Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Effectiveness and safety of short-term anticoagulant regimens after left atrial appendage occlusion: A systematic review and meta-analysis.

INTRODUCTION: Left atrial appendage occlusion (LAAO) provides an alternative for poor candidates of long-term oral anticoagulant (OAC) therapy; however, anticoagulant therapy after surgical procedures has limited use due to associated uncertainties. We aimed to evaluate the effectiveness and safety of the short-term use of direct oral anticoagulant (DOAC) and warfarin after LAAO. METHOD: Electronic databases such as PubMed, Embase, Medline, and Cochrane Library databases were searched up to November 11, 2022. Our study compared DOAC therapy and warfarin in patients after LAAO. A meta-analysis was conducted with the Review Manager software (version 5.4). RESULTS: The meta-analysis included 13 cohort studies with a total of 32,607 patients. Our findings indicated that the incidence of stroke/TIA/SE, peri-device leaks>5 mm, device-related thrombosis, and all-cause mortality were not significantly different between the two groups after LAAO (P > 0.05). The DOAC group had a significantly lower incidence of major bleeding (OR = 0.83, 95 % CI: 0.74-0.94, P = 0.003), any bleeding (OR = 0.34, 95 % CI: 0.23-0.51, P < 0.001), stroke/TIA/SE and major bleeding (OR = 0.57, 95 % CI: 0.34-0.95, P = 0.03), and any major adverse event (OR = 0.89, 95 % CI:0.82-0.97, P = 0.010) than the warfarin group. The subgroup analysis revealed that the rate of stroke/TIA/SE was similar in the two groups in terms of the different regions, follow-up time, study type, anticoagulant strategy, and bleeding risk. The incidence of major bleeding in the DOAC group was significantly lower than that in the warfarin group in North America, as well as at follow-up period ≤6 months, retrospective cohort, HAS-BLED average score ≥ 3. In addition, the risk of major bleeding was higher with the combination of OAC and single antiplatelet therapy (SAPT) than with OAC alone. Finally, in the North American region, retrospective cohort, and HAS-BLED average score ≥ 3, the incidence of any serious adverse event in the DOAC group was still significantly lower than that in the warfarin group. CONCLUSION: Compared to warfarin, DOAC reduced the risk of major bleeding and any serious adverse event in patients after LAAO. This advantage was particularly notable in North America and high-risk populations for bleeding. In addition, the incidence of device-related thrombosis, peri-device leaks, stroke/TIA/SE and all-cause mortality were similar in both groups. The risk of major bleeding was lower in patients taking OAC alone compared with those taking OAC plus SAPT, without increasing the risk of thrombosis.

Efficacy and safety of anticoagulation in atrial fibrillation patients with intracranial hemorrhage: A systematic review and meta-analysis.

Background: The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. Methods: PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. Results: We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. Conclusion: After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.

ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

WHAT IS KNOWN AND OBJECTIVE: Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ). METHODS: After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient. RESULTS AND DISCUSSION: The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001). WHAT IS NEW AND CONCLUSION: In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.

Benzochloroporphyrin derivative induced cytotoxicity and inhibition of tumor recurrence during photodynamic therapy for osteosarcoma.

Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dose- dependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.