.

Under the direction of Joseph M. Lane, MD, investigators are testing therapeutic

agents that target molecules or pathways responsible for bone formation. They are

evaluating agents that block the chemicals responsible for interfering with these bone-

forming pathways—the next step towards developing enhanced bone production.

Through the Hospital’s Seymour Cohn Metabolic Bone Registry, patient data is

collected and analyzed to identify methods for preventing and repairing fragility

fractures. Based on the initial data, a pilot study is underway to identify possible

genes that may contribute to decreased bone quality that create susceptibility to

multiple fractures in some patients.

METABOLIC BONE DISEASE AND ORTHOPAEDIC BONE HEALTH

PROFESSIONAL STAFF

Juliet B. Aizer, MD, MPH

Richard S. Bockman, MD, PhD

Steven R. Goldring, MD

Lionel B. Ivashkiv, MD

Joseph M. Lane, MD

Martin Nydick, MD

Linda A. Russell, MD

(Top) Rheumatologist Linda A.Russell, MD, looks for osteoporosisin her patients, which can resultfrom medications used to treat RA.(Bottom) Joseph M. Lane, MD, Chiefof the Hospital's Metabolic BoneDisease Service, is leading a numberof basic and clinical research studiesaimed at improving treatment ofpatients with osteoporosis.

18

The Division of Pediatric Rheumatology at Hospital for Special Surgery is one of the

world’s preeminent pediatric rheumatology programs for both patient care and

physician education. The key aspect of the Division is its dedication to taking care of

children whose diseases are difficult to diagnose or treat. Many of the children cared

for have come to Hospital for Special Surgery because they have not been able

to get a proper diagnosis or appropriate care elsewhere. The Hospital’s pediatric

rheumatologists care for large numbers of children with difficult conditions where

“the answers are not in the textbook,” who did not respond to “standard” therapy.

The Division of Pediatric Rheumatology’s dedication to the care of children with

complex diseases for whom there is no “textbook answer” has made it a center of

excellence not just for New York City or the metropolitan area, but for children from

around the world.

The Division has pioneered new therapies that are now widely accepted therapies

for children with lupus, juvenile rheumatoid arthritis, uveitis, scleroderma, and

dermatomyositis. The faculty continues to work on a number of substantive new

projects related to documenting better therapies for children with rheumatic

diseases. The two most important are the systematic use of cyclophosphamide and

rituximab in a new protocol for children with severe SLE and lupus nephritis. The

combination of drugs provides dramatically improved outcomes for these patients

with a much lower overall cost in terms of frequency of hospitalization and total

amount of both corticosteroids and cyclophosphamide received. We have shown

that with less medicine we are getting far better results. 

The second major project is an evaluation of the use of a similar regimen of

cyclophosphamide and rituximab for children with scleroderma. This study is

going well, but because childhood scleroderma is rare, the answers are not yet in.

The Pediatric to Adult Rheumatology Transition Clinic, directed by Alexa B.

Adams, MD, is having continued success transitioning our pediatric patients to the

adult team as they mature to adulthood. The well-organized transition process puts

patients at ease with their new physicians, identifies a designated contact person,

and assures the appropriate transfer of information.

Hospital for Special Surgery has one of only 18 approved training programs for

fellows in pediatric rheumatology and continues to train fellows both from within

the United States and around the world. In addition, large numbers of physicians

from other countries visit our program for training periods of weeks to months. In

the last year, we have trained five physicians from Spain and one each from Israel

and Japan. Past graduates of our program are now directing pediatric rheumatology

programs in Singapore, Beijing, and Shanghai.

PEDIATRIC RHEUMATOLOGY

PROFESSIONAL STAFF

Thomas J.A. Lehman, MD,FAAP, FACR,Chief

Alexa B. Adams, MD

Theresa Lu, MD, PhD

Emma Jane MacDermott, MD,MRCPI

(Top) Thomas J.A. Lehman, MD,Chief of Pediatric Rheumatology,has garnered an internationalreputation for managing some ofthe most challenging cases in thefield. (Bottom) The Division ofPediatric Rheumatology hasexpanded with the addition ofEmma Jane MacDermott, MD,who completed her fellowship inpediatric rheumatology at Hospitalfor Special Surgery.

19

Kyriakos A. Kirou, MD, FACRCo-Director,Mary Kirkland Center for Lupus CareSLE, progressive systemic sclerosisresearch

Elizabeth Kozora, PhD SLE, antiphospholipid syndromecognitive function research

Thomas J.A. Lehman, MD, FAAP,FACRChief, Pediatric RheumatologyPediatrics, SLE, juvenile inflammatoryarthritis, psoriatic arthritis

Michael D. Lockshin, MDDirector, Barbara Volcker Center forWomen and Rheumatic DiseasesCo-Director,Mary Kirkland Center for Lupus CareSLE, antiphospholipid syndrome,pregnancy

Emma Jane MacDermott, MD,MRCPIGeneral pediatric rheumatology, childrenwith juvenile arthritis and systemicautoimmune diseases

C. Ronald MacKenzie, MDCo-Director, Center for MusculoskeletalPerioperative MedicinePerioperative care, general rheumatology,ethics

Steven K. Magid, MDGeneral rheumatology, informationtechnology

Carol A. Mancuso, MD, FACPClinical epidemiology

Lisa A. Mandl, MD, MPHClinical epidemiology, osteoarthritis,orthopaedic surgery outcomes

Gina DelGuidice, MDGeneral rheumatology

Stephen J. DiMartino, MD, PhDMyositis, general rheumatology

Doruk Erkan, MD, MPHCo-Director,Mary Kirkland Center for Lupus CareDirector, Lupus Clinical Trials ConsortiumAntiphospholipid syndrome, SLE

Theodore R. Fields, MD, FACPDirector,Rheumatology Faculty Practice PlanClinical Director, Early Arthritis InitiativeCrystalline arthropathies, general rheumatology

Jacobo Futran, MDGeneral rheumatology

Allan Gibofsky, MD, JD, FACP,FCLMCo-Director, Center for InflammatoryArthritis and Innovative Biologic TherapyGeneral rheumatology, genetics,rheumatoid arthritis, spondyl o-arthropathies, Behcet’s disease

Steven R. Goldring, MDChief Scientific OfficerBone biology, rheumatoid arthritis,osteoarthritis, osteolysis research

Susan M. Goodman, MDGeneral rheumatology, perioperative care

Lionel B. Ivashkiv, MDAssociate Chief Scientific OfficerRheumatoid arthritis, SLE research,cytokine, Jak-STAT research

Lawrence J. Kagen, MDMyositis, general rheumatology

DIVISION OFRHEUMATOLOGY

Stephen A. Paget, MD, FACP, FACRPhysician-in-ChiefChairman, Division of RheumatologyCo-Director,Mary Kirkland Center for Lupus ResearchRheumatoid arthritis, SLE, vasculitis

Alexa B. Adams, MDAssociate Director,Pediatric Rheumatology Fellowship Training ProgramPediatrics

Juliet B. Aizer, MD, MPHClinical Scholar EducatorClinical epidemiology, osteoporosis,rheumatoid arthritis, SLE, gout, osteoarthritis

Dalit Ashany, MDGeneral rheumatology

Anne R. Bass, MDDirector,Rheumatology Fellowship ProgramLyme disease, thromboembolic disease

Jessica R. Berman, MDDirector, Resident EducationClinical Scholar Educator General rheumatology

Harry Bienenstock, MDGeneral rheumatology

Richard S. Bockman, MD, PhDMetabolic bone disease

Mary K. Crow, MDDirector, Rheumatology ResearchCo-Director,Mary Kirkland Center for Lupus ResearchSLE, osteoarthritis, atherosclerosisresearch, scleroderma research

PROFESSIONAL STAFF

Lionel B. Ivashkiv, MDLaboratory of Osteolysis Research

Ed Purdue, PhD Laboratory of Steroid HormoneReceptors and Inflammation

Inez Rogatsky, PhDGlucocorticoid signaling

AUTOIMMUNITY ANDINFLAMMATION PROGRAM

Mary K. Crow, MDProgram DirectorSLE research, scleroderma research

Guillermina Girardi, PhDSLE, antiphospholipid research

Kyriakos A. Kirou, MD, FACRSLE, progressive systemic sclerosisresearch

Theresa Lu, MD, PhDLymphoid Tissue Organization andFunction Laboratory

Carol Mancuso, MD, FACPClinical epidemiology

Stephen A. Paget, MD, FACP, FACRRheumatoid arthritis, SLE

Alessandra Pernis, MDSLE, cytokine regulation

Lisa R. Sammaritano, MDSLE, antiphospholipid syndrome,pregnancy

Jane E. Salmon, MDInflammatory Effector MechanismsLaboratory, SLE, antiphospholipidsyndrome, atherosclerosis, pregnancy

Richard Stern, MDGeneral rheumatology

Lisa C. Vasanth, MD, MSClinical epidemiology, early rheumatoid arthritis

Mary Beth Walsh, MDGeneral rheumatology

Evette Weil, MDPerioperative care

Arthur M. Yee, MD, PhDGeneral rheumatology, Raynaud’s phenomenon

Diana A. Yens, MDGeneral rheumatology

RESEARCH DIVISIONLEADERSHIP

Steven R. Goldring, MDChief Scientific OfficerBone biology, rheumatoid arthritis,osteoarthritis, osteolysis research

Lionel B. Ivashkiv, MDAssociate Chief Scientific OfficerJak-STAT, cytokines

Robert N. Hotchkiss, MDDirector, Clinical ResearchHand orthopaedics

ARTHRITIS AND TISSUEDEGENERATION PROGRAM

Carl P. Blobel, MD, PhDProgram DirectorLaboratory of Cellular Signaling andImmune Regulation

Xiaoyu Hu, MD, PhDLaboratory of Cytokine Signaling andInflammation

Joseph A. Markenson, MDRheumatoid arthritis, SLE, clinical trials

Bento R. Mascarenhas, MDGeneral rheumatology

Jacqueline M. Mayo, MDPerioperative care

Charis F. Meng, MDGeneral rheumatology, acupuncture formusculoskeletal pain, older patients withchronic musculoskeletal pain

Sonil S. Parr, MDPerioperative care

Edward J. Parrish, MDGeneral rheumatology, HIV

Jill M. Rieger, MDPerioperative care

Linda A. Russell, MDGeneral rheumatology, metabolic bone disease

Jane E. Salmon, MDCo-Director,Mary Kirkland Center for Lupus ResearchSLE, antiphospholipid syndrome research,atherosclerosis, pregnancy

Lisa R. Sammaritano, MDSLE, antiphospholipid syndrome, pregnancy

Sergio Schwartzman, MDDirector, Center for Inflammatory Arthritis and Innovative Biologic TherapyRheumatoid arthritis, spondyloarthropathy, uveitis

Robert F. Spiera, MDDirector, Vasculitis and SclerodermaProgram and the Rudolf RupertScleroderma Research CenterVasculitis, scleroderma

20

PROFESSIONAL STAFF

21

Invited Speaker, First NationalThrombotic Storm Meeting

Allan Gibofsky, MD, JD, FACP,FCLMReappointment as Special Consultant to

the Arthritis Advisory Committee ofthe Food and Drug Administration

Mary B. Goldring, PhDAlumni Achievement Award, Robert D.

Clark Honors College, University ofOregon

Steven R. Goldring, MDVisiting Scholar, 2008 Annual Clinical

Research Symposium, University ofMichigan Medical School’s Clinicaland Translational Science Center, theMichigan Institute for Clinical andHealth Research

Visiting Professor in Rheumatology,University of Pittsburgh Medical School

Paul Klemperer Award, New YorkAcademy of Medicine

Arthur C. DeGraff Invited Speaker,Department of Medicine AnnualResearch Day, NYU School of Medicine

Recipient, ACR-REF Within Our Reach Innovative Grant

Plenary Speaker, European Societyof Clinical Investigation, Geneva,Switzerland

Speaker and Session Chair, Segal North American Workshop on Osteoarthritis

Thomas J.A. Lehman, MD, FAAP,FACRDistinguished Visiting Expert, Ministry of

Health of the Government of Singapore

Michael D. Lockshin, MDMorris Ziff Distinguished Lecturer in

Rheumatology, Southwestern MedicalCenter, Dallas

Pfizer Visiting Professor, Louisiana State University

Invited Speaker, EuroLupus Project Meeting

AWARDS AND SPECIALRECOGNITION

Juliet B. Aizer, MD, MPHGraduate, Harvard Macy Program for

Educators in the Health Professions

Jessica R. Berman, MDClinician Scholar Educator Award,

American College of Rheumatology

Richard S. Bockman, MD, PhDUnder Dr. Bockman’s mentorship,

Amanda Carmel, MD, received a Mary and David Hoar Fellowship in the Prevention and Treatment of HipFracture

Mary K. Crow, MDKatherine Swan Ginsburg Visiting

Professor, Brigham and Women’sHospital, Boston

Kroc Visiting Professor, UCLAInvited Lecturer, Royal College of

Physicians of IrelandInvited Lecturer, Annual Meeting,

Oligonucleotide Therapeutics SocietyKare Berglund Lecture, Lund University,

SwedenVisiting Professor and Speaker, Medical

Grand Rounds, Emory UniversitySchool of Medicine

Featured Lecturer, Annual Scientific Meeting, American College ofRheumatology

Plenary Lecturer, International Cytokine Society in Montreal, Canada

Doruk Erkan, MD, MPHLupus Research Award, New York

Community TrustRudd-Gardy Teaching Excellence Award,

Division of Rheumatology, Hospital forSpecial Surgery

Speaker, Meet the Professor Session:Antiphospholipid Syndrome, AnnualScientific Meeting, American College ofRheumatology

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 peer-reviewed journals

in the field.

2008-2009 NOTABLE ACHIEVEMENTS

Doruk Erkan, MD, MPHMember, Thrombotic Storm

Classification Committee, First NationalThrombotic Storm Meeting

Theodore R. Fields, MD, FACPMember, Abstract Selection Committee:

Quality Measures and Innovations inPractice Management and Care Delivery,American College of Rheumatology

Allan Gibofsky, MD, JD, FACP,FCLMExecutive Vice President and Member,

Executive Committee, Consortium ofRheumatology Researchers of NorthAmerica (CORRONA)

Member, Executive Committee,International Consensus Program onRheumatoid Arthritis

Secretary-Treasurer, The New York Rheumatism Association

Mary B. Goldring, PhDU.S. Section Head, Cartilage Biology and

Osteoarthritis: Faculty of 1000 Medicine,Rheumatology and Clinical Immunology

Board Member, Osteoarthritis Research Society International (OARSI)

Steven R. Goldring, MDChairman, Research Committee, National

Arthritis FoundationChairman, Basic Science Symposia

Planning Committee, Annual ScientificMeeting, American College of Rheumatology

Member, Nominations and Appointments Committee, American College ofRheumatology

Program Organizer, Segal NorthAmerican Workshop on Osteoarthritis

Co-organizer, Rheumatology Fellows Research Workshop, American Collegeof Rheumatology

Member, Organizing Committee,Second International Conference onOsteoimmunology, Rhodes, Greece

LEADERSHIP POSITIONS

Alexa B. Adams, MDMember, Pediatric Scholarly Oversight

Committee, NewYork-PresbyterianHospital/Weill Cornell Medical Center

Juliet B. Aizer, MD, MPHFellow Representative, American College

of Rheumatology Committee on Education

Scholar Educator, Margaret and Ian Smith Clinical Skills Center, Weill Cornell Medical College

Relevance Reviewer, RheumatologySubspecialty Examination, AmericanBoard of Internal Medicine

Anne R. Bass, MDChairman, Training Resources Subcom-

mittee of the Committee on Workforceand Training, American College ofRheumatology

Jessica R. Berman, MDCore Faculty Member in Teaching and

Coordinator, Subspecialty Education inRheumatology, NewYork-PresbyterianHospital/Weill Cornell Medical Center

Member, Subcommittee on ResidentEducation, American College ofRheumatology

Richard S. Bockman, MD, PhDMember, Professional Practice Committee,

American Society for Bone andMineral Research

Mary K. Crow, MDPresident, Henry Kunkel Society Chair, Scientific Advisory Board, Alliance

for Lupus Research Member, Study Section, Autoimmunity

Centers of Excellence, National Instituteof Allergy and Infectious Diseases

Member, Special Emphasis Panel Review Committee, National Institutes of Health

Michael D. Lockshin, MD (cont.)Invited Speaker, European League

Against Rheumatism (EULAR), Paris, France

Session Co-chair, Fourth International Neuroendocrine Immunology inRheumatic Disease Conference, Santa Margherita, Italy

Invited Speaker, Ninth InternationalConference on Systemic LupusErythematosus, Vancouver (2010)

Jane E. Salmon, MDElected to Association of American

PhysiciansPfizer Visiting Professor, University

of KentuckyPresenter, Research Lecture, 30th Year

Reunion Class, Columbia UniversityCollege of Physicians and Surgeons

Speaker, Seventh European LupusCongress, Amsterdam

Lisa R. Sammaritano, MDFaculty, Antiphospholipid Syndrome,

Rheumatology Review, Course, Harvard Medical School

Faculty, Update Your Medicine: Antiphospholipid Syndrome, Weill Cornell Medical College

Faculty, Updates in Rheumatology(ACINDES): Systemic Lupus Erythe-matosus; Antiphospholipid Syndrome,Madrid, Spain

Faculty, 2009 Update: Antiphospholipid Syndrome, ACR Clinical Symposium,Annual Scientific Meeting, AmericanCollege of Rheumatology

Robert F. Spiera, MDUnder Dr. Spiera’s mentorship, Dr. Jessica

Gordon, senior rheumatology fellow,was awarded the 2009 American Collegeof Rheumatology Distinguished FellowAward

22

2008-2009 NOTABLE ACHIEVEMENTS

23

Michael D. Lockshin, MDEditor-in-Chief, Arthritis & Rheumatism

Jane E. Salmon, MDCo-editor, Arthritis & Rheumatism

Robert F. Spiera, MDAdvisory Editor, Arthritis & RheumatismEditorial Board, Rheumatology News

Robert F. Spiera, MDPresident, New York Rheumatism

AssociationMedical Advisory Board, Vasculitis

FoundationCo-Chair, Medical and Scientific Advisory

Board, Scleroderma Tri-State Chapter

EDITORIAL APPOINTMENTS

Juliet B. Aizer, MD, MPHReviewer, Lupus

Mary K. Crow, MDAssociate Editor, Annals of Rheumatic

Diseases

Doruk Erkan, MD, MPHAdvisory Editor, Arthritis & Rheumatism

Theodore R. Fields, MD, FACPReviewer: Arthritis & Rheumatism,

Arthritis Care and Research

Mary B. Goldring, PhDAssociate Editor, Journal of Cellular

PhysiologyCo-Editor, Arthritis & RheumatismAssociate Editor, Biochimica et Biophysica

Acta: Molecular Basis of DiseaseMember, Board of Associate Editors,

Journal of Orthopaedic ResearchAssociate Editor, Arthritis Research &

Therapy

Thomas J.A. Lehman, MD, FAAP,FACRAssociate Editor, Arthritis & RheumatismSection Editor, Up to Date, Pediatric

RheumatologySection Editor, Current Rheumatology

Reports, Pediatric Rheumatology Author, A Clinician's Guide to Rheumatic

Diseases in Childhood(Oxford University Press)

Thomas J.A. Lehman, MD, FAAP,FACRMember, Medical and Scientific

Committee, Lupus Foundation ofAmerica

Michael D. Lockshin, MDMember, Organizing Committees:

European League Against Rheumatism(EULAR), Copenhagen, 2009; EuropeanWorkshop for Rheumatology Research(EWRR), Warsaw, 2009; the Sixth International Conference on GonadalHormones, Pregnancy and RheumaticDiseases, Lausanne, 2009; and the13th International Congress onAntiphospholipid Antibodies,Galveston, 2010.

Steven K. Magid, MDMember: Chief Medical Information

Officer Leadership Group, DVT/VTEAcademic Collaboration, and OutcomesAdvisory Board, Eclipsys

Member, Medical Informatics of New York Member, Practice Improvement Module

Development Committee and Qualityof Care Subcommittee, American Col-lege of Rheumatology

Lisa A. Mandl, MD, MPHMember, Epidemiology Abstract Review

Committee, Annual Meeting, AmericanCollege of Rheumatology

Jane E. Salmon, MDMember, Scientific Programme

Committee, European League AgainstRheumatism (EULAR)

Participant, Roundtable on Arthritis and Rheumatic Diseases, National Instituteof Arthritis and Musculoskeletal andSkin Diseases (NIAMS)

OSTEOARTHRITIS

Dugar A, Farley ML, Wang AL, Goldring MB, Goldring SR,Swaim BH, Bierbaum BE, Burstein D, Gray ML. The effect ofparaformaldehyde fixation on the delayed gadolinium-enhancedMRI of cartilage (dGEMRIC) measurement. Journal of OrthopaedicResearch 2008; 4:279-286.

Goldring SR. Needs and opportunities in the assessment andtreatment of osteoarthritis of the knee and hip: the view of therheumatologist. The Journal of Bone and Joint Surgery (Am)2009 Feb; 91 Suppl 1:4-6.

Goldring SR. Role of bone in osteoarthritis pathogenesis. Medical Clinics of North America 2009 Jan; 93(1):25-35, xv.

Goldring SR. The role of bone in osteoarthritis pathogenesis.Rheumatic Disease Clinics of North America 2008; 34(3):561-71.

Goodwin JL, Farley ML, Swaim B, Goldring SR, Goldring MB,Bierbaum BE, Gray ML. Dual proline labeling protocol forindividual “baseline” and “response” biosynthesis measurementsin human articular cartilage. Osteoarthritis and Cartilage 2008;16:1263-1266.

Gross KD, Hillstrom H. Knee osteoarthritis: primary care usingnoninvasive devices and biomechanical principles. Medical Clinicsof North America 2009 Jan; 93(1):179-200, xii.

Gross KD, Hillstrom HJ. Noninvasive devices targeting themechanics of osteoarthritis. Rheumatic Disease Clinics ofNorth America 2008 Aug; 34(3):755-76. Review.

Hamamura K, Goldring MB, Yokota H. Involvement of p38MAPK in regulation of MMP13 mRNA in chondrocytes in response to surviving stress to endoplasmic reticulum. Archives of Oral Biology 2009; 54:279-86.

Ijiri K, Zerbini LF, Peng H, Otu HH, Tsuchimochi K, Otero M,Dragomir C, Walsh N, Bierbaum BE, Mattingly D, van Flandern G,Komiya S, Aigner T, Libermann TA, Goldring MB. Differentialexpression of GADD45b in normal and osteoarthritic cartilage:potential role in homeostasis of articular chondrocytes. Arthritis & Rheumatism 2008; 58:2075-2087.

Luan Y, Kong L, Howell DR, Ilalov K, Fajardo M, Bai XH, Di Cesare PE, Goldring MB, Abramson SB, Liu CJ. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilageoligomeric matrix protein by alpha-2-macroglobulin.Osteoarthritis and Cartilage 2008; 16:1413-1420.

Mandl LA, Hotchkiss R, Adler R, Lyman S, Daluiski A, Wolfe S,Katz J. Injectable hyaluronan for the treatment of carpometacarpalosteoarthritis: an open label pilot trial. Current Medical Researchand Opinion. (In press).

METABOLIC BONE DISEASE ANDORTHOPAEDIC BONE HEALTH

Aizer J, Reed G, Harrison MJ. Predictors of bone density testingin patients with rheumatoid arthritis. Rheumatology International(In press).

Bilezikian JP, Matsumoto T, Bellido T, Khosla S, Martin J,Recker RR, Heaney R, Seeman E, Papapoulos S, Goldring SR.Targeting bone remodeling for the treatment of osteoporosis:summary of the proceedings of an ASBMR workshop. Journal of Bone and Mineral Research 2009 Mar; 24(3):373-85.

Cipriano CA, Issack PS, Shindle L, Werner CM, Helfet DL, LaneJM. Recent Advances Toward the Clinical Application of PTH(1-34) in Fracture Healing. HSS Journal: The MusculoskeletalJournal of Hospital for Special Surgery 2009 Mar 17. [Epub aheadof print].

Gehrig LM, Collinge C, Kaufman J, Lane JM, O'Connor MI, Tosi LL.Osteoporosis: management and densitometry for orthopaedicsurgeons. Instructional Course Lectures 2009; 58:805-15.

Gehrig LM, Lane JM, O’Connor MI. Osteoporosis: managementand treatment strategies for orthopaedic surgeons. InstructionalCourse Lectures 2009; 58:817-32.

Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F,Steele B, van der Meulen MC, Lorich DG, Lane JM. Association oflow-energy femoral fractures with prolonged bisphosphonate use:a case control study. Osteoporosis International 2009 Aug;20(8):1353-62. [Epub 2008 Dec 9].

Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, SteinbuchM, Cosman F. Fragility fractures of the hip and femur: incidenceand patient characteristics. Osteoporosis International 2009 May 30.[Epub ahead of print].

Papadopoulos EC, Edobor-Osula F, Gardner MJ, Shindle MK,Lane JM. Unipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures: early results.Journal of Spinal Disorders & Techniques 2008 Dec; 21(8):589-96.

Steele B, Serota A, Helfet DL, Peterson M, Lyman S, Lane JM.Vitamin D deficiency: A common occurrence in both high-andlow-energy fractures. HSS Journal: The Musculoskeletal Journalof Hospital for Special Surgery 2008 Sep; 4(2):143-8.

24

2008-2009 SELECTED PUBLICATIONS

25

Moorthy, LN, Peterson MGE, Hassett AL, Baratelli M, Chalom EC,Hashkes PK, Hong S, Reiff A, Lehman TJA. Relationship betweenhealth-related quality of life and SLE activity and damage inchildren over time. Lupus 2009; 18:622-29.

Moorthy LN, Peterson MGE, Onel KB, Lehman TJA. Do childrenwith lupus have fewer male siblings? Lupus 2008; 17:128-31.

Niewold TB, Adler JE, Glenn SB, Lehman TJA, Harley JB,Crow MK. Age- and sex-related patterns of serum interferon-alphaactivity in lupus families. Arthritis & Rheumatism 2008; 58:2113-9.

Patel AM, Lehman TJA. Rituximab for severe refractory pediatricWegener granulomatosis. Journal of Clinical Rheumatology 2008;14:278-80.

RHEUMATOID ARTHRITIS ANDSPONDYLOARTHROPATHY

Belostocki K, Pricop L, Redecha PB, Aydin A, Leff L, Harrison MJ,Salmon JE. Infliximab treatment shifts the balance betweenstimulatory and inhibitory FcγRII isoforms on neutrophils inrheumatoid arthritis patients. Arthritis & Rheumatism 2008;58:384-388.

Berman J, Krasnokutsky S, Bass A, Fields T, et al. The FifthAnnual New York Rheumatology Objective Structured ClinicalExamination (ROSCE): The Trainee Self-Assessment ofProfessionalism vs. Exam Raters. Arthritis & RheumatismSupplement, September 2008 (Abstract); Arthritis Care andResearch (In press).

Crotti TN, Sharma SM, Fleming JD, Flannery MR, Ostrowski MC,Goldring SR, McHugh KP. PU.1 and NFATc1 mediate osteoclasticinduction of the mouse beta3 integrin promoter. Journal ofCellular Physiology 2008; 215(3):636-44.

Crow MK. Anticyclic citrullinated peptide antibody-negativerheumatoid arthritis: clues to disease pathogenesis. CurrentRheumatology Reports 2008; 10:165-7.

Dastmalchi M, Grundtman C, Alexanderson H, Mavragani CP,Einarsdottir H, Helmers SB, Elvin K, Crow MK, Nenesmo I,Lundberg IE. A high incidence of disease flares in an open pilotstudy of infliximab in patients with refractory inflammatorymyopathies. Annals of the Rheumatic Diseases 2008; 67:1670-7.

Scanzello CR, Moskowitz N, Gibofsky A: The post-NSAID era:what to use now for the pharmacologic treatment of pain andinflammation in osteoarthritis. Current Rheumatology Reports2008; 10:49-56.

Scanzello CR, Plaas A, Crow MK. Innate immune systemactivation in osteoarthritis (OA): is OA a chronic wound? Current Opinion in Rheumatology 2008; 20:565-72.

Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, Dicarlo E,Potter HG, Mandl L, Marx R, Rodeo S, Goldring SR, Crow MK.Local cytokine profiles in knee osteoarthritis: elevated synovialfluid interleukin-15 differentiates early from end-stage disease.Osteoarthritis and Cartilage 2009 Aug; 17(8):1040-8. [Epub 2009Mar 6].

Wang TM, Yen HC, Lu TW, Chen HL, Chang CF, Liu YH, Tsai WC. Bilateral knee osteoarthritis does not affect inter-joint coordination in older adults with gait deviations during obstacle-crossing. Journal of Biomechanics 2009 Aug 11. [Epubahead of print].

Yen HC, Chen HL, Liu MW, Liu HC, Lu TW. Age effects on theinter-joint coordination during obstacle-crossing. Journal ofBiomechanics 2009 Aug 6. [Epub ahead of print].

PEDIATRIC RHEUMATOLOGY

Adams AB, Lehman TJA. Adalimumab therapy for childhooduveitis: a case report. International Journal of Advances inRheumatology 2008; 6(1).

Angeles-Han S, Flynn T, Lehman TJA. Abatacept for refractoryjuvenile idiopathic arthritis-associated uveitis- a case report.The Journal of Rheumatology 2008 Sep; 35(9):1897-8.

Barillas-Arias L, Adams A, Lehman TJA. Pediatric vasculiticsyndromes: Henoch-Schonlein purpura. Consultant forPediatricians 2008 Sept;7(9): 361-367.

Lehman, TJA. Are withdrawal trials in paediatric rheumaticdisease helpful. Lancet 2008 Aug 2; 372(9636):348-50.

MacDermott EJ, Lehman TJA. The role of gene transcriptsignature in diagnosing systemic onset juvenile idiopathicarthritis. Current Rheumatology Reports 2008; 10:133-4.

Moorthy LN, Gaur S, Peterson MG, Landa YF, Tandon M,Lehman TJA. Poststreptococcal reactive arthritis in children: aretrospective study. Clinical Pediatrics (Phila) 2009; 48:174-182.

Moorthy LN, Peterson MG, Harrison MJ, Onel KB, Lehman TJA.Physical function assessment tools in pediatric rheumatology.Pediatric Rheumatology Online Journal 2008; 4:6-9.

Ji JD, Park-Min KH, Ivashkiv LB. Expression and function ofsemaphorin 3A and its receptors in human monocyte-derivedmacrophages. Human Immunology 2009 Apr; 70(4):211-7. [Epub 2009 Feb 7].

Park-Min KH, Ji JD, Antoniv T, Reid AC, Silver RB, Humphrey MB,Nakamura M, Ivashkiv LB. IL-10 suppresses calcium-mediatedcostimulation of receptor activator NF-kappaB signaling duringhuman osteoclast differentiation by inhibiting TREM-2 expression.The Journal of Immunology 2009 Aug 15; 183(4):2444-55. [Epub2009 Jul 22; PubMed - in process].

Rudominer RL, Roman MJ, Devereux RB, Paget SA, Schwartz JE,Lockshin MD, Crow MK, Sammaritano L, Levine DM, Salmon JE.Independent association of rheumatoid arthritis with increasedleft ventricular mass but not with reduced ejection fraction.Arthritis & Rheumatism 2009 Jan; 60(1):22-9.

Salmon JE, Roman MJ. Subclinical atherosclerosis in rheumatoidarthritis. American Journal of Medicine 2008; 121: S3-8.

Sherber NS, Wigley FM, Paget SA. Diffuse fasciitis witheosinophilia developing after local irradiation for breast cancer.Clinical Rheumatology 2009 Jun; 28(6):729-32. [Epub 2009 Feb 18.]

Singer O, Gibofsky A: Review of disease modifying antirheumaticdrug use in rheumatoid arthritis. International Journal ofAdvances in Rheumatology 2009; 6:120-129.

Strober B, Berger E, Cather J, Cohen D, Crowley JJ, Gordon KB,Gottlieb A, Horn EJ, Kavanaugh AF, Korman NJ, Krueger GG,Leonardi CL, Menter A, Schwartzman S, Sobell JM, Young M. A series of critically challenging case scenarios in moderate tosevere psoriasis: a Delphi consensus approach. Journal of theAmerican Academy of Dermatology 2009 Jul; 61(1 Suppl 1):S1-S46.

SYSTEMIC LUPUS ERYTHEMATOSUS/ANTIPHOSPHOLIPID SYNDROME

Aizer J, Karlson EW, Chibnik LB, Costenbader KH, Post D,Liang MH, Gall V, Gerhard-Herman MD. A controlled comparisonof brachial artery flow mediated dilation (FMD) and digital pulseamplitude tonometry (PAT) in the assessment of endothelialfunction in systemic lupus erythematosus. Lupus 2009; 18(3):235-42.

Aringer M, Crow MK. A bridge between interferon-alpha andtumor necrosis factor in lupus. The Journal of Rheumatology 2008;35:1473-6.

Bucciarelli S, Erkan D, Espinosa G, Cervera R. Catastrophic anti-phospholipid syndrome: treatment, prognosis, and the risk ofrelapse. Clinical Reviews in Allergy and Immunology 2009 Jun;36(2-3):80-4. Review.

RHEUMATOID ARTHRITIS ANDSPONDYLOARTHROPATHY (CONT.)

Furst DE, Keystone EC, Kirkham B, Fleischmann R, Meese P,Breedveld FC, Smolen JS, Kalden JR, Burmester GR, Braun J,Emery P, Winthrop K, Bresnihan B, De Benedetti F, Dorner T,Gibofsky A, Schiff MH, Sieper J, Singer N, Van Riel PLCM,Weinblatt ME, Weisman MH: Updated consensus statement on biological agents for the treatment of rheumatic diseases. Annals of the Rheumatic Diseases 2008; 67s3:2-25.

Gibofsky A, Harrington JT: Pay for performance: will we get thecarrot or the stick? Arthritis Care & Research 2008; 9:1203-1206.

Goldring SR. Periarticular bone changes in rheumatoid arthritis:pathophysiological implications and clinical utility. Annals ofthe Rheumatic Diseases 2009 Mar; 68(3):297-9. Annals of theRheumatic Diseases 2009 Jun; 68(6):1080.

Ho HH, Antoniv TT, Ji JD, Ivashkiv LB. Lipopolysaccharide-induced expression of matrix metalloproteinases in human monocytes is suppressed by IFN-gamma via superinduction ofATF-3 and suppression of AP-1. The Journal of Immunology2008 Oct 1; 181(7):5089-97.

Hu X, Chakravarty SD, Ivashkiv LB. Regulation of interferonand toll-like receptor signaling during macrophage activation byopposing feed forward and feedback inhibition mechanisms.Immunological Reviews 2008 Dec; 226:41-56. Review.

Hu X, Chung AY, Wu I, Foldi J, Chen J, Ji JD, Tateya T, Kang YJ,Han J, Gessler M, Kageyama R, Ivashkiv LB. Integrated regulationof Toll-like receptor responses by notch and interferon-gammapathways. Immunity 2008 Nov 14; 29(5):691-703. [Epub 2008 Oct 30].

Hu Y, Park-Min KH, Yarilina A, Ivashkiv LB. Regulation ofSTAT pathways and IRF1 during human dendritic cell maturationby TNF-alpha and PGE2. Journal of Leukocyte Biology 2008 Nov;84(5):1353-60. [Epub 2008 Aug 4].

Ivashkiv LB. A signal-switch hypothesis for cross-regulation ofcytokine and TLR signalling pathways. Nature ReviewsImmunology 2008 Oct; 8(10):816-22.

Ivashkiv LB. Cross-regulation of signaling by ITAM-associatedreceptors. Nature Immunology 2009 Apr; 10(4):340-7. [Epub 2009Mar 19]. Review.

Ji JD, Ivashkiv LB. Roles of semaphorins in the immune andhematopoietic system. Rheumatology International 2009 May;29(7):727-34. [Epub 2009 Jan 13].

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2008-2009 SELECTED PUBLICATIONS

27

of Rheumatology at Hospital for Special Surgery. HSS Journal:The Musculoskeletal Journal of Hospital for Special Surgery.2007 Sep; 3(2):216-21. [Epub 2007 Apr 26].

Gordon JK, Magro C, Lu T, Schneider R, Chiu A, Furman RR,Solomon G, Bass A, Erkan D. Overlap between systemic lupuserythematosus and Kikuchi Fujimoto disease: a clinical pathologyconference held by the Division of Rheumatology at Hospital forSpecial Surgery. HSS Journal: The Musculoskeletal Journalof Hospital for Special Surgery 2009 Jul 16. [Epub ahead of print].

Kariuki SN, Crow MK, Niewold TB. The PTPN22 C1858Tpolymorphism is associated with skewing of cytokine profilestoward high IFN-alpha activity and low tumor necrosis factor-alpha levels in patients with lupus. Arthritis & Rheumatism 2008;58:2818-23.

Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK,Niewold TB. Cutting edge: autoimmune disease risk variant ofSTAT4 confers increased sensitivity to IFN-alpha in lupuspatients in vivo. The Journal of Immunology 2009 Jan 1;182(1):34-8.

Kariuki SN, Moore KA, Kirou KA, Crow MK, Utset TO, Niewold TB.Age- and gender-specific modulation of serum osteopontin and interferon-áby osteopontin genotype in systemic lupus erythematosus. Genes & Immunity [advance online publication2 April 2009].

Kim S, Moskowitz NK, Dicarlo EF, Bass AR, Erkan D, Lockshin MD.Catastrophic antiphospholipid syndrome triggered by sepsis.HSS Journal: The Musculoskeletal Journal of Hospital for SpecialSurgery 2009 Feb; 5(1):67-72. [Epub 2008 Dec 19].

Lockshin MD. Update on antiphospholipid syndrome. Bulletin of the NYU Hospital for Joint Diseases 2008; 66(3):195-7. Review.

Lockshin MD, Derksen RH. New developments in lupus-associatedantiphospholipid syndrome. Lupus 2008; 17(5):443-6. Review.

Lynch AM, Gibbs RS, Murphy JR, Byers T, Neville MC, Giclas PC,Salmon JE, Van Hecke TM, Holers MV. Complement activationfragment Bb in early pregnancy and preterm birth. AmericanJournal of Obstetrics & Gynecology 2008; 199: 354.e1-8.

Lynch AM, Murphy JR, Byers T, Gibbs RS, Neville MC, Giclas PC,Salmon JE, Holers MV. Alternative complement pathwayactivation fragment Bb in early pregnancy as a predictor ofpreeclampsia. American Journal of Obstetrics & Gynecology2008; 198: 385.e1-9 [Epub 28 Jan 2008].

Niewold TB, Adler JE, Lehman TJA, Harley JB, Crow MK. Age- and sex-related patterns of serum interferon alpha activity in lupus families. Arthritis & Rheumatism 2008; 58:2113-9.

Cantaert T, De Rijcke L, Mavragani CP, Wijbrandts CA,Niewold TB, Niers T, Vandooren B, Veys EM, Richel D, Tak PP,Crow MK, Baeten D. Exposure to nuclear antigens contributesto the induction of humoral autoimmunity during TNF alphablockade. Annals of the Rheumatic Diseases 2008 Jul 14 [Epubahead of print].

Cervera R, Bucciarelli S, Plasín MA, Gómez-Puerta JA, Plaza J,Pons-Estel G, Shoenfeld Y, Ingelmo M, Espinos G. CatastrophicAntiphospholipid Syndrome (CAPS) Registry Project Group(European Forum on Antiphospholipid Antibodies). Catastrophicantiphospholipid syndrome (CAPS): descriptive analysis of aseries of 280 patients from the “CAPS registry.” Journal ofAutoimmunity 2009 May-Jun; 32(3-4):240-5. [Epub 2009 Mar 26].

Crow MK. Fast forward for systemic lupus erythematosus clinicaltrials. Nature Clinical Practice Rheumatology 2008; 4:387.

Crow MK, Kirou KA. Interferon-induced versus chemokinetranscripts as lupus biomarkers. Arthritis Research & Therapy2008; 10:126. [Epub 2008 Dec 18].

Cutolo M, Matucci-Cerinic M, Lockshin M, Ostensen M.Introduction: new trends in pregnancy and rheumatic diseases.Rheumatology (Oxford) 2008 Jun; 47 Suppl 3:iii1.

DiMartino SJ, Yuan W, Redecha P, Ivashkiv L, Salmon JE. Insoluble immune complexes are highly effective triggers of IL-10 production in human monocytes and synergize with TLRligands and C5a. Journal of Allergy and Clinical Immunology2008; 127: 56-65.

Doria A, Tincani A, Lockshin M. Challenges of lupus pregnancies.Rheumatology (Oxford). 2008 Jun; 47 Suppl 3:iii9-12.

Erkan D, Lockshin MD. New approaches for managing antiphos-pholipid syndrome. Nature Clinical Practice Rheumatology 2009Mar; 5(3):160-70.

Erkan D, Patel S, Nuzzo M, Gerosa M, Meroni PL, Tincani A,Lockshin MD. Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers. Rheumatology (Oxford). 2008 Jun;47 Suppl 3:iii23-7.

Fernandex DR, Telarico T, Bonilla E, Li Q, Banerjee S, MiddletonFA, Phillips PE, Crow MK, Oess S, Muller-Esterl W, Perl A.Activation of mammalian target of rapamycin controls the lossof TCRzeta in lupus T cells through HRES-1/Rab4-regulatedlysosomal degradation. The Journal of Immunology 2009;182:2063-73.

George D, Vasanth L, Erkan D, Bass A, Salmon J, Lockshin MD.Primary Antiphospholipid Syndrome Presenting as HELLPSyndrome: A Clinical Pathology Conference held by the Division

double-blind, placebo-controlled trial of oral type I collagentreatment in patients with diffuse cutaneous systemic sclerosis:I. Oral type I collagen does not improve skin in all patients, butmay improve skin in late-phase disease. Arthritis & Rheumatism2008 May; 58 (6): 1810-1822.

Spiera RF, Gordon JK, Mehta M, Kirou KA, Lyman S, KloiberSA, Crow MK. Phase IIa trial of Imatnib Mesylate (Gleevec®) inthe treatment of diffuse systemic sclerosis: an interim analysis.Arthritis & Rheumatism 2008 Oct;58 (9):1222, S623-4.

Wung PK, Anderson T, Fontaine KR, Hoffman GS, Specks U,Merkel PA, Spiera R, Davis JC, St.Clair EW, McCune WJ, StoneJH. Effects of glucocorticoids on weight change during the treat-ment of Wegener’s granulomatosis. Arthritis & Rheumatism2008 May; 59 (5): 746-753.

BOOK CHAPTERS

Ashany D, Crow MK. Experimental approaches to the study ofautoimmune rheumatic diseases. In: Essential Clinical Immunology.Edited by J B Zabriskie. Cambridge Medicine 2009; 175-97.

Erkan D. Lockshin MD. Antiphospholipid Syndrome. In: ClinicalImmunology: Principles and Practice, 3rd Edition. Eds. Rich RRet al. Mosby Elsevier, Philadelphia 2008; p: 909-917.

Erkan D, Salmon J, Lockshin MD. Antiphospholipid Syndrome.In: Kelley’s Textbook of Rheumatology, 8th Edition. Eds: RuddyS, Harris ED, Jr., Sledge C. Elsevier Saunders, Philadelphia 2008;p:1301-1310.

Gordon J, Goldenberg D, Erkan D, Lockshin MD. Difficult ClinicalSituations in Antiphospholipid Syndrome. In: Handbook ofSystemic Autoimmune Diseases, Antiphospholipid Syndrome.Ed: Asherson RA, Cervera R. Elsevier, Amsterdam 2009; p:215-234.

Lockshin MD, Salmon J, Erkan D. Pregnancy and RheumaticDisease. In: Creasy and Resnik’s Maternal-Fetal Medicine, 6thEdition. Eds: Creasy RK, Resnik RR, Iams JD, Lockwood CJ,Moore TR. Elsevier, Philadelphia 2008; p1079-1088.

Sammaritano LR. Management of the patient with rheumaticdisease during and after pregnancy. In: Targeted Treatment ofRheumatic Diseases. Michael H. Weisman, Michael E. Weinblatt,James S. Louie and Ronald F. van Vollenhoven. pp 436-455. (In press) 2009, Elsevier (Saunders).

Zabriskie JB, Gibofsky A, Van Voorhis W, Buckner FS, Rose NR:Immunological aspects of cardiac disease. In: Essential ClinicalImmunology. Edited by JB Zabriskie. Cambridge UniversityPress. 2009.

SYSTEMIC LUPUS ERYTHEMATOSUS/ANTIPHOSPHOLIPID SYNDROME (CONT.)

Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with highserum interferon-alpha activity in systemic lupus erythematosuspatients. Arthritis & Rheumatism 2008; 58:2481-7.

Onel KB, Huo D, Hastings D, Fryer-Biggs J, Crow MK, Onel K.Lack of association of the TP53 Arg72Pro SNP and the MDM2SNP309 with systemic lupus erythematosus in Caucasian, AfricanAmerican, and Asian children and adults. Lupus 2009; 18:61-6.

Ostensen M, Lockshin M, Doria A, Valesini G, Meroni P, Gordon C,Brucato A, Tincani A. Update on safety during pregnancy ofbiological agents and some immunosuppressive anti-rheumaticdrugs. Rheumatology (Oxford). 2008 Jun; 47 Suppl 3:iii28-31.

Peerschke EI, Yin W, Alpert DR, Roubey RAS, Salmon JE,Ghebrehiwet B. Serum complement activation on heterologousplatelets is associated with arterial thrombosis in patients withsystemic lupus erythematosus and antiphospholipid antibodies.Lupus 2009; 18: 530-38.

Salmon JE, de Groot P. Pathogenic role of antiphospholipid antibodies. Lupus 2008; 17:405-11.

VASCULITIS AND SCLERODERMA

Chyou S, Ekland EH, Carpenter AC, Tzeng T, Tian S, MichaudM, Madri JA, and Lu TT. Fibroblast-type reticular stromal cellsregulate the lymph node vasculature. Journal of Immunology2008; 181: 3887-3896.

Finkelman J, Merkel P, Schroeder D, Hoffman G, Spiera R,St.Clair W, Davis J, Mccune J, Lears A, Ytterberg S, Hummel A,Viss M, Peikert T, Stone J, Specks U. Glycosylation of proteinase3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis.Clinical and Experimental Rheumatology. On Line: Internet submissionclinexprheumatol.org.

Mahr AD, Neogi T, LaValley MP, Davis JC, Hoffman GS, McCune WJ, Specks U, Spiera RF, St. Clair EW, Stone JH, Merkel PA. Assessment of the Item Selection and Weightingin the Birmingham Vasculitis Activity Score for Wegener’sGranulomatosis (BV AS/WG). Arthritis Care and Research 2008May; 59 (6): 884-891.

Postlethwaite AE, Wong WK, Clements P, Chatterjee S, Fessler BJ,Kang AH, Korn J, Mayes M, Merkel PA, Molitor J, Moreland L,Rothfield N, Simms RW, Smith EA, Spiera R, Steen V, WarringtonK, White B, Wigley F, Furst. A multicenter, randomized,

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2008-2009 SELECTED PUBLICATIONS