The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

端粒长度与认知障碍及其中药治疗的研究现况

认知障碍是指记忆、语言、理解和判断等一个或多个方面的功能障碍,包括轻度认知障碍和各种类型的痴呆症。痴呆症是认知障碍最严重的表现,是一种导致患者日常生活、社会交往和工作能力发生显著变化的综合征。阿尔茨海默病(AD)是最常见的痴呆症类型,其次是血管性痴呆(VD)和其他神经退行性痴呆[1]。已知年龄与认知功能的退化密切相关。     

Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.     

The effect of massage therapy on pain after surgery: A comprehensive meta-analysis

BackgroundFindings on the usefulness of massage therapy (MT) in postoperative pain management are often inconsistent among studies.ObjectivesThis study’s aim is to conduct a meta-analysis of randomized controlled trials (RCT) to clarify the effects of massage therapy in the treatment of postoperative pain.MethodsThree databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for RCTs published from database inception through January 26, 2021. The primary outcome was pain relief. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The random-effect model was used to calculate the effect sizes and standardized mean difference (SMD) with 95 % confidential intervals (CIs) as a summary effect. The heterogeneity test was conducted through I². Subgroup and sensitivity analyses were used to explore the source of heterogeneity. Possible publication bias was assessed using visual inspection of funnel plot asymmetry.ResultsThe analysis included 33 RCTs and showed that MT is effective in reducing postoperative pain (SMD, −1.32; 95 % CI, −2.01 to −0.63; p = 0.0002; I² = 98.67 %). A similar significant effect was found for both short (immediate assessment) and long terms (assessment performed 4–6 weeks after the MT). Remarkably, we found neither the duration per session nor the dose had an impact on the effect of MT and there seemed to be no difference in the effects of different MT types. In addition, MT seemed to be more effective for adults. Furthermore, MT had better analgesic effects on cesarean section and heart surgery than orthopedic surgery.LimitationsPublication bias is possible due to the inclusion of studies in English only. Additionally, the included studies were extremely heterogeneous. Double-blind research on MT is difficult to implement, and none of the included studies is double-blind. There was some heterogeneity and publication bias in the included studies. In addition, there is no uniform evaluation standard for the operation level of massage practitioners, which may lead to research implementation bias.ConclusionsMT is effective in reducing postoperative pain in both short and long terms.     

The fate of aortic valve after rheumatic mitral valve surgery

ObjectiveDeterioration of the native aortic valve function by a late progression of rheumatic disease is not infrequent in patients who underwent rheumatic mitral valve surgery; however, this phenomenon has not been clearly quantified.MethodsA total of 1155 consecutive patients (age 52.0 ± 12.9 years; 807 female) who underwent rheumatic mitral valve surgery without concomitant aortic valve surgery from 1997 to 2015 were enrolled. The primary end point was the composite of progression to severe aortic valve dysfunction or a requirement of subsequent aortic valve replacements during follow-up. To determine the risk factors of the primary outcome, we performed the generalized linear mixed model.ResultsThe baseline severities of aortic valve were none to trivial in 880 patients (76.2%), mild in 256 patients (22.2%), and moderate in 19 patients (1.6%). The latest 1062 echocardiographic assessments (91.9%; median, 81.2 postoperative months; interquartile range, 37.3-132.1 months) demonstrated 26 cases (0.33%/patient-year) meeting the primary end point during follow-up. Cumulative incidence of the primary end point at 10 years was 0.4% ± 0.3% and 7.4% ± 2.5% depending on the presence of mild or greater aortic valve dysfunction at baseline (P < .01). In multivariable analyses, aortic valve peak pressure gradient (odds ratio, 1.14; 95% confidence interval, 1.10-1.20), aortic regurgitation degree (mild over none: odds ratio, 3.26; 95% confidence interval, 1.15-9.23), and time (odds ratio, 1.30; 95% confidence interval 1.19-1.41) were significantly associated with the occurrence of the primary end point.ConclusionsProgression of severe aortic valve dysfunction and the need for aortic valve replacement are uncommon in patients undergoing rheumatic mitral valve surgery. However, such events were relatively common among those with mild or greater aortic valve dysfunction at the time of mitral valve surgery.     

肌萎缩侧索硬化伴认知功能障碍的研究进展

认知功能障碍在肌萎缩侧索硬化（ALS）患者中是普遍存在的，ALS伴认知功能障碍常提示预后不良。近年来对ALS患者认知功能障碍的研究取得了一定的进展，本文对ALS伴认知功能障碍的临床特点、生物标志物、遗传学特征和最新治疗进展进行综述，以期为ALS伴认知功能障碍的临床诊疗提供新思路。