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     

淫羊藿、巴戟天中药提取物对恒河猴M0、M1型单核衍生巨噬细胞基因表达的影响

【目的】探讨中药淫羊藿、巴戟天提取物(中药注射液喘可治的组成)对恒河猴单核衍生的巨噬细胞在未极化(M0)、M1极化条件下基因表达的影响,分析其可能的免疫调节的作用机制。【方法】采用密度梯度离心法分离中国恒河猴外周血单个核细胞(PBMCs),采用贴壁法纯化出单核细胞,并以粒细胞巨噬细胞集落刺激因子(GM-CSF)刺激5 d以使单核细胞分化成巨噬细胞;然后不加入极化因子(M0)或以干扰素γ(IFN-γ,继续培养2 d)诱导巨噬细胞极化为M1表型,同时分别加入淫羊藿、巴戟天提取物进行干预;然后提取m RNA并逆转录后,采用实时荧光定量PCR检测CCR5、CD4、CTLA-4、Fox P3、IDO、IL-10、TGF-β等基因表达量。【结果】与空白对照组比较,加入巴戟天提取物培养的M0巨噬细胞基因表达上调不明显;经淫羊藿提取物培养的M0巨噬细胞,CCR5基因表达量上调4.21倍,TGF-β上调7.66倍,Fox P3、IL-10轻度上调,而CD4、CTLA-4、IDO等基因表达改变倍数无明显变化。经巴戟天提取物刺激的M1型巨噬细胞,CTLA-4基因表达量上调3.22倍,Fox P3上调3.69倍,CCR5、CD4、IL-10、IDO基因改变倍数均无明显变化,TGF-β未测出;而由淫羊藿提取物刺激的M1型巨噬细胞,IL-10的表达量上调11.83倍,Fox P3上调4.55倍,IDO、CCR5、CD4、CTLA-4基因改变倍数无明显变化,TGF-β未测出。【结论】巴戟天和淫羊藿提取物培养能够上调M1型巨噬细胞IL-10、Fox P3、CTLA-4等抑炎基因表达,淫羊藿提取物能够上调M0巨噬细胞CCR5和TGF-β等基因表达,促进病原体清除和组织修复,从而发挥多效免疫调节作用。     

血液系统恶性肿瘤患者化疗后合并中性粒细胞减少性肠炎的诊治研究

目的分析成人血液系统恶性肿瘤患者接受强烈化疗后中性粒细胞减少性肠炎（NE）的发生率、危险因素及预后情况。方法收集2004至2013年接受化疗的1804例血液系统恶性肿瘤患者，记录患者血常规、凝血检测和血液生化检测结果，并记录患者年龄、性别、原发病、既往化疗次数、既往化疗方案中是否使用阿糖胞苷、临床症状、肠壁厚度、中性粒细胞最低计数、中性粒细胞缺乏持续时间、NE的治疗方法和预后等，探讨NE起病诱因、临床特征、腹部B超特点、症状的预后意义及化疗药物对发病的影响等。结果1804例患者中226例（12.5%）化疗后合并NE，化疗后10~19d起病，中位起病时间为化疗后第14天。发生NE后26例患者死亡，病死率11.5%。化疗药物包括阿糖胞苷、临床症状≥4项、中性粒细胞缺乏持续超过7d以及B超下肠壁厚度≥10mm的患者病死率相对较高。结论NE是接受强烈化疗的血液系统肿瘤患者的严重的并发症，发生NE后患者病死率较高。     

伊伐布雷丁在心血管疾病中的现状与进展

降低心率可能成为心血管疾病治疗的新靶标,伊伐布雷定可通过特异性地抑制If起搏电流通过降低窦房结节律而减慢心率,目前在心血管疾病领域取得了一定的进展,现对其临床应用进行综述。     

氧合指数与急性呼吸衰竭行有创通气治疗患者预后的关系

目的探讨氧合指数与急性呼吸衰竭行有创通气治疗患者预后的关系。方法选取2008年1月至2012年10月山东省即墨市人民医院行有创通气治疗急性呼吸衰竭患者75例,其中死亡28例,设为死亡组,存活47例,设为存活组;比较两组患者行有创通气治疗前急性生理与慢性健康状况(APACHE)Ⅲ评分、多器官功能障碍综合征(MODS)评分,治疗1、3、7 d后氧合指数(Pa O2/Fi O2)、动脉血二氧化碳分压(Pa CO2)及p H值等血气分析指标水平。结果存活组和死亡组患者行有创通气治疗前急性生理学与慢性健康状况评分Ⅲ(APACHEⅢ)评分和多器官功能障碍综合征(MODS)评分组间比较差异无统计学意义(P>0.05);存活组和死亡组患者治疗1 d后Pa O2/Fi O2、Pa CO2及p H水平组间比较差异无统计学意义(P>0.05);两组患者治疗3、7 d后Pa CO2和p H水平组间比较差异无统计学意义(P>0.05);但死亡组患者治疗3、7 d后Pa O2/Fi O2水平明显低于存活组(P<0.05);存活组和死亡组在治疗后不同时间(1、3、7 d)的Pa O2/Fi O2和Pa CO2比较差异有统计学意义(P<0.05)。结论氧合指数与急性呼吸衰竭行有创通气治疗患者预后关系密切,可作为临床评价重要参考指标之一。     

Clinical analysis of high-intensity focussed ultrasound ablation for abdominal wall endometriosis: a 4-year experience at a specialty gynecological institution

Objective: To evaluate the long-term clinical effect of high-intensity focussed ultrasound (HIFU) as a non-invasive modality for ablation of abdominal wall endometriosis (AWE) foci.

Methods: All women who were diagnosed with cutaneous endometriosis and underwent HIFU ablation and 4-year follow-up were included. Patient symptoms, imaging performed, HIFU ablation, recurrence, lesion location, size and number were collected and analyzed.

Results: A total of 51 women with 57 painful abdominal wall masses with a median volume of 4.00?cm³ and a mean age of 30.5±2.12 years were treated with HIFU. The main symptoms were a palpable painful abdominal mass (93%), protrusion of the skin (28.1%, 16) or lack of protrusion of the skin (71.9%, 41). Ultrasound was initially performed in 100% (51) of women, whereas 6% (3) required MRI examinations to distinguish the features and range of the masses. Ablation was performed with a median 300?s of sonication time, 40?min treatment time, 150?W of power and 41800?J of total energy to treat lesions that were a median volume of 3.83?cm³. No severe complications occurred, except in one patient with a first-degree skin burn, during the 48-month follow-up period. The pooled recurrence of cutaneous endometriosis occurred in 3.9% (2) of women.

Conclusion: The diagnosis of AWE should be confirmed with imaging of the lesion number, location, size and features before HIFU ablation. HIFU should be the first choice for the treatment of AWE as it is a non-invasive method, with high efficiency and safety and rapid postoperative recovery.     

新型冠状病毒肺炎出院患者生活质量及影响因素研究

目的:了解新型冠状病毒肺炎(COVID-19)患者出院后的生活质量及其影响因素,为优化早期干预方案,预防社区生活受限,制定相应社区康复措施提供依据。方法:选择2020年3—4月在武汉华润武钢总医院治愈出院的COVID-19患者57例,于2020年4—5月通过"问卷星"平台采用简明健康状况调查量表(SF-12V2)调查患者的生活质量;采用焦虑自评量表(SAS)调查患者的焦虑状态;采用抑郁自评量表(SDS)调查患者的抑郁状态;采用呼吸困难指数量表(mMRC)调查患者的呼吸困难程度。比较不同特征COVID-19患者生活质量的差异;分析患者生活质量与焦虑、抑郁和呼吸困难程度的相关性及其相关的影响因素。结果:共发放57份调查问卷,剔除重复及无效问卷3份,获得有效问卷54份,问卷有效率达94.74%。(1)COVID-19出院后患者生活质量情况:生理总评分和心理总评分分别为(37.02±12.32)分、(38.46±14.42)分;呼吸困难等级0~3级的分别为3例(5.56%)、45例(83.33%)、5例(9.26%)、1例(1.85%);有19例(35.19%)存在焦虑情绪(SAS≥50分)和抑郁情绪(SDS≥53分)。(2)不同特征COVID-19患者生活质量比较:不同疾病分型的患者在生理总评分方面差异有统计学意义(P<0.05)。(3)生活质量与焦虑、抑郁和呼吸困难程度的相关性分析:Pearson相关分析结果显示,SF-12V2生理总评分与焦虑程度(r=-0.34,P=0.011)和呼吸困难程度(r=-0.39,P=0.003)之间存在负相关性,SF-12V2心理总评分与焦虑程度(r=-0.46,P=0.001)和抑郁程度(r=-0.40,P=0.002)之间存在负相关性。(4)COVID-19患者生活质量的影响因素分析:多元线性回归分析显示,性别(β=8.27)、抑郁程度(β=-0.34)和疾病分型(β=-11.68)是患者SF-12V2生理总评分的重要决定因素(P<0.05);焦虑程度(β=-0.62)是患者SF-12V2心理总评分的重要决定因素(P<0.05)。结论:COVID-19出院患者存在呼吸困难、焦虑抑郁情绪和生活质量下降的问题;性别、疾病分型、抑郁程度和焦虑程度是COVID-19患者生活质量下降的重要因素。COVID-19患者(特别是女性患者和重型患者)出院后要尽早进行抑郁症和焦虑症的筛查和干预,减少患者负性情绪,鼓励患者适当参与康复训练,提高呼吸功能,从而促进生活质量提高。     

Improvements in epidermal function prevent relapse of psoriasis: a self‐controlled study

While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self‐controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in‐house‐prepared emollient or ATOPALM^® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis.