Jessica Berman

TNF-α Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss

The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, intrauterine growth restriction, and vascular thrombosis in the presence of antiphospholipid (aPL) Abs. Our studies in a murine model of APS induced by passive transfer of human aPL Abs have shown that activation of complement and recruitment of neutrophils into decidua are required for fetal loss, and emphasize the importance of inflammation in aPL Ab-induced pregnancy loss. In this study, we examine the role of TNF-α in pregnancy complications associated with aPL Abs in a murine model of APS. We show that aPL Abs are specifically targeted to decidual tissue and cause a rapid increase in decidual and systemic TNF-α levels. We identify the release of TNF-α as a critical intermediate that acts downstream of C5 activation, based on the fetal protective effects of TNF-α deficiency and TNF blockade and on the absence of increased TNF-α levels in C5-deficient mice treated with aPL Abs. Our results suggest that TNF-α links pathogenic aPL Abs to fetal damage and identify TNF blockade as a potential therapy for the pregnancy complications of APS.

Nested case-control study of selected systemic autoimmune diseases in World Trade Center rescue/recovery workers.

To test the a priori hypothesis that acute and chronic work exposures to the World Trade Center (WTC) site on or after September 11, 2001 were associated with risk of new‐onset systemic autoimmune diseases.

Post–September 11, 2001, Incidence of Systemic Autoimmune Diseases in World Trade Center–Exposed Firefighters and Emergency Medical Service Workers

OBJECTIVE To estimate the incidence of selected systemic autoimmune diseases (SAIDs) in approximately 14,000 male rescue/recovery workers enrolled in the Fire Department of the City of New York (FDNY) World Trade Center (WTC) Health Program and to compare FDNY incidence to rates from demographically similar men in the Rochester Epidemiology Project (REP), a population-based database in Olmsted County, Minnesota. PATIENTS AND METHODS We calculated incidence for specific SAIDs (rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and others) and combined SAIDs diagnosed from September 12, 2001, through September 11, 2014, and generated expected sex- and age-specific rates based on REP rates. Rates were stratified by level of WTC exposure (higher vs lower). Standardized incidence ratios (SIRs), which are the ratios of the observed number of cases in the FDNY group to the expected number of cases based on REP rates, and 95% CIs were calculated. RESULTS We identified 97 SAID cases. Overall, FDNY rates were not significantly different from expected rates (SIR, 0.97; 95% CI, 0.77-1.21). However, the lower WTC exposure group had 9.9 fewer cases than expected, whereas the higher WTC exposure group had 7.7 excess cases. CONCLUSION Most studies indicate that the healthy worker effect reduces the association between exposure and outcome by about 20%, which we observed in the lower WTC exposure group. Overall rates masked differences in incidence by level of WTC exposure, especially because the higher WTC exposure group was relatively small. Continued surveillance for early detection of SAIDs in high WTC exposure populations is required to identify and treat exposure-related adverse effects.

Validity and Reliability of Patient Reported Outcomes Measurement Information System Computerized Adaptive Tests in Systemic Lupus Erythematosus

Objective. The aims of this study were to assess the construct validity and the test-retest reliability of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive tests (CAT) in patients with systemic lupus erythematosus (SLE). Methods. Adults with SLE completed the Medical Outcomes Study Short Form-36, LupusQoL-US version (“legacy instruments”), and 14 selected PROMIS CAT. Using Spearman correlations, PROMIS CAT were compared with similar domains measured with legacy instruments. CAT were also correlated with the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) disease activity and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores. Test-retest reliability was evaluated using ICC. Results. There were 204 outpatients with SLE enrolled in the study and 162 completed a retest. PROMIS CAT showed good performance characteristics and moderate to strong correlations with similar domains in the 2 legacy instruments (r = −0.49 to 0.86, p < 0.001). However, correlations between PROMIS CAT and the SELENA-SLEDAI disease activity and SDI were generally weak and statistically insignificant. PROMIS CAT test-retest ICC were good to excellent, ranging from 0.72 to 0.88. Conclusion. To our knowledge, these data are the first to show that PROMIS CAT are valid and reliable for many SLE-relevant domains. Importantly, PROMIS scores did not correlate well with physician-derived measures. This disconnect between objective signs and symptoms and the subjective patient disease experience underscores the crucial need to integrate patient-reported outcomes into clinical care to ensure optimal disease management.

Refractory sarcoid arthritis in World Trade Center-exposed New York City firefighters: a case series.

ObjectiveThe objective of this study was to describe cases of sarcoid arthritis in firefighters from the Fire Department of the City of New York (FDNY) who worked at the World Trade Center (WTC) site. MethodsAll WTC-exposed FDNY firefighters with sarcoidosis and related chronic inflammatory arthritis (n = 11) are followed jointly by the FDNY-WTC Health Program and the Rheumatology Division at the Hospital for Special Surgery. Diagnoses of sarcoidosis were based on clinical, radiographic, and pathological criteria. Patient characteristics, WTC exposure information, smoking status, date of diagnosis, and pulmonary findings were obtained from FDNY-WTC database. Joint manifestations (symptoms and duration, distribution of joints involved), radiographic findings, and treatment responses were obtained from chart review. ResultsNine of 60 FDNY firefighters who developed sarcoidosis since 9/11/2001 presented with polyarticular arthritis. Two others diagnosed pre-9/11/2001 developed sarcoid arthritis after WTC exposure. All 11 were never cigarette smokers, and all performed rescue/recovery at the WTC site within 3 days of the attacks. All had biopsy-proven pulmonary sarcoidosis, and all required additional disease-modifying antirheumatic drugs for adequate control (stepwise progression from hydroxychloroquine to methotrexate to anti–tumor necrosis factor &agr; agents) of their joint manifestations. ConclusionsChronic inflammatory polyarthritis appears to be an important manifestation of sarcoidosis in FDNY firefighters with sarcoidosis and WTC exposure. Their arthritis is chronic and, unlike arthritis in non–WTC-exposed sarcoid patients, inadequately responsive to conventional oral disease-modifying antirheumatic drugs, often requiring anti–tumor necrosis factor &agr; agents. Further studies are needed to determine the generalizability of these findings to other groups with varying levels of WTC exposure or with other occupational/environmental exposures.

Creating an Academy of Medical Educators: How and Where to Start

BackgroundWhile most faculty members want to improve as teachers, they neither know where their educational strengths and weaknesses lie nor where or how to begin to effect a change in their teaching abilities. The lack of actionable, directed and specific feedback, and sensible and sensitive metrics to assess performance and improvement complicates the attainment of educational excellence.PurposeThe purpose of this article was to outline a series of specific steps that medical education programs can take to enhance the quality of teaching, promote teaching excellence, elevate the status and value of medical educators, and stimulate the creation of innovative teaching programs and curricula.MethodsTo achieve these goals at the Hospital for Special Surgery, the Academy of Rheumatology Medical Educators was formed. The academy had the following goals: (1) create within our institution a mission which advances and supports educators, (2) establish a membership composed of distinguished educators, (3) create a formal organizational structure with designated leadership, (4) dedicate resources that fund mission-related initiatives and research, and (5) establish a plan for promoting teachers as well as enhancing and advancing educational scholarship.ResultsThe Hospital for Special Surgery Academy of Rheumatology Medical Educators was recently formed to address these goals by promoting teaching and learning of musculoskeletal skills in an environment that is supportive to educators and trainees and provides much needed resources for teachers.SummaryThe development of a pilot academy of medical educators represents one of the high-priority goals of those institutions that wish to elevate and enrich their teaching through a structured, proven approach.

Building a Rheumatology Education Academy: Insights from Assessment of Needs During a Rheumatology Division Retreat

Objective. To implement a rheumatology department education retreat to systematically identify and address the key factors necessary to improve medical education in our division in preparation for developing a rheumatology academy. Methods. The Hospital for Special Surgery organized a retreat for the Rheumatology Department aimed at (1) providing formal didactics and (2) assessing participants’ self-reported skills and interest in education with the goal of directing this information toward formalizing improvement. In a mixed-methods study design, faculty and fellows in the Division of Rheumatology were surveyed online pre- and post-retreat regarding various aspects of the current education program, their teaching abilities, interest and time spent in teaching, divisional resources allocated, and how education is valued. Results. Enthusiasm for teaching was high before and rose further after the retreat. Confidence in abilities was higher than expected before but fell afterward. Many noted that the lack of specific feedback on teaching skills and useful metrics to assess performance prevented the achievement of educational excellence. Most responding felt lack of time, knowledge of how to teach well, and resources prevented them from making greater commitments to educational endeavors and participating fully and effectively in the department’s teaching activities. Conclusion. While most rheumatology faculty members want to improve as teachers, they know neither where their educational strengths and weaknesses lie nor where or how to begin to change their teaching abilities. The key elements for an academy would thus be an educational environment that elevates the quality of teaching throughout the division and promotes teaching careers and education research, and raises the importance and quality of teaching to equivalence with clinical care and research.

Feasibility, Validity, and Reliability of the 10-item Patient Reported Outcomes Measurement Information System Global Health Short Form in Outpatients with Systemic Lupus Erythematosus

Objective. To assess the feasibility, validity, and reliability of the Patient Reported Outcomes Measurement Information System Global Health Short Form (PROMIS10) in outpatients with systemic lupus erythematosus (SLE). Methods. SLE outpatients completed PROMIS10, Medical Outcomes Study Short Form-36 (SF-36), LupusQoL-US, and selected PROMIS computerized adaptive tests (CAT) at routine visits at an SLE Center of Excellence. Construct validity was evaluated by correlating PROMIS10 physical and mental health scores with PROMIS CAT, legacy instruments, and physician-derived measures of disease activity and damage. Test-retest reliability was determined among subjects reporting stable SLE activity at 2 assessments 1 week apart using intraclass correlation coefficients (ICC). Results. A diverse cohort of 204 out of 238 patients with SLE (86%) completed survey instruments. PROMIS10 physical health scores strongly correlated with physical function, pain, and social health domains in PROMIS CAT, SF-36, and LupusQoL, while mental health scores strongly correlated with PROMIS depression CAT, SF-36, and LupusQoL mental health domains (Spearman correlations ≥ 0.70). Active arthritis, comorbid fibromyalgia (FM), and anxiety were associated with worse PROMIS10 scores, but sociodemographic factors and physician-assessed flare status were not. Test-retest reliability for PROMIS10 physical and mental health scores was high (ICC ≥ 0.85). PROMIS10 required < 2 minutes to complete. Conclusion. PROMIS10 is valid and reliable, and can efficiently screen for impaired physical function, pain, and emotional distress in outpatients with SLE. With strong correlations to LupusQoL and SF-36 but significantly reduced responder burden, PROMIS10 is a promising tool for measuring patient-reported outcomes in routine SLE clinical care and value-based healthcare initiatives.

Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen Years Promoting Rheumatology Educators and Education

The Rheumatology Research Foundations Clinician Scholar Educator (CSE) award is a 3‐year career development award supporting medical education research while providing opportunities for mentorship and collaboration. Our objective was to document the individual and institutional impact of the award since its inception, as well as its promise to strengthen the subspecialty of rheumatology.

Reply: To PMID 25779102

To the Editor: We read with interest the article by Webber et al (1) in which they addressed an important issue, i.e., exposure to environmental agents playing a potential role in the development of systemic autoimmune diseases. Exposure to aerosolized “World Trade Center dust,” which, as the authors stated, contains an amalgam of pulverized cement, glass fibers, silica, asbestos, lead, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polychlorinated furans and dioxins, resulted in a high and time-dependent percentage of systemic autoimmune diseases, taking into account the results of the reported nested case–control study. Among the 59 patients with systemic autoimmune disease described by the authors, inflammatory myopathies were diagnosed in 8 (6 patients with polymyositis and 2 with dermatomyositis). Given that occupational exposure seems to play a role in patients with myositis and antisynthetase antibodies (2,3) (the so-called antisynthetsase syndrome), it would be of interest to know how many of those 8 patients with myositis were positive for any of the most frequent antisynthetase antibodies (anti–Jo-1, anti–PL-7, or anti– PL-12). If this was the case, these data will undoubtedly reinforce the notion that exposure to inhaled antigens could act as a precipitating event in these patients.