BACKGROUND & AIMS Foxl1+ hepatic progenitor cells (HPCs) differentiate into cholangiocytes and hepatocytes following liver injury. We investigated the requirement for Foxl1+ HPCs in recovery from liver injury in mice. METHODS We developed mice in which we can trace and delete Foxl1-expressing HPCs and their descendants (Foxl1-Cre;RosaYFP/iDTR mice). Foxl1-Cre-negative mice were used as controls. Liver damage was induced in male mice by placing them on choline-deficient, ethionine-supplemented (CDE) diets for 15 days; mice were then placed on normal diets and allowed to recover. Liver damage was induced in female mice by placing them on 5-diethoxycarbonyl-1,4-dihydrocollidine-containing diets, followed by a recovery period. Some mice were given injections of diphtheria toxin mice during the recovery phase, to delete Foxl1-Cre–marked HPCs and their descendants. Livers were collected from all mice and analyzed by immunofluorescence, quantitative reverse transcription PCR, flow cytometry, and histologic analyses. RESULTS Foxl1-Cre-marked HPCs were required for development of cholangioctyes and hepatocytes in livers following CDE diet-induced injury. A smaller percentage of YFP+ hepatocytes contained markers of oxidative stress, DNA damage, or cell death than YFP-negative hepatocytes, indicating that YFP+ hepatocytes are newly formed cells. Injection of diphtheria toxin deleted YFP+ cells from Foxl1-Cre;RosaYFP/iDTR mice and prevented the resolution of hepatic steatosis. In mice recovering from dihydrocollidine-containing diet-induced injury, most cholangiocytes arose from Foxl1-Cre-marked HPCs. Deletion of YFP+ cells did not alter levels of markers of liver injury or liver function. CONCLUSIONS Based on studies of Foxl1-Cre;RosaYFP/iDTR mice, Foxl1+ HPCs and/or their descendants are required for development of cholangioctyes and hepatocytes in liver following CDE diet-induced injury.

Introduction High‐power short‐duration (HPSD) ablation is a novel strategy using contact force‐sensing catheters optimized for power‐controlled radiofrequency ablation for atrial fibrillation (AF). This study investigates the outcomes of HPSD (50 W delivered for up to 15 s, Lesion Size Index of 5–6) compared to standard‐power standard‐duration (SPSD) (20–25 W until 400–500 gram seconds, up to 60 s) and temperature‐controlled noncontact (TCNC) (20‐40 W up to 60 s of ablation) settings. Methods We studied consecutive cases of patients with AF undergoing pulmonary vein isolation with TCNC, SPSD, and HPSD between January 7th, 2013 and January 11th, 2019. Procedural data collected include time to isolate the left (LPVT) and right pulmonary veins (RPVT), total ablation time (TAT), and radiofrequency ablation delivery time (RADT). Clinical data collected include sinus rhythm maintenance postprocedure. Results One hundred and seventy‐one patients were studied (44 TCNC, 51 SPSD, 76 HPSD). RADT was shorter when comparing HPSD to SPSD (25 vs. 41 min; p < .01), HPSD to TCNC (25 vs. 76 min; p < .01), and SPSD to TCNC groups (41 vs. 76 min; p < .01). TAT, LPVT, and RPVT were reduced between HPSD versus SPSD, HPSD versus TCNC, and SPSD versus TCNC groups, respectively (p < .01). There was no difference in sinus rhythm maintenance by Kaplan–Meier survival analysis (log rank test p = .12), after 3 or 12 months between groups overall, and when stratified by AF type, left atrial volume, CHA2DS2‐VASc score, or left ventricular ejection fraction. Conclusion AF ablation with HPSD reduced procedure times with similar sinus rhythm maintenance compared to SPSD and TCNC.

Introduction High-power short-duration (HPSD) ablation is a novel strategy using contact force-sensing catheters optimized for radiofrequency ablation for atrial fibrillation (AF). No study has directly compared HPSD versus standard-power standard-duration (SPSD) contact force-sensing settings in patients presenting for repeat ablation with AF recurrence after initial ablation. Methods We studied consecutive cases of patients with AF undergoing repeat ablation with SPSD or HPSD settings after their initial pulmonary vein isolation (PVI) with temperature controlled non-contact force, SPSD or HPSD settings between 6/23/14 and 3/4/20. Procedural data collected included radiofrequency ablation delivery time (RADT). Clinical data collected include sinus rhythm maintenance post-procedure. Results A total of 61 patients underwent repeat ablation (36 SPSD, 25 HPSD). A total of 51 patients (83.6%) were found to have pulmonary vein reconnections necessitating repeat isolation, 10 patients (16.4%) had durable PVI and ablation targeted non-PV sources. RADT was shorter when comparing repeat ablation using HPSD compared to SPSD (22 vs 35 min; p = 0.01). There was no difference in sinus rhythm maintenance by Kaplan–Meier survival analysis (log rank test p = 0.87), after 3 or 12-months between groups overall, and when stratified by AF type, left atrial volume index, CHA2DS2-VASc score, or left ventricular ejection fraction. Conclusion We demonstrated that repeat AF ablation with HPSD reduced procedure times with similar sinus rhythm maintenance compared to SPSD in those presenting for repeat ablation.

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