Dual antiplatelet management in the perioperative period: updated and expanded systematic review.

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies' association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

Visual and circadian regulation of Drosophila BDBT and BDBT effects on DBT and PER localization.

BRIDE OF DOUBLETIME (BDBT) interacts with the circadian kinase DOUBLETIME (DBT) and accumulates in eye foci during the dark of a light:dark cycle. BDBT foci are shown here to be broadly expressed in constant dark and low in constant light. Analysis of circadian photoreceptor cry and visual photoreceptor ninaE mutants showed that disappearance of eye BDBT foci requires both the CRYPTOCHROME and the RHODOPSIN-1 pathways. The arr1 and arr2 mutants, which affect rhodopsin quenching, eliminated BDBT foci under dark conditions. arr1 and arr2 mutants also caused increased nuclear PER protein. The changes in BDBT foci do not result from altered BDBT levels in the eye but from changes in its immunodetection. Knockdown of BDBT specifically in the eye produced constitutively nuclear PER and constitutively cytosolic DBT. The results show that BDBT is necessary for co-transport of DBT and PER into the nucleus and suggest that this process is regulated by a light-dependent mechanism.

Relation of Venous Thromboembolism Risk to Ischemic Stroke Risk in Hospitalized Patients with Cancer.

Patients with cancer are at increased risk for venous thromboembolism (VTE). However, the relationship of cancer type to the risk of arterial thrombosis in patients with high VTE risk has not been described. The goal of this study is to determine the rate of arterial thrombosis in patients with different types of solid tumors stratified by VTE risk. Using the 2012 National Inpatient Sample, we identified 373,789 hospitalizations involving patients ≥18 years associated with solid tumors, stratified by type. Data were collected on clinical characteristics, VTE (deep vein thrombosis [DVT] and pulmonary embolism [PE]), and arterial thrombosis (primary diagnosis of myocardial infarction [MI] and ischemic stroke). Subjects with solid tumors (stages I to IV) were stratified by VTE risk - high versus low. Certain solid tumor types (esophageal, lung, melanoma, ovarian, pancreatic, stomach, and uterine) were found to be associated with a higher rate of VTE compared with other cancer types (6.8% vs 3.9%, p < 0.001). Multivariate analysis applied to the high VTE risk group showed no increased risk for MI (odds ratio [OR] 0.93, p = 0.74), however, the rate of ischemic stroke was increased (OR 1.22, p < 0.001). Those in the high VTE risk group who had metastatic disease were at higher risk for arterial thrombosis (MI OR 1.35, p < 0.001, ischemic stroke OR 2.43, p < 0.001). In conclusion, different cancer types are associated with increased risk of both venous and arterial thrombosis and the risk is further increased by the presence of metastatic disease.