Reversal and removal of oral antithrombotic drugs in patients with active or perceived imminent bleeding.

Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.

Rationale and design of the safe and timely antithrombotic removal - ticagrelor (STAR-T) trial: A prospective, multi-center, double-blind, randomized controlled trial evaluating reductions in postoperative bleeding with intraoperative removal of ticagrelor by the drugsorb™-ATR device in patients undergoing cardiothoracic surgery within 48 hours from last ticagrelor dose.

BACKGROUND: Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose. METHODS: Subjects will be randomized 1:1 to receive either the DrugSorb-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24 hours chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation. CONCLUSIONS: The results from STAR-T, if positive, will potentially support FDA market approval for DrugSorb-ATR, and provide a solution to an important unmet clinical need.

Continuous glucose monitoring to assess glucose variability in type 3c diabetes.

AIM: The effectiveness of continuous glucose monitoring (CGM) in maintaining glycaemic control in type 1 diabetes mellitus and type 2 diabetes mellitus has been well demonstrated. However, the degree of glycaemic variability (GV) in people with type 3c diabetes mellitus has not been fully explored using CGM. This study aims to evaluate GV in type 3c diabetes mellitus participants and compare it to type 1 diabetes mellitus and type 2 diabetes mellitus. METHODS: Participants were grouped according to type of diabetes. GV, defined as percentage coefficient of variation (%CV), and other glycaemic indices were obtained using CGM (FreeStyle Libre, Abbott, Australia) from 82 participants across all three cohorts over a 14-day period. Comparison of baseline characteristics and GV were performed across all groups. Correlation of GV with C-peptide values, and whether pancreatic supplementation had an effect on GV were also assessed in the type 3c diabetes mellitus cohort. RESULTS: GV of type 3c diabetes mellitus participants was within the recommended target of less than %CV 36% (p = 0.004). Type 3c diabetes mellitus participants had the lowest GV among the three groups (p = 0.001). There was a trend for lower C-peptide levels to be associated with higher GV in type 3c diabetes mellitus participants (p = 0.22). Pancreatic enzyme supplementation in type 3c diabetes mellitus participants did not have an effect on GV (p = 0.664). CONCLUSIONS: Although type 3c diabetes mellitus participants were the least variable, they had the highest mean glucose levels and estimated HbA1c , which suggests that the concept of 'brittle' diabetes in type 3c diabetes mellitus is not supported by the results of CGM in this study and may be leading to poorer glycaemic control.

Long term survival after multiple microwave ablations for colorectal cancer lung metastases: A case report.

Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality in the world, with lower survival rates when metastases are present. We present a case of a 69-year-old man, diagnosed with metastatic rectal cancer to the lungs in 2015. Over the course of 5 years, he was treated with 4 microwave ablation procedures to both his lungs. Despite this, he does not have any local recurrence or any symptoms since he was first diagnosed 7 years ago. This case highlights the potential for microwave ablation to be used for curative intent in pulmonary metastases in colorectal cancer as an alternative to more invasive and complex procedures such as metastasectomies or lung resection, as well as the benefit of using microwave ablation for disease control to improve patients' quality of life.