The Canadian WATCHMAN Registry for Percutaneous Left Atrial Appendage Closure.

Background: Access to left atrial appendage closure (LAAC) in Canada is limited, due to funding restrictions. This work aimed to assess Canadian clinical practice on patient selection, postprocedural antithrombotic therapy, and safety and/or efficacy with WATCHMAN device implantation. Methods: Seven Canadian centres implanting the WATCHMAN device participated in this prospective multicentre, observational registry. All procedures were done under general anesthesia with transesophageal echocardiography guidance. Patients were prospectively followed for 2years. The long-term stroke rate was compared with the expected rate based on the CHA2DS2-VASc score. Results: A total of 272 patients who underwent LAAC with the WATCHMAN device between December 2013 and August 2019 (mean age: 75.4 years [standard deviation {SD}: 8.75]; male, 63.2%; CHA2DS2-VASc score: 4.35 [SD: 1.64]; HAS-BLED score: 3.55 [SD: 0.94]) were included. Most patients (90.4%) had prior history of bleeding (major, 80.5%; minor, 21.7%). The WATCHMAN device was successfully implanted in 269 patients (98.9%), with a few procedure-related complications, including 5 pericardial effusions requiring drainage (1.8%), and 1 death (0.4%; 22 days post-LAAC from respiratory failure). Post-LAAC antithrombotic therapy included dual antiplatelet therapy in 70.6%, single antiplatelet therapy in 18.4%, and oral anticoagulation in 13.6%. During the follow-up period (mean: 709.7 days [SD: 467.2]), an 81.4% reduction of the ischemic stroke rate occurred, based on the expected rate from the CHA2DS2-VASc score (6.0% expected vs 1.1% observed). Device-related thrombus was detected in 1.8%. Conclusions: The majority of Canadian patients who underwent LAAC had oral anticoagulation contraindication due to prior bleeding, and most were safely treated with antiplatelet therapy post-LAAC, with a low device-related thrombus incidence. Long-term follow-up demonstrated that LAAC achieved a significant reduction in ischemic stroke rate.

Contexte: Au Canada, l'accès à la fermeture de l'appendice auriculaire gauche (FAAG) est limité en raison de restrictions quant au financement de cette intervention. Le présent rapport visait à évaluer les pratiques cliniques canadiennes sur la sélection des patients, le traitement antithrombotique après l'intervention et l'innocuité ou l'efficacité par l'implantation d'un dispositif WATCHMAN. Méthodologie: Sept centres canadiens procédant à l'implantation du dispositif WATCHMAN ont participé à ce registre observationnel, prospectif et multicentrique. Toutes les interventions ont été réalisées sous anesthésie générale avec guidage par échocardiographie transœsophagienne. Les patients ont par la suite été suivis de manière prospective pendant deux ans. Le taux d'AVC à long terme a été comparé au taux attendu, selon le score CHA2DS2-VASc. Résultats: Ont été inclus à l'étude 272 patients ayant subi une FAAG avec implantation d'un dispositif WATCHMAN entre décembre 2013 et août 2019 (âge moyen : 75,4 ans [écart-type {É.-T.} : 8,75]; hommes : 63,2 %; score CHA2DS2-VASc : 4,35 [É.-T. : 1,64]; score HAS-BLED : 3,55 [É.-T. : 0,94]). La plupart des patients (90,4 %) avaient des antécédents de saignements (majeurs : 80,5 %; mineurs : 21,7 %). Le dispositif WATCHMAN a bien été implanté chez 269 patients (98,9 %), avec quelques complications associées à l'intervention, dont cinq effusions péricardiques nécessitant un drainage (1,8 %) et un décès (0,4 %; 22 jours après la FAAG, en raison d'une insuffisance respiratoire). Le traitement antithrombotique après la FAAG comprenait une bithérapie antiplaquettaire dans 70,6 % des cas, une monothérapie antiplaquettaire dans 18,4 % des cas et une anticoagulothérapie orale dans 13,6 % des cas. Pendant la période de suivi (durée moyenne : 709,7 jours [É.-T. : 467,2]), on a noté une réduction de 81,4 % du taux d'AVC ischémique observé par rapport au taux attendu selon le score CHA2DS2-VASc (taux attendu : 6,0 %; taux observé : 1,1 %). Un thrombus associé au dispositif a été détecté dans 1,8 % des cas. Conclusions: La majorité des patients canadiens qui ont subi une FAAG présentaient des contre-indications à l'anticoagulothérapie orale en raison de leurs antécédents de saignements, et la plupart ont été traités de manière sécuritaire par des thérapies antiplaquettaires après la chirurgie, avec un faible taux d'incidence de thrombus associé au dispositif. Le suivi à long terme a montré que la FAAG permet d'obtenir une réduction importante du taux d'AVC ischémique.

Safety and Feasibility of Same-Day Discharge After Left Atrial Appendage Closure.

Subacute or late complications > 24 hours after left atrial appendage closure (LAAC) are infrequent. We therefore created a clinical pathway to enable safe same-day discharge (SDD) after LAAC. Patients were assessed for overall physical conditioning, lack of significant frailty and comorbidities limiting physical abilities, good home support, and patient preference. Of 78 LAACs performed, 24 patients (30.8%) were discharged the same day: 21 were transesophageal echocardiography guided and 3 intracardiac echocardiography guided. SDD clinical pathway patients were discharged 395.4 ± 56.6 minutes after leaving the procedural room. There were no clinical complications at 1 month or in long-term follow-up. SDD is safe and feasible after LAAC, following a dedicated clinical pathway and surveillance in carefully selected patients.

DNA methylation profiles provide a viable index for porcine pluripotent stem cells.

Porcine induced pluripotent stem cells (iPSCs) provide useful information for translational research. The quality of iPSCs can be assessed by their ability to differentiate into various cell types after chimera formation. However, analysis of chimera formation in pigs is a labor-intensive and costly process, necessitating a simple evaluation method for porcine iPSCs. Our previous study identified mouse embryonic stem cell (ESC)-specific hypomethylated loci (EShypo-T-DMRs), and, in this study, 36 genes selected from these were used to evaluate porcine iPSC lines. Based on the methylation profiles of the 36 genes, the iPSC line, Porco Rosso-4, was found closest to mouse pluripotent stem cells among 5 porcine iPSCs. Moreover, Porco Rosso-4 more efficiently contributed to the inner cell mass (ICM) of blastocysts than the iPSC line showing the lowest reprogramming of the 36 genes (Porco Rosso-622-14), indicating that the DNA methylation profile correlates with efficiency of ICM contribution. Furthermore, factors known to enhance iPSC quality (serum-free medium with PD0325901 and CHIR99021) improved the methylation status at the 36 genes. Thus, the DNA methylation profile of these 36 genes is a viable index for evaluation of porcine iPSCs.

[Combination chemotherapy of paclitaxel followed by nedaplatin for human ovarian cancer].

The antitumor activity of a combination of paclitaxel (TXL) followed by nedaplatin (NDP) against SK-OV-3 human ovarian cancer was evaluated. We also compared the antitumor activity of TXL plus NDP with that of TXL plus carboplatin (CBDCA) or TXL plus cisplatin (CDDP). TXL was injected i.v. daily for four days and either NDP, CBDCA or CDDP was injected i.v. once after the TXL treatment, into tumor-bearing mice. The sequential administration of TXL prior to NDP resulted in enhanced inhibition of tumor growth in comparison with either TXL or NDP monotherapy. The combination in TXL plus NDP was synergistic and superior to that of TXL plus CDDP or TXL plus CBDCA therapy. Histological tests demonstrated that the fraction of BrdU-incorporated cells in tumor tissue was significantly inhibited by the combination of TXL with NDP. These results demonstrated the antitumor efficacy of TXL with NDP against human ovarian cancer and suggest the clinical effectiveness of combination of TXL with NDP.

A significant enhancement of therapeutic effect against hepatic metastases of M5076 in mice by a liposomal interleukin-2 (mixture).

Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small hydrophobic liposomes under optimal conditions (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 improved the distribution of IL-2 after intravenous administration as reported, previously. Liposomal IL-2 (300-10000 JRU/mouse per day) was significantly more effective than free IL-2 alone for inhibiting against the experimental metastases of M5076 in mice. The inhibitory effect of liposomal IL-2 was greatest in the liver. The ED(50) of liposomal IL-2 and that of free IL-2 in the liver were 1640 and 12500 JRU/mouse per day, respectively. This simple preparation (mixture) using IL-2 and liposome suspension is expected to have potential for increasing therapeutic efficacy against hepatic metastases.