Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.     

Percutaneous and surgical tracheostomy in critically ill adult patients: a meta-analysis

Introduction

The aim of this study was to conduct a meta-analysis to determine whether percutaneous tracheostomy (PT) techniques are advantageous over surgical tracheostomy (ST), and if one PT technique is superior to the others.

Methods

Computerized databases (1966 to 2013) were searched for randomized controlled trials (RCTs) reporting complications as predefined endpoints and comparing PT and ST and among the different PT techniques in mechanically ventilated adult critically ill patients. Odds ratios (OR) and mean differences (MD) with 95% confidence interval (CI), and I² values were estimated.

Results

Fourteen RCTs tested PT techniques versus ST in 973 patients. PT techniques were performed faster (MD, −13.06 minutes (95% CI, −19.37 to −6.76 (P <0.0001)); I² = 97% (P <0.00001)) and reduced odds for stoma inflammation (OR, 0.38 (95% CI, 0.19 to 0.76 (P = 0.006)); I² = 2% (P = 0.36)), and infection (OR, 0.22 (95% CI, 0.11 to 0.41 (P <0.00001)); I² = 0% (P = 0.54)), but increased odds for procedural technical difficulties (OR, 4.58 (95% CI, 2.21 to 9.47 (P <0.0001)); I² = 0% (P = 0.63)). PT techniques reduced odds for postprocedural major bleeding (OR, 0.39 (95% CI, 0.15 to 0.97 (P = 0.04)); I² = 0% (P = 0.69)), but not when a single RCT using translaryngeal tracheostomy was excluded (OR, 0.58 (95% CI, 0.21 to 1.63 (P = 0.30)); I² = 0% (P = 0.89)). Eight RCTs compared different PT techniques in 700 patients. Multiple (MDT) and single step (SSDT) dilatator techniques are associated with the lowest odds for difficult dilatation or cannula insertion (OR, 0.30 (95% CI, 0.12 to 0.80 (P = 0.02)); I² = 56% (P = 0.03)) and major intraprocedural bleeding (OR, 0.29 (95% CI, 0.10 to 0.85 (P = 0.02)); I² = 0% (P = 0.72)), compared to the guide wire dilatation forceps technique.

Conclusion

In critically ill adult patients, PT techniques can be performed faster and reduce stoma inflammation and infection but are associated with increased technical difficulties when compared to ST. Among PT techniques, MDT and SSDT were associated with the lowest intraprocedural risks and seem to be preferable.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0544-7) contains supplementary material, which is available to authorized users.     

利拉鲁肽对RNAi介导的脂联素基因抑制ApoE基因敲除小鼠糖脂代谢的影响

目的 探讨利拉鲁肽对脂联素基因表达缺陷的ApoE基因敲除(ApoE-/-)小鼠糖脂代谢的影响.方法 采用静脉葡萄糖耐量试验(IVGTT)评价利拉鲁肽的量效关系.利用扩展高胰岛素钳夹技术评价各组小鼠糖脂代谢和胰岛素敏感性变化.结果 在IVGTT中,利拉鲁肽1 mg/kg组,糖负荷后5、15和30 min血糖值均明显低于其它剂量组(均P＜0.01),而血浆胰岛素水平在5、15 min均明显高于其他3组(均P＜0.01).联合注射利拉鲁肽和脂联素RNAi腺病毒组体重、空腹血糖、血浆游离脂肪酸、总胆固醇、甘油三酯、血浆胰岛素和低密度脂蛋白胆固醇(LDL-C)水平显著低于脂联素RNAi腺病毒组(P＜0.05或P＜0.01),而高密度脂蛋白胆固醇(HDL-C)则明显高于脂联素RNAi组(P＜0.05).钳夹稳态时,脂联素RNAi组血浆胰岛素明显高于利拉鲁肽组(P＜0.01),游离脂肪酸、总胆固醇、甘油三酯虽被抑制,但仍明显高于利拉鲁肽组(P＜0.05).利拉鲁肽组葡萄糖输注率(GIR)则明显高于脂联素RNAi组(P＜0.01).钳夹结束时,脂联素RNAi组葡萄糖清除率(GRd)明显低于利拉鲁肽组(P＜0.01),而肝糖输出率则明显高于利拉鲁肽组(P＜0.01).结论 长期的利拉鲁肽干预上调了脂联素基因表达缺陷ApoE-/-小鼠血浆脂联素水平,并改善了其胰岛素抵抗.     

Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus

BACKGROUND: Obestatin is a novel hormone that is encoded by the Ghrelin gene and produced in the gut. Ghrelin is profoundly orexogenic and adipogenic, increasing food intake and body weight. This new ghrelin-associated peptide behaves as a physiological opponent of ghrelin in rodent animals, but its pathophysiological role in humans remains unknown OBJECTIVE: In this study we investigate whether plasma obestatin level is different in patients with impaired glucose regulation (IGR) and type 2 diabetes mellitus (T2DM). PATIENTS AND MEASUREMENTS: Forty-seven patients with T2DMu, 30 subjects with IGR, and 38 sex- and age-matched normal controls participated in the study. Plasma obestatin levels were measured with a radioimmunoassay. The relationship between plasma obestatin levels and anthropometric and metabolic parameters was also analysed. RESULTS: Plasma obestatin levels were lower in patients with T2DM and IGR than in controls (37.5 +/- 9.2 ng/l and 39.2 +/- 9.7 ng/l vs. 43.8 +/- 8.0 ng/l, P = 0.002 and P = 0.039, respectively). Decreasing concentrations of obestatin were independently and significantly associated with IGR and T2DM. Multiple logistic regression analysis revealed obestatin to be independently associated with IGR and T2DM. In a multiple linear regression analysis, only waist-to-hip ratio and homeostasis model assessment of insulin resistance (HOMA-IR) were independently associated with plasma obestatin level. CONCLUSION: Our results suggest that obestatin may play a role in appetite regulation in patients with IGR and T2DM.     

Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy

PURPOSE: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)-na?ve patients with breast cancer-related bone metastases. EXPERIMENTAL DESIGN: Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks). RESULTS: At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were -73% and -75% for the pooled denosumab groups and -79% and -71% for the IV BP group. Among patients with > or =1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP-treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP-treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred. CONCLUSIONS: In IV BP-na?ve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.