Bulletin of the NYU hospital for joint diseases最新文献

Objective: Review of the literature addressing the rheumatic manifestations of various malignancies as well as of common chemotherapeutic agents.

Methods: A literature search was performed to identify key articles regarding the association of rheumatic disease with malignancy.

Results: Our review focused on the association of rheumatic disease with malignancy, paraneoplastic syndromes with rheumatic manifestations, and chemotherapeutic agents related to rheumatic syndromes. We have discussed the importance of a newly described autoantibody that may identify patients at risk for malignancy associated myositis.

Conclusion: Based on our literature review, recommendations are suggested regarding who and how patients should be screened for malignancy when presenting with various rheumatic symptoms.

All physicians are faced at some time with fundamental challenges while striving to respect the principle canons which define a physician's ethical code. These canons are: 1. Primacy of patient interests, 2. Patient confidentiality, 3, Informed consent, and 4. Maintenance of a high standard of care. Athletes, because of their focus on performance, often present unique situations which lead to ethical challenges not seen in the general patient population. Adherence to the four principle ethical canons guides physicians to make ethical decisions when dealing with these unique patients.

Kinase inhibitors have now been shown to work in various types of patients and have potential to be additional weapons in our armamentarium in rheumatoid arthritis treatment. This review will go over the currently available data and discuss potential uses for these new agents.

Despite over 60 years of use, glucocorticoids continue to be a controversial therapy in rheumatoid arthritis (RA). This stems largely from their measured a well as their perceived toxicity. However, a paucity of top tier evidence from clinical trials or very carefully controlled observational studies leads to limited evidence supporting potential causal relations between low-dose glucocorticoids and adverse outcomes. Several new studies have contributed to an improved understanding of these associations and they are reviewed here along with highlights from the older body of literature examining these important outcomes.

B cells were originally considered key mediators in the pathogenesis of rheumatoid arthritis (RA). The presence of these cells in many RA synovial tissues and the discovery of rheumatoid factor had put B cells originally at the center of disease pathogenesis. That enthusiasm vanished shortly thereafter only to resurface in the last 15 years with the appearance of highly specific anti-cyclic citullinated protein antibodies. Rituximab, an anti-CD20 antibody that depletes mature B cells, was approved for the treatment of RA in 2006. Since then, B cell depletion strategies have proven efficacy for advanced disease, particularly in those patients that do not respond to DMARDs or TNFα inhibitors.

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) that are prescribed for treatment of osteoarthritis (OA) symptoms including pain and inflammation target the production eicosanoids which exhibit numerous functions in various cell types. In these studies, we have (a) identified the diverse eicosanoid pathways that are activated in human chondrocytes of normal and OA cartilage, (b) delineated the modulation of eicosanoids in the presence of NSAIDS and selective COX-2 inhibitors, and (c) characterized eicosanoid products and various transcripts modulated by various inhibitors of eicosanoids in human OA cartilage by gene expression arrays.

Methods: Immunoassay analysis of culture supernatants were utilized to determine the spectrum of eicosanoids derived from both the cyclooxygenase (COX) and lipoxygenase (LOX) pathways of normal and human OA cartilage in ex-vivo conditions. Human OA cartilage was incubated in ex-vivo conditions to examine spontaneous or IL-1 induced production of eicosanoids in the presence of various COX inhibitors. Gene expression analysis was performed to analyze the expression of mRNA in the presence and absence of COX-2 inhibitors in OA cartilage in ex-vivo conditions.

Results: Normal and OA human cartilage explants produced multiple eicosanoids of the COX and LOX pathways. PGF1α, PGF2α, PGE2 > TXB2, PGD2, and LTB4 were spontaneously generated by normal and OA cartilage. Among these, elevated levels of PGE2 and LTB4 were generated in OA as compared to normal cartilage. IL-1 treatment further enhanced these eicosanoids production. Treatment of OA cartilage explants with cyclooxygenase inhibitors (celecoxib & indomethacin) augmented LTB4 accumulation by 2- to 4-fold. A follow-up pharmacogenomic analysis identified approximately 90 cytokine and growth factor related transcripts that were modulated following selective COX-2 inhibition.

Conclusion: These studies for the first time demonstrate that normal and OA cartilage generates multiple and differential eicosanoid products. Inhibition of the COX- pathway in human OA cartilage caused accumulation of end products (LTB4) of the 5LO pathway. Furthermore, celecoxib, a selective COX-2 inhibitor, regulated numerous genes in cartilage, which are linked to the NFkB and AP-1 pathways at the mRNA level. In conclusion, these experiments demonstrate the complex and pleotropic role of eicosanoids in human cartilage homeostasis and pathophysiology of OA.

Hamstring injuries are a frequent injury in athletes. Proximal injuries are common, ranging from strain to complete tear. Strains are managed nonoperatively, with rest followed by progressive stretching and strengthening. Reinjury is a concern. High grade complete tears are better managed surgically, with reattachment to the injured tendon or ischial tuberosity. Distal hamstring injury is usually associated with other knee injuries, and isolated injury is rare.

Glucocorticoids form a mainstay of therapy for rheumatoid arthritis (RA) and other conditions since they exert strong anti-inflammatory, immunosuppressive, and disease-modifying therapeutic effects. However, there is increasing awareness of the potential for these drugs to produce adverse effects. Therefore, improvement of the glucocorticoid benefit-risk ratio represents both a current need and an ongoing challenge. The development of recommendations to implement a more effective and safer use of these important drugs is one useful path to pursue. An additional avenue is the development of innovative glucocorticoids or glucocorticoid receptor ligands. Also, treatment with conventional glucocorticoid preparations currently available to clinicians may be improved. The most advanced development in the latter regard is a novel chronotherapeutic prednisone formulation called delayed- release (DR) or modified-release prednisone. The CAPRA (Circadian Administration of Prednisone in Rheumatoid Arthritis) studies confirmed that optimizing the timing of GC administration improves the benefit-risk ratio of long- term low dose glucocorticoid treatment in patients with rheumatoid arthritis. DR prednisone has been approved in 16 European countries as well as Australia and Israel. Very recently, DR prednisone was also approved in the United States to treat rheumatologic conditions such as RA, polymyalgia rheumatica and psoriatic arthritis, as well as respiratory conditions such as COPD and asthma.

In a follow-up study, patients are monitored over time. Longitudinal and time-to-event studies are the two most important types of a follow-up study. In this paper, the focus is on longitudinal studies with a continuous response where patients are examined at several time points. While longitudinal studies provide a powerful tool for the evaluation of a treatment effect over time, a major problem is missing data caused, for example, by patients who drop out from the study. Many longitudinal studies in rheumatology use inappropriate statistical methodology because either they do not address correctly the correlated nature of the repeated measurements, or they treat the problem of missing data incorrectly. We will illustrate that there are interpretational and computational issues with the "classical" approaches. Further, we expand here on more appropriate statistical techniques to analyze longitudinal studies. To this end, we focus on randomized controlled trials (RCTs) and illustrate the approaches on data from a fictive randomized controlled trial in rheumatology.