Shadrin, Ilya Y.

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative cardiomyopathy characterized by myocardial granulomatous inflammation, leading to conduction system abnormalities and ventricular arrhythmias. Cardiac resynchronization therapy (CRT) outcomes in CS patients are controversial. The efficacy of CRT with left bundle branch area pacing (LBBAP) in these patients has not yet been elucidated. Objective To evaluate electrocardiographic, echocardiographic and long-term clinical outcomes after CRT with LBBAP in CS patients. Methods In this retrospective multicenter study, conducted between June 2020 and March 2024, patients with a histopathologically confirmed diagnosis of CS with an indication for CRT were included in the analysis. The primary outcome was a composite of all-cause mortality, heart failure related hospitalizations, implantable cardioverter defibrillator shocks and requirement of left ventricular assist device/heart transplant. The primary safety outcome was procedure-related complications. Secondary outcomes included pre- and post-procedural electrocardiographic and echocardiographic parameters and change in NYHA functional class. Results A total of 16 patients were included in the analysis (mean age 66.2 ± 9.4 years; 62.5% female; body mass index 30.4 ± 8.5 kg/m2). Four patients (25%) had isolated CS. The median follow-up was 579 [Q1: 295.5 – Q3: 797.5] days. Five patients (31.25%) experienced the composite outcome. Among these, two patients (12.5%) had acute heart failure related hospitalizations, two patients (12.5%) died due to severe pulmonary hypertension and sepsis complicated by cardiorenal syndrome, respectively; and one patient (6.25%) presented an episode of ventricular tachycardia that was successfully terminated with an implantable cardioverter defibrillator shock. No patients required advanced heart failure therapies. There were no procedure-related complications. There was a significant improvement in paced QRS duration (Pre 156.8 ± 36.2 vs. Post 128.3 ± 22.3 milliseconds, p=0.003), left ventricular ejection fraction (Pre 36.5 ± 10.6% vs. Post 50.4 ± 12.2%, p<0.001), left ventricular end systolic diameter (Pre 52 [39.5 – 84.3] vs. Post 41 [29 – 72] millimeters, p=0.011) and left ventricular end diastolic diameter (Pre 66.7 [48 – 159] vs. Post 61 [44 – 135] millimeters, p=0.023). Ten (62.5%) patients exhibited an improvement ≥ I in NYHA functional class post procedure. Conclusion In CS patients, CRT with LBBAP was associated with significant improvements in electrocardiographic and echocardiographic parameters, as well as NYHA functional class, alongside favorable long-term clinical outcomes by optimizing interventricular dyssynchrony.Graphical abstract ECG and Echo parameters

Objective The aim of the study was to compare vaginal wound healing after exosome injection in a porcine mesh exposure model with (1) single versus multiple dose regimens and (2) acute versus subacute exposure. Methods Six 80-kg Yorkshire-crossed swine each had 2 polypropylene meshes implanted to create the vaginal mesh exposure model. Animals were divided into 3 groups based on number and timing of exosome injection: (1) single purified exosome product (PEP) injection (acute-single), (2) weekly PEP injections (acute-weekly, 4 total injections), and (3) delayed single injection (subacute-single). Acute and subacute injections occurred 1 and 8 weeks after mesh implantation, respectively. EdU, a thymidine analog, was given twice weekly after the first injection to track tissue regeneration. Euthanasia and tissue analysis occurred 4 weeks after the first injection. ImageJ was used to quantify epithelial thickness, cellular proliferation, and capillary density. Statistical analysis was performed using analysis of variance and post hoc Tukey test. Results Acute-single PEP injection tissues mirrored pilot study results, validating replication of protocol. Within the acute groups, weekly dosing resulted in 1.5× higher epithelial thickness (nonsignificant), 1.8× higher epithelial proliferation ( P < 0.05), and 1.5× higher regenerated capillary density ( P < 0.05) compared with single injection. Regarding chronicity of the exposure, the subacute group showed 1.7× higher epithelial proliferation (nonsignificant) and similar capillary density and epithelial thickness as compared with the acute group. Conclusions Exosome redosing resulted in significantly greater epithelial proliferation with significantly higher regenerated capillary density, leading to a trend toward thicker epithelium. Subacute exposure exhibited similar regeneration to acute exposure despite a delayed injection timeline. These results contribute to a growing body of preclinical research demonstrating utility of exosomes in pelvic floor disorders.

Objectives The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure. Methods Sixteen polypropylene meshes (1×1–3×3 cm) were implanted in the vaginas of 7 Yorkshire-crossed pigs by urogynecologic surgeons (day 0). On day 7, group 1 underwent surgical intervention via vaginal tissue suture reclosure with (n=2 pigs, n=4 meshes) or without (n=2 pigs, n=4 meshes) exosome injection; group 2 underwent medical intervention with an exosome injection (n=3, n=8 meshes). One animal in group 2 was given oral 2′-deoxy-5-ethynyluridine to track cellular regeneration. Euthansia occurred at 5 weeks. Results Mesh exposures treated with surgical closure alone experienced reexposure of the mesh. Exosome treatment with or without surgical closure resulted in partial to full mesh exposure resolution up to 3×3 cm. Exosome-treated tissues had significantly thicker regenerated epithelial tissue (208 μm exosomes-only and 217 μm surgery+exosomes, versus 80 μm for surgery-only; P < 0.05); evaluation of 2′-deoxy-5-ethynyluridine confirmed de novo regeneration throughout the epithelium and underlying tissues. Capillary density was significantly higher in the surgery+exosomes group ( P = 0.03). Surgery-only tissues had a higher inflammatory and fibrosis response as compared with exosome-treated tissues. Conclusions In this pilot study, exosome treatment augmented healing in the setting of vaginal mesh exposure, reducing the incidence of mesh reexposure after suture closure and decreasing the area of mesh exposure through de novo tissue regeneration after exosome injection only. Further study of varied local tissue conditions and mesh configurations is warranted.

In patients with advanced heart failure (HF), temporary mechanical circulator support (TMCS) is used to improve hemodynamics, via left ventricular unloading, and end-organ function as a bridge to definitive therapy. While listed for cardiac transplantation, use of TMCS may be prolonged, preventing adequate mobility. Here, we describe the technique for placement of a percutaneous axillary intra-aortic balloon pump (IABP) using single-site arterial access to facilitate ambulation and subsequent safe removal without surgery or a closure device. Retrospective review of the experience with this approach at a single institution between September 2017 and February 2020 documented feasibility and safety. Baseline demographics, hemodynamic data, and clinical outcomes were collected. Thirty-eight patients had a total of 56 IABPs placed. There were no significant access site or cerebrovascular complications. One fifth of IABPs (21.4%) had balloon failure or migration, requiring placement of a new device, though no patients had significant complications from balloon failure. The majority (81.6%) of patients in the cohort on axillary IABP support were ambulatory and ultimately received the intended therapy (63.2% transplant, 13.2% durable left ventricular assist device, 5.3% other cardiac surgery). Percutaneous, axillary IABP is feasible and associated with an acceptable complication rate as a bridge to definitive therapy.