Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I ² 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I ² 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I ² 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I ² = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I ² = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.     

Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus

Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor-prognosis subset of patients with esophageal cancer.     

Healing of root resorption: a case report

External resorption is sequelae of necrotic periodontal membrane over a large area of root following an injury to the tooth. This usually occurs after severe dental injuries such as intrusion, severe luxations or exarticulation injuries complicated by a prolonged extra oral period. This case report presents a clinical and radiographic follow up (13 months) of treatment of inflammatory external root resorption on maxillary central incisor using Vitapex. Gradual healing of resorption was observed radiographically with no tenderness or pathological mobility.     

Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model

The chemopreventive efficacy of toremifene, an antiestrogen, was evaluated in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP mice were segregated into three groups: (a) the low-dose toremifene group (6.6 mg/kg/day); (b) the high-dose toremifene group (33 mg/kg/day); and (c) the control placebo group. Efficacy of treatment was measured by the absence of palpable tumor. To extend these studies using more sensitive techniques, TRAMP mice were then treated with placebo, flutamide (an antiandrogen; 33 mg/kg/day), or toremifene (10 mg/kg/day). Animals from each treatment group were sacrificed at 7, 10, 15, 20, 25, and 30 weeks of age, and prostate tissues and seminal vesicles were harvested. Tissues from animals (n = 5) in each group were evaluated by wholemount dissections of genitourinary tracts, histology, immunohistochemistry, and Western blot analyses. Blood was pooled per group to measure estradiol and testosterone hormonal levels. Tumors formed at week 17 in the placebo group (n = 10), at week 21 in the high-dose toremifene group (n = 12), and at week 29 in the low-dose toremifene group (n = 12). This represents an increased tumor latency of up to 12 weeks. By 33 weeks, all animals in the placebo group had tumors compared with only 35% of the animals treated with toremifene. Although both flutamide and toremifene decreased tumor incidence compared with the placebo, toremifene was more effective than flutamide. High-grade prostatic intraepithelial neoplasia was observed in animals in the placebo group, but not in animals treated with toremifene. Moreover, toremifene-treated animals had prolonged survival compared with placebo-treated animals. By 33 weeks of age, 100% of the placebo-treated animals had developed palpable tumors and died, whereas 60% of the toremifene-treated animals were tumor free. T antigen levels in the prostate of toremifene-treated animals were similar to those of placebo-treated, age-matched animals. Whereas serum estradiol levels remained unchanged, the total and free testosterone levels were elevated in the toremifene-treated group. Toremifene treatment did not affect androgen receptor levels. Because toremifene prevented prostate cancer in a milieu of elevated blood free testosterone levels with no change in prostate androgen receptor expression, the mechanism of toremifene's chemopreventive activity may be through nonandrogenic pathways, such as estrogen receptor signaling.     

Neurostimulation systems for deep brain stimulation: in vitro evaluation of magnetic resonance imaging-related heating at 1.5 tesla

PURPOSE: To assess magnetic resonance imaging (MRI)-related heating for a neurostimulation system (Activa Tremor Control System, Medtronic, Minneapolis, MN) used for chronic deep brain stimulation (DBS). MATERIALS AND METHODS: Different configurations were evaluated for bilateral neurostimulators (Soletra Model 7426), extensions, and leads to assess worst-case and clinically relevant positioning scenarios. In vitro testing was performed using a 1.5-T/64-MHz MR system and a gel-filled phantom designed to approximate the head and upper torso of a human subject. MRI was conducted using the transmit/receive body and transmit/receive head radio frequency (RF) coils. Various levels of RF energy were applied with the transmit/receive body (whole-body averaged specific absorption rate (SAR); range, 0.98-3.90 W/kg) and transmit/receive head (whole-body averaged SAR; range, 0.07-0.24 W/kg) coils. A fluoroptic thermometry system was used to record temperatures at multiple locations before (1 minute) and during (15 minutes) MRI. RESULTS: Using the body RF coil, the highest temperature changes ranged from 2.5 degrees-25.3 degrees C. Using the head RF coil, the highest temperature changes ranged from 2.3 degrees-7.1 degrees C.Thus, these findings indicated that substantial heating occurs under certain conditions, while others produce relatively minor, physiologically inconsequential temperature increases. CONCLUSION: The temperature increases were dependent on the type of RF coil, level of SAR used, and how the lead wires were positioned. Notably, the use of clinically relevant positioning techniques for the neurostimulation system and low SARs commonly used for imaging the brain generated little heating. Based on this information, MR safety guidelines are provided. These observations are restricted to the tested neurostimulation system.     

Intrapartum oxytocin use for labor acceleration in rural India

Objective: To examine factors associated with the use of oxytocin for acceleration of labor in women delivered at home in rural India. Method: Quantitative data were collected from 527 women who were delivered at home and qualitative interviews were carried out with 21 mothers and 9 birth attendants. Results: Oxytocin use was associated with higher education and socioeconomic status, primigravidity, and delivery by a traditional birth attendant. Conclusion: Labor acceleration with oxytocin occurs indiscriminately In India. Oxytocin use should be regulated, and training for birth attendants should be provided as well as health education for pregnant women.