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Revealing How Steroids Work GRIP1 Required
Inez Rogatsky, PhD, and her lab discovered that without GRIP1, glucocorticoids (GC) fail to control inflammation. The team found that without GRIP1, the GC receptors on macrophages fail to repress NFkB activity. Transcription is “on”, pro-inflammatory cytokines keep being produced. Until now, the key molecular mechanisms of how GC stop inflamation had not been known.
Inez Rogatsky, PhD, HSS Associate Scientist
The Role of Transcriptional Coregulator Glucocorticoid hormone Receptor Interacting Protein-1 (GRIP1) in the Anti-inflammatory Actions of Glucocorticoids (GC)
Published in PNAS, July, 2012 Full Details now on HSS.edu
HSS Authors: Yurii Chinenov, PhD Rebecca Gupte Jana Dobrovolna, PhD Jamie R. Flammer, PhD Bill Liu Francesco E. Michelassi Inez Rogatsky, PhD next study
How JAK Inhibitors Stop Inflammation in Rheumatoid Arthritis
Lionel B. Ivashkiv MD Associate Chief Scientific Officer
It has not been completely understood exactly how JAK inhibitors suppress inflammation in RA. Now, an HSS study of two JAK inhibitors (tofacitinib and ruxolitinib) has revealed key mocleular mechanisms. The drugs are able to suppress macrophage activation and attenuate tumor necrosis factor (TNF) responses. Cytokine/chemokine production is diminished.
Regulation of Inflammatory Responses in Tumor Necrosis Factor-activated and RA Synovial Macrophages by Janus Kinase Inhibitors
Published in Arthritis & Rheumatism, (epub in advance of print) August, 2012. Authors
the 20 years or so I have been studyingHSS: Anna Yarilina MD, PhD The research team also found that Kai Xu inhibitors partially interfered with ulation ofJAKinflammation, this seems to be Chunhin Chan factor NF-KB, blocking the Lionel B. Ivashkiv MD the mosttranscription potent inhibitory mechanism expression of genes that encode proFull details on HSS.edu cytokines. we haveinflammatory ever seen.
â€“ Lionel Ivashkiv, MD, Associate Chief Scientific Officer,
New Discovery: Key Mechanism of Negative Regulation of Osteoclastgenesis
Steven A. Goldring, MD Chief Scientific Officer Richard L. Menschel Research Chair
Lionel B. Ivashkiv, MD Associate Chief Scientific Officer David M. Koch Chair
Edward Purdue, PhD HSS Associate Scientist Director, HSS Osteolysis Lab
The molecular mechanisms that directly suppress osteoclastogenesis have not been well understood. Now, a recent collaboration has uncovered a key finding In the study, CD11b suppressed induction of NFATc1 by the complementary mechanisms of downregulation of RANK expression and induction of recruitment of the transcriptional repressor BCL6 to the NFATC1 gene. CD11b was identified as a negative regulator of the earliest stages of osteoclast differentiation.
Negative Regulation of Osteoclast Precursor Differentiation by CD11band Î˛2 integrin-BCL6 Signaling.
Published in Journal of Bone Mineral Research, (Epub ahead of print) August, 2012 Coming Soon: Full details on HSS.edu
Authors HSS: Neal K Moskowitz, MD, PhD Elisha Lim Edward Purdue, PhD Steven R Goldring, MD Lionel B Ivashkiv, MD University of Connecticut Health Center: Sun-Kyeong Lee, PhD Joseph A Lorenzo, MD HSS and Seoul National University College of Medicine: Kyung-Hyun Park-Min, MD Eun Young Lee Weill Cornell Medical College: Chuanxin Huang, PhD Ari M Melnick, MD
New, Non-invasive Test May Help Diagnose Pulmonary Hypertension in Scleroderma
(left to right) Robert F. Spiera, MD Jessica K. Gordon, MD, MSc Lisa A. Mandl, MD, MPH
A new, noninvasive stress test called SHAPE™ that uses a 5.5 inch high step on which patients step up and down for 3 minutes has showed promising results for use in diagnosing pulmonary hypertension (PH) in scleroderma. End tidal carbon dioxide monitored during SHAPE™ had significant negative correlation to the mPAP of right heart catherization (RHC), the current gold standard diagnostic test. RHC is both expensive and invasive. SHAPE™ stands for Submaximal Heart And Pulmonary Evaluation. Further, wider studies will help determine how SHAPE™ can help non-invasively diagnose PH, a leading cause of death in SSc.
Authors from HSS: Elana J. Bernstein, MD Jessica K. Gordon, MD, MSc Robert F. Spiera, MD Lisa A. Mandl, MD, MPH Evelyn M. Horn, MD Presented at the 2012 ACR Annual Meeting
Full details on HSS.edu
Michael A. Lockshin, MD Director, Barbara Volcker Center for Women and Rheumatic Disease; Co-director, Mary Kirkland Center for Lupus Research at HSS
Jane E. Salmon, MD Collette Kean Research Chair; Co-director, Mary Kirkland Center for Lupus Research at HSS
LAC Strongest Indicator of Advese Outcome in aPL-Associated Pregnancies PROMISSE Study Overturns Common Belief The presence of lupus anticoagulant (LAC) is the primary predictor of adverse pregnancy outcome after 12 weeks’ gestation in aPL-associated pregnancies. Other antibodies in the same family, thought to cause pregnancy complications, do not put women at increased risk. Anticardiolipin antibody and anti-β2 GPI – if LAC is not also present – do not predict adverse pregnancy outcome. These findings are from the first clinical research publication of PROMISSE – the largest ever study of pregnancy outcomes in women with lupus and/or aPL.
Published in Arthritis & Rheumatism, July 2012. Full Details on study and PROMISSE on HSS.edu
Testing New Drugs to Treat SSc: Results of Open Label Trials of Imatinib Mesylate (Gleevec™) Systemic sclerosis (SSc) – or scleroderma – has many debilitating manifestations and few reliably effective treatments. Research at HSS is hoping to help change that. Clinical trials at HSS have been testing the tyrosine kinase inhibitor (TKI) Imatinib Mesylate (Gleevec™) to treat SSc. At the 2012 ACR Annual Meeting, HSS doctors are reporting on a 24-month trial extension involving 17 patients with early diffuse SSc. The patients had already completed an initial 12-month trial. The target daily dose of 400mg of Gleevec™ was the same in both trials. The group started the extension with a median Modified Rodnan Skin Score (MRSS) score of 24, which reflected a 22% average improvement from the first 12 month trial. At the end of the 24-month extension, the median group MRSS had improved to 18. Results must be interpreted cautiously, as patients with SSc can have spontaneous improvements in their skin scores, especially with longer duration of disease. While both trials showed acceptable safety and tolerability, adverse events did occur. Imantinib is a powerful drug and is not for everyone. Testing at HSS has been a long, careful process. Further, wider testing is warranted on a drug that can provide some benefit for some people, especially when so few alternatives exist. Robert F. Spiera, MD HSS Attending Rheumatologist Director, HSS Vasculitis and Scleroderma Program
HSS Authors: Jessica K. Gordon, MD Morgana L. Davids Kamini Doobay
Jamie N. Mersten Stephen L. Lyman, PhD Mary K. Crow, MD Robert F. Spiera, MD
Full Details now on HSS.edu
New Findings on Joint Replacement for Patients with SLE or RA HSS Rheumatologists & Orthopedic Surgeons Overturn Common Beliefs Recent collaborations of HSS physicians and surgeons using the extensive HSS Total Joint Replacement Registries have revealed that patients with lupus and RA can experience pain relief and beneficial results from total joint arthroplasty (TJA). Drug treatments for RA have changed dramatically in recent years, and the investigators wanted to see if that change affected patient outcomes in joint replacement. Matching each of 159 contemporary patients with RA having total knee replacement (TKR) to two patients undergoing TKR for osteoarthritis (OA), the collaboration demonstrated that patients with RA can expect TKR benefits and outcomes similar to patients with OA. Another investigation matched each of 101 patients with lupus undergoing either TKR or total hip arthroplasty (THA) to two similar patients having the same surgery for OA. Patients with lupus experienced far fewer adverse events than previously expected. Two years after surgery, pain and function outcomes were similiar for patients with and without lupus. Studies presented at the 2012 ACR Annual Meeting HSS Authors, Both Studies: Lisa A. Mandl MD MPH (right) Assistant Attending Physician Susan M Goodman, MD (left) Assistant Attending Physician Mark P. Figgie, MD (pictured on next page) Chief, Surgical Arthritis Service Additonal Authors and Full Details on HSS.edu
Morbid Obesity is Not a Risk Factor for Poor Pain and Function Two Years After Total Knee Replacement Almost 90% of referring physicians think obesity increases the likelihood of poor outcomes after total knee replacement (TKR). However, current data are conflicting. A recent collaboration of HSS rheumatologists and orthopedic surgeons found that although obese patients have worse pain and function at the time they elect TKR, their outcomes at 2 years are not clinically significantly different than other patients. However, race and educational attainment were significantly associated with poor outcomes. The study anaylzed data from 2524 patients in the HSS Total Joint Replacement Registry who underwent TKR between 2007 and 2009. Findings showed that obese patients have similar expectations and are as satisfied as patients with lower BMI. While more research is needed on the effect of race and education on TKR outcomes, morbid obesity should not be regarded as a risk factor for poor outcomes after primary TKR. Authors HSS: Susan M. Goodman, MD Mark P. Figgie, MD, Alejandro Gonzalez Della Valle, MD Michael M. Alexiades, MD Lisa A. Mandl MD, MPH Presented at 2012 ACR Annual Meeting Full details on HSS.edu Mark P. Figgie, MD Chief, Surgical Arthritis Service
Alejandro Gonzalez Della Valle, MD Associate Attending Orthopaedic Surgeon
Pilot Nutrition Education Program Receives High Marks from Culturally Diverse Teens with Lupus and their Families
A recent HSS study shows promising results for a hospital-based education program specially designed for a culturally diverse group of teens with lupus and their families to learn about healthy nutrition together. The curriculum focused on learning about the nutritional benefits of whole grains/fiber, calcium/ vitamin D, fruits/vegetables, protein foods, and snacks/ fast foods. Several key topics were included throughout all 5 sessions, including portion control, food labels, sodium and culturally appropriate recipe examples.
Authors HSS: Jillian A. Rose, LMSW (above left) Roberta Horton, LCSW, ACSW (above right) Dariana M. Pichardo Dana Friedman, MPH Robyn Wiesel, CHES Sandra Goldsmith, MA, MS, RD Sotiria Everett, MS, RD, CDN, CSSD Morgan Stanley Childrenâ€™s Hospital, New York-PresbyterianColumbia University Medical Center: Lisa F. Imundo, MD
94% of participants rated overall content as excellent. 94% of the participants reported that the program led them to include more nutritious foods in their diet. The benefits of this pilot series will be further expanded in future programs, which will consider adding more communication tools and social media.
Presented by Jillian Rose, LMSW, at 2012 ACR Annual Meeting Full details on HSS.edu
Test of a Systematic Two Drug Regimen Shows Prolonged Improvement in Lupus A carefully supervised, systematic regimen of two powerful drugs was found to significantly reduce steroid dosage while improving a patientâ€™s lupus condition. 15 patients, ranging in age from 10 to 22, with active lupus, who had been dependent on steroids for control of the condition, received a systematic regimen of rituximab and cyclophosphamide administered at three intervals â€“ at the start of the trial, then again at 6 months, and a third time at 18 months. All 15 patients experienced improvements in 6 standard indicators of lupus disease level in their blood tests. Note these powerful drugs, used in chemotherapy, must not be administered without careful supervision from doctors familiar with the medications.
Thomas J.A. Lehman, MD Chief, Pediatric Rheumatology
Study presented by Dr. Lehman at 2012 ACR Annual Meeting Full Details Coming Soon to HSS.edu
Authors: HSS: Thomas J. A. Lehman, MD Emily Baird Anusha Ramanathan, MD Risa Alperin, MD Emma J. MacDermott, MD Alexa B. Adams, MD Maimonides Medical Center: Laura V. Barinstein, MD Robert Wood Johnson-UMDNJ: Lakshmi N. Moorthy, MD
Patient Self-Assessments and Patient Reported Outcomes May Reliably Identify Disease Flare in Early RA Patients reporting a rheumatoid arthritis (RA) flare have clinical indices reflecting worsening disease activity. Using criteria of pain, function, stiffness, coping, participation, and fatigue, patient reported outcomes (PROs) significantly discriminated between patients reporting flare vs. no flare. These findings were uncovered in a recent investigation involving data from 512 patients in the CATCH (Canadian early ArThritis CoHort) study, comparing patient and doctor assessment of symptoms and clinical status in a flare. There is modest agreement between patients and MDs regarding flare status. Flare patients identify more swollen and tender joints than MDs. PROs and patient joint counts may reliably identify disease flare, but some ratings are higher in patients than MDs. More research is needed to identify predictors of concordance and discrepancy between patients and providers in flare assessment.
Study presented by Dr. Bykerk at the 2012 ACR Annual Meeting
Vivian P. Bykerk, BSc, MD, FRCPC
Authors HSS: Vivian P. Bykerk, BSc, MD, FRCPC Johns Hopkins University: Clifton O. Bingham III, MD Cardiff University School of Medicine, UK: Ernest Choy, MD, FRCP Mount Sinai Hospital, Toronto: Juan Xiong, PhD CHUS - Sherbrooke University, Quebec: Gilles Boire, MD, MSc University of Manitoba, Winnipeg: Carol A. Hitchon, MD, FRCPC, MSc University of Western Ontario: Janet E. Pope, MD, MPH, FRCPC Southlake Regional Health Centre, Ontario: J. Carter Thorne, MD, FRCPC University of Montreal Hospital Research Centre: Boulos Haraoui, MD, FRCPC University of Toronto: Edward Keystone, MD, FRCPC McGill University, Montreal: Susan J. Bartlett, PhD
Full Details With Chart of Patient/MD Concordances Coming soon to HSS.edu
Hospital-Based Exercise Program Shown to Decrease Pain and Improve Life for Patients with Arthritis Low cost, community exercise programs can play an important role in fighting OA with minimal resources.
Authors HSS: Sandra Goldsmith, MA MS RD Dana Friedman, MPH Linda Roberts, LCSW Dana Sperber Laura Robbins, DSW, CSW, MSW Linda Russell, MD Presented at the 2012 ACR Annual Meeting
Full details on HSS.edu
A recent HSS study has shown that a low-cost, hospital-based, exercise program of weekly classes significantly decreased pain and the severity and frequency of falls, as well as improved enjoyment of life and balance among the participants. Of the 200 study participants, 53% indicated pain relief. Further analysis showed that in a subet of 66 participants who complete both pre and post program surveys, 62% experienced pain relief. Pain intensity dropped from 4.5 to 2.7 with 0 being “no pain” and 10 “worst pain imaginable. Weekly classes, part of the HSS Osteoarthritis Wellness Initiative, included Tai Chi, yoga, mat and chair pilates, yoga-lates and dance fitness. Instructors tailored programs where necessary for patients with osteoarthritis.
Testing New Drugs for SSc: A Single Group, Open Label, Pilot Clinical Trial of Nilotinib (Tasignaâ„˘) Second generation tyrosine kinase inhibitor (TKI) drugs aim to be more efficacious with less side effects. A recent pilot study of one such TKI called nilotinib (Tasignaâ„˘) was completed by 7 patients with diffuse cutaneous (dc) systemic sclerosis (SSc) for less than 3 years. The twice daily 400 mg oral dose of nilotinib was tolerated by the majority of patients in the study. Tolerability was limited primarily by mildly prolonged QTc, which is a known side effect of nilotinib and an exclusion criterion for continuation in this study. Modified Rodnan Skin Score (MRSS) improved significantly with 6 months of treatment in this very early and active group of patients. Further testing in randomized placebo controlled trials will ultimately be necessary to determine whether the benefits seen were truly related to the medication tested. Full Details on HSS.edu
Authors HSS: Jessica K. Gordon, MD Morgana L. Davids Kamini Doobay Stephen L. Lyman, PhD Mary K. Crow, MD Robert F. Spiera, MD Weill-Cornell Medical Center: Cynthia Magro, MD Horatio F. Wildman, MD Presented by Dr. Gordon (pictured) at the 2012 ACR Annual Meeting
Full Details on HSS.edu
Stories of Health & Humanity Coming Soon from HSS A New, Online, Narrative Journal By and For People Living with Rheumatic Conditions and their Physicians and Caregivers Rheum to Heal will use the power of words and images, combined with the nurturing balm of community, to transform all who share them. The frequently common emotional impact back to page 1
of chronic rheumatic disease, once creatively expressed, has the ability to unite and heal.
Stories, Poems, Artwork, Healing from patients, doctors & caregivers
Learn more about the HSS Rheumatology Research Studies presented at the 2012 ACR Meeting.