Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab.

How is radiating leg pain defined in randomized controlled trials of conservative treatments in primary care? A systematic review.

Many terms exist to describe radiating leg pain or symptoms associated with back pain (e.g., sciatica or radiculopathy) and it appears that these terms are used inconsistently. We examined the terms used to describe, and the eligibility criteria used to define, radiating leg pain in randomized controlled trials of conservative treatments, and evaluated how the eligibility criteria compared to an international pain taxonomy. Eligible studies were identified from two systematic reviews and an updated search of their search strategy. Studies were included if they recruited adults with radiating leg pain associated with back pain. Two independent reviewers screened the studies and extracted data. Studies were grouped according to the terms used to describe radiating leg pain. Thirty-one of the seventy-seven included studies used multiple terms to describe radiating leg pain; the most commonly used terms were sciatica (60 studies) and disc herniation (19 studies). Most studies that used the term sciatica included pain distribution in the eligibility criteria, but studies were inconsistent in including signs (e.g., neurological deficits) and imaging findings. Similarly, studies that used other terms to describe radiating leg pain used inconsistent eligibility criteria between studies and to the pain taxonomy, except that positive imaging findings were required for almost all studies that used disc herniation to describe radiating leg pain. In view of the varying terms to describe, and eligibility criteria to define, radiating leg pain, consensus needs to be reached for each of communication and comparison between studies.

Systematic review of prognostic factors predicting outcome in non-surgically treated patients with sciatica.

Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non-surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non-surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery.