Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.     

Estimation of phase signal change in neuronal current MRI for evoke response of tactile detection with realistic somatosensory laminar network model

Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm³. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation.     

后外侧结构重建在新鲜股骨颈骨折人工股骨头置换术中的应用

目的探讨后外侧结构重建对后外侧入路人工股骨头置换术术后早期关节脱位的影响。方法选取2016年9月至2017年8月于我院行后外侧入路初次人工股骨头置换术的股骨颈骨折患者60例,根据术中是否修补关节囊及外旋肌群分为重建组(33例:舌形切开关节囊,术中将关节囊及外旋肌群原位缝合在大转子后方及臀中肌肌腱附着处)和对照组(27例:切除关节囊后,术中未进行外旋肌群修复重建)。比较两组的手术情况及术后近期关节功能情况。结果重建组的手术时间为(45.0±15.3) min,长于对照组的(35.0±12.4) min (P <0.05)。重建组术腔引流量为(200.0±80.0) m L,少于对照组的(420.0±120.6) m L (P <0.05)。重建组的早期脱位率为0.000%(0例),与对照组的7.407%(2例)比较无统计学差异(P>0.05)。重建组术后Harris评分为(92.0±3.4)分,高于对照组的(88.2±5.0)分(P <0.05)。结论在后外侧入路人工股骨头置换过程中行后外侧结构重建能够有效减少术腔引流量,提高髋关节Harris评分,对维持髋关节软组织平衡具有重要意义。     

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。