Improvement in wrist pain with ultrasound-guided glucocorticoid injections: a meta-analysis of individual patient data.

OBJECTIVES: This meta-analysis compares change in wrist pain following ultrasound-guided (US-guided) intra-articular glucocorticoid injections with change in pain after palpation-guided injections in persons with inflammatory arthritis or osteoarthritis. METHODS: Data sources included MEDLINE, Cochrane, BIOSIS, CINAHL, ACR/AHRP abstracts, and ClinicalTrials.gov. Studies that assessed change in wrist pain with direct comparison of US-guided and palpation-guided injections were included in the meta-analysis. Subject-level data was sought from authors of all relevant studies. Primary outcome was mean change in wrist pain from baseline to 1-6 week follow-up by visual analog scale (VAS). Mean difference in VAS was calculated for comparative studies. Secondary outcome was proportion attaining Minimal Clinically Important Improvement (MCII), defined as VAS reduction ≥ 20%. Odds ratios (ORs) of MCII were calculated for comparative studies. Mean differences in VAS and ORs for MCII for comparative studies were combined using fixed and random effects meta-analysis. RESULTS: Ten studies were eligible, and adequate data was available from 4 studies with direct comparison of US-guided and palpation-guided treatment arms. The difference in mean VAS reduction (US-guided minus palpation-guided) ranged from-0.2 to 1.3, with a combined estimate of 1.0 (95% CI 0.3, 1.7). OR for MCII in comparative studies ranged from 1.0 to 12.4, with a combined OR of 3.2 (95% CI 1.2, 8.5) in favor of ultrasound. CONCLUSIONS: US-guided glucocorticoid injections to the wrist result in greater reductions in pain, and greater likelihood of attaining MCII than palpation-guided injections at 1-6 weeks follow-up.

Killed but metabolically active Leishmania infantum as a novel whole-cell vaccine for visceral leishmaniasis.

There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA L. major and KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasi parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasi parasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasi retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasi correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA L. infantum chagasi displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens.

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted.