Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease (IBD). However, little is known about the effectiveness of topical tacrolimus in this patient population. The aim of this systematic review was to evaluate the current state of literature to evaluate the safety and effectiveness of rectal administration of topical tacrolimus, in the form of suppository, ointment, and/or enema in patients with ulcerative proctitis, perianal Crohn's disease (CD), and chronic refractory pouchitis. ⋯ Topical tacrolimus is effective for a subset of patients with IBD. The adverse effects were minimal and tolerable. Well-designed randomized clinical trials are warranted to establish the appropriate dose and administration method.
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This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription-PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. ⋯ More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.
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High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. ⋯ Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.
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Coccidioidomycosis is a fungal infection of the Western hemisphere that is endemic to the soil in areas with limited rainfall. Human and animal infections result with inhalation of arthroconidia. Most often, this is an asymptomatic event. ⋯ Treatment may not be required for the mildest illness. Azoles are commonly prescribed. Severe infections may require amphotericin B.