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Use of a train-of-four ratio of 0.95 versus 0.9 for tracheal extubation: an exploratory analysis of POPULAR data.

使用 0.95 与 0.9 的四列比用于气管拔管: 流行数据的探索性分析。

  • 影响因子:2.83
  • DOI:10.1016/j.bja.2019.08.023
  • 作者列表:"Blobner M","Hunter JM","Meistelman C","Hoeft A","Hollmann MW","Kirmeier E","Lewald H","Ulm K
  • 发表时间:2020-01-01
Abstract

BACKGROUND:The prospective observational European multicentre cohort study (POPULAR) of postoperative pulmonary complications (NCT01865513) did not demonstrate that adherence to the recommended train-of-four ratio (TOFR) of 0.9 before extubation was associated with better pulmonary outcomes from the first postoperative day up to hospital discharge. We re-analysed the POPULAR data as to whether there existed a better threshold for TOFR recovery before extubation to reduce postoperative pulmonary complications in patients who had quantitative neuromuscular monitoring (87% acceleromyography). METHODS:To identify the optimal TOFR, the complete case cohort of patients with quantitative neuromuscular monitoring (n=3150) was split into several pairs of sub-cohorts related to TOFR values from 0.86 to 0.96; values of 0.97 and higher could not be used as the sub-cohorts were too small. The optimal TOFR was considered to have the lowest P-value from multivariate logistic regression calculated for each of the TOFR values. Data are presented as adjusted absolute risk reduction or median difference with 95% confidence interval. RESULTS:Extubating patients with TOFR >0.95 rather than >0.9 reduced the adjusted risk of postoperative pulmonary complications by 3.5% (0.7-6.0%) from that reported in POPULAR (11.3%). Increasing the recommended TOFR from 0.9 to 0.95 reduced the adjusted risk by 4.9% (1.2-8.5%). Sub-cohorts resulting from 1:1 propensity score matching revealed that sugammadex had been given in higher doses by 0.30 (0.13-0.48) mg kg-1 in the sub-cohort with TOFR > 0.95. CONCLUSIONS:A post hoc analysis of patients receiving quantitative monitoring of neuromuscular function suggests that postoperative pulmonary complications are reduced for TOFR > 0.95 before tracheal extubation compared with TOFR > 0.9. TRIAL REGISTRATION NUMBER:NCT01865513.

摘要

背景: 术后肺部并发症的前瞻性观察性欧洲多中心队列研究 (POPULAR) (NCT01865513) 并没有证明遵守推荐的四联比 (TOFR) 拔管前的 0.9 与术后第一天至出院时更好的肺部结局相关。我们重新分析了接受定量神经肌肉监测 (87% 加速肌动造影) 的患者拔管前 TOFR 恢复是否存在更好的阈值以减少术后肺部并发症的流行数据。 方法: 确定最佳 TOFR,定量神经肌肉监测患者的完整病例队列 (n = 3150) 分成几对与 TOFR 值相关的子队列,从 0.86 到 0.96; 0.97 及更高的值不能使用,因为子队列太小。从多变量 logistic 回归中计算每个 TOFR 值的最佳 TOFR 被认为具有最低的 P 值。数据显示为调整后的绝对风险降低或 95% 置信区间的中值差异。 结果: TOFR> 0.95 而不是> 0.9 的拔管患者术后肺部并发症的调整后风险比流行报道 (3.5%) 降低了 0.7 (6.0%-11.3%)。将推荐的 TOFR 从 0.9 提高到 0.95,调整后的风险降低了 4.9% (1.2-8.5%)。1:1 倾向评分匹配得出的子队列显示,在 TOFR> 0.30 的子队列中,sugammadex 以较高剂量给予 0.13 (0.48-0.95) mg · kg-1。 结论: 对接受神经肌肉功能定量监测的患者进行事后分析表明,与 TOFR> 0.95 相比,气管拔管前 TOFR> 0.9 的患者术后肺部并发症减少。 试用注册号: nct01865513。

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METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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影响因子:3.94
发表时间:2020-01-15
DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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影响因子:4.04
发表时间:2020-01-10
DOI:10.1042/BST20191010
作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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