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.     

Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta‐analysis

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one‐third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random‐effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23–2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.     

Peak bone mass of Iranian population: the Iranian Multicenter Osteoporosis Study.

Osteoporosis is a major public health problem in the Western countries and is projected to have a similar impact in the Middle East. It has been suggested that peak bone mineral density (BMD), a major determinant of osteoporotic fractures later in life, may be lower in this part of the world compared with the Western world. The purpose of the Iranian Multicenter Osteoporosis Study was to determine peak bone mass in a randomly chosen sample of healthy Iranian subjects. A total of 5201 participants (2340 males, mean age 42.7+/-13.8) were recruited based on randomized clustered sampling from all regions of five major cities across the country. In women, peak lumbar BMD (1.182+/-0.127 g/cm2) occurred in the 29- to 33-yr age group, whereas peak total femur BMD (1.006+/-0.126 g/cm2) occurred in the 32- to 36-yr age group. In men, peak lumbar BMD (1.181+/-0.153 g/cm2) and femoral BMD (1.096+/-0.159 g/cm2) both occurred in the 20- to 24-yr age group. When standardized to mg/cm2 units using established formulas, Iranian peak bone mass values are comparable with that of Western countries and are generally higher than that of Eastern Asian and Middle Eastern countries.     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Coronary stenting for coronary artery narrowing in a heart transplant recipient

Transplant atherosclerotic coronary disease remains the leading cause of death in heart transplant recipients. We report the first case of coronary stent implantation in a heart graft for epicardial focal stenosis. Due to the lower rate of restenosis after stenting in the native coronary artery, we suggest that coronary stenting be considered an acceptable, first intention therapeutic option instead of angioplasty alone whenever possible.     

Final score in laparoscopic cholecystectomy

Background: The role of intraoperative fluorocholangiography (IOC) in laparoscopic cholecystectomy (LC) is controversial. We evaluated the use of IOC at an institution where the study is performed routinely. Methods: Records of all patients undergoing LC during a 3-year period ending January 1, 1996 were reviewed. Results: A total of 1207 patients received IOC, whereas 116 patients did not. IOC findings were categorized as follows: normal, 1016 cases (84%); CBD stone, 149 cases (12.3%); anomalies, 23 cases (1.9%); duodenal diverticula, 10 cases (0.8%); ductal strictures, four cases (0.3%); and CBD diverticula, 5 cases (0.4%). In the 116 patients who did not receive IOC, 35 of the procedures could not be performed, whereas 81 were not attempted. Of the 149 IOC that showed CBD stones, two were false positives. Anomalies included accessory right hepatic ducts (11 cases), cystic ducts joining the right hepatic duct (seven cases), and abnormal cystic duct entries (five cases). Duct injuries occurred in 5 cases (0.4%), three before and two after IOC. Four injuries were minor; IOC prevented CBD transection. Conclusions: Routine IOC is feasible, safe, accurate, and provides critical information of immediate use during LC. By treating ductal stones at operation and identifying patients without CBD stones, IOC minimizes need for postoperative studies, including endoscopic retrograde cholangiography (ERC).     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.