Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

腰硬联合镇痛及患者自控镇痛对产程及分娩结局的影响

目的 探讨腰硬联合(CSEA)及患者自控镇痛(PCEA)对产程及分娩结局的影响。方法 随机选取2014年1~12月足月待产、无妊娠合并症和并发症初产妇996例,其中503例产妇于活跃期实施CSEA+PCEA镇痛(分娩镇痛组),493例未行分娩镇痛(对照组),分别记录并比较两组产妇各产程时间、子宫收缩、镇痛效果、运动神经阻滞程度、产程中缩宫素的使用率、产后出血率、羊水Ⅲ度污染率、新生儿Apgar评分、产钳助产和剖宫产率。结果 分娩镇痛组第一产程、第二产程较对照组有所延长,差异有统计学意义(P<0.05);第三产程无明显改变;子宫收缩力减弱;分娩镇痛组较对照组镇痛效果显著,差异有统计学意义(P<0.05);运动阻滞程度低;缩宫素使用率、产后出血率、羊水Ⅲ度污染率、及新生儿Apgar评分及产钳助产和剖宫产率两组比较,差异均无统计学意义(P>0.05)。结论 腰硬联合分娩镇痛可能会使第一产程、第二产程延长,对子宫收缩力有一定的影响,但并未增加缩宫素的使用率及产钳助产和剖宫产率,其镇痛效果显著,运动阻滞程度低,对分娩结局无不良影响。     

羽毛球运动中发生手腕和肩袖损伤的相关因素调查

目的：通过对羽毛球爱好者的问卷调查，结合羽毛球项目的运动特点，分析常见的运动损伤部位及其发病原因、处理方法以及预防措施. 方法：调查于2005—03／11在成都医学院体育教研室羽毛球俱乐部完成，对156名羽毛球爱好者进行运动损伤情况凋查，均自愿参加调查。采用问卷调查和专家访谈相结合的方法，主要结合羽毛球项目的运动特点，调查运动损伤的患病率、损伤类型及其受伤原因，分析其常用的处理方法及预防措施。 结果：共发放问卷156份，收回内容详实问卷156份。（1）损伤患病率：运动损伤患病率为78，84％。（2）损伤类型：156名羽毛球爱好者中急性损伤占52、56％，慢性损伤占26，28％。最容易受伤的手腕处受伤患病率为37．39％，其次是肩袖受伤患病率为30．89％。（3）受伤原因：技术动作不规范是运动损伤最主要的原因，占72，35％，而准备活动不充分和身体疲劳分别占63、41％和22．76％. 结论：为有效预防手腕和肩袖损伤，应加强局部肌肉力量训练等防治措施；注意学习和掌握正确的动作技术要领，做好充分的准备活动是十分必要的.     

57例胎膜早破的临床分析

目的探讨胎膜早破与剖宫产及母儿并发症的关系。方法对本院2004年~2005年分娩的898例产妇资料进行回顾性分析,其中胎膜早破组57例,对照组(胎膜未破)841例,对两组进行总体成数假设检验。结果胎膜早破组羊膜腔感染率、早产率、子宫内膜炎发生率均较对照组显著升高(P<0.01),但剖宫产率、新生儿成活率、产后出血率两组间无显著差异(P>0.01)。结论胎膜早破与羊膜腔感染综合征、早产、子宫内膜炎成因果关系,与剖宫产、新生儿成活、产后出血无必然的因果关系。故及时应用抗生素,适时促胎肺成熟,适时终止妊娠,合理选择分娩方式,可以使胎膜早破者不会提高剖宫产率、产后出血率、新生儿死亡率,但对于胎膜早破者需及时、有效、合理选择广谱抗生素,降低羊膜腔感染和子宫内膜炎发生率,降低早产率。