Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

椎体强化的生物力学回顾(上)

介绍：骨质疏松的椎体其强度和刚度都会降低，这就意味着椎体的破坏负荷与抵抗压缩变形的能力均降低。强度和刚度的降低量与骨质疏松的严重程度呈正比。因为这些特性与骨小梁的密度有很大的相关性。椎体压缩性骨折后强度和刚度值与骨折前相比进一步降低。其临床结果是：（1）骨质疏松导致椎体强度降低，继而导致最初的骨质疏松性骨折，骨折后的椎体有进一步压缩性骨折的倾向。[第一段]     

Morphologic Analysis of the Carpal Tunnel and Median Nerve Following Open and Endoscopic Carpal Tunnel Release

Background: Endoscopic carpal tunnel release (ECTR) has purported advantages over open release such as reduced intraoperative dissection and trauma and more rapid recovery. Endoscopic carpal tunnel release has been shown to have comparable outcomes to open release, but open release is considered easier and safer to perform. Previous studies have demonstrated an increase in carpal tunnel volume, regardless of the technique used. However, the mechanism by which this volumetric increase occurs has been debated. Our study will determine through magnetic resonance imaging (MRI) analysis the morphologic changes that occur in both open carpal tunnel release (OCTR) and ECTR, thereby clarifying any morphologic differences that occur as a result of the 2 operative techniques. We hypothesize that there will be no morphologic differences between the 2 techniques. Methods: This was a prospective study to compare the postoperative anatomy of both techniques with MRI. Nineteen patients with clinical and nerve conduction study–confirmed carpal tunnel syndrome underwent either open or endoscopic release. Magnetic resonance imaging was performed preoperatively and 6 months postoperatively in all patients to examine the volume of the carpal tunnel, transverse distance, anteroposterior (AP) distance, divergence of tendons, and Guyon’s canal transverse and AP distance. Results: There was no significant difference in the postoperative morphology of the carpal tunnel and median nerve between OCTR and ECTR at 6-month follow-up on MRI. Conclusion: We conclude that there are no morphologic differences in OCTR and ECTR. It is an increase in the AP dimension that appears to be responsible for the increase in the volume of the carpal tunnel.     

Complete nucleotide sequence of a begomovirus associated with satellites molecules infecting a new host Tagetes patula in India

In the year 2012 leaf curl disease was observed on Marigold (Tagetes patula) in Lakshmangrh, Sikar province of India. Affected plants were severely stunted with apical leaf curl and crinkled leaves, symptoms typical of begomovirus infection. This is the first report of complete nucleotide sequence of a begomovirus associated with satellites molecules infecting a new host Tagetes patula in India.