Remifentanil versus Dexmedetomidine in Cardiac Surgery Patients with Noninvasive Ventilation Intolerance: Protocol for the REDNIVI Trial.

BACKGROUND: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. METHODS: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. CONCLUSIONS: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. CLINICAL TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.

BACKGROUND: The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. OBJECTIVES: This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. RESULTS: Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05). CONCLUSIONS: Serum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.

Label-free proteomic analysis of serum exosomes from paroxysmal atrial fibrillation patients.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac heterogeneous rhythm disorder. It represents a major cause of mortality and morbidity, mainly related to embolic events and heart failure. Mechanisms of AF are complex and remain incompletely understood. Recent evidence suggests exosomes are membrane-coated objects released by many cell-types. Their presence in body fluids and the variable surface composition and content render them attractive as a mechanism for potential biomarkers. However, the content of serum exosomes of AF patients has not been fully delineated. METHODS: In this work, the serum exosomes from AF patients and healthy donors were used to compare changes in the exosome protein content. Exosomes were isolated from serum of AF patients and healthy donors and their purity was confirmed by Western blotting assays and transmission electron microscopy (TEM). Label-free LC-MS/MS quantitative proteomic analysis was applied to analyze protein content of serum exosomes. RESULTS: A total of 440 exosomal protein groups were identified, differentially expressed proteins were filtrated with fold change ≥ 2.0 (AF/controls protein abundance ratio ≥ 2 or ≤ 0.5) and p value less than 0.05 (p < 0.05), significantly changed in abundance group contains 39 elevated proteins and 18 reduced proteins, while consistent presence/absence expression profile group contains 40 elevated proteins and 75 reduced proteins. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the anticoagulation, complement system and protein folding. Parallel-Reaction Monitoring Relative Quantitative Analysis (PRM) further suggested that AF related to complement system and protein folding. CONCLUSIONS: These results revealed the composition and potential function of AF serum exosomes, thus providing a new perspective on the complement system and protein folding to AF.

Outcome of non-vitamin K oral anticoagulants in the treatment of left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

BACKGROUND: Data comparing dabigatran with rivaroxaban regarding the resolution of left atrial/left atrial appendage (LA/LAA) thrombus in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to compare the efficacy and safety of dabigatran vs rivaroxaban regarding the resolution of LA/LAA thrombus in patients with nonvalvular AF. METHODS: This retrospective study enrolled nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2014 and January 2019. Altogether, 34 patients with LA/LAA thrombus detected by transesophageal echocardiography (TEE) were enrolled. Among them, 12 patients were treated with dabigatran 150 mg bid and the other 22 with rivaroxaban 20 mg qd. Follow-up TEE was performed within greater than or equal to 3 weeks to less than 6 months of the initial TEE to evaluate the resolution of the LA/LAA thrombus. RESULTS: Baseline patient characteristics were similar in the two groups. Overall, 18 patients (81.8%) in the rivaroxaban group had complete thrombus resolution after 70.3 ± 22.1 treatment days, and 10 patients (83.3%) in the dabigatran group had complete thrombus resolution after 69.3 ± 47.9 treatment days. There was no significant difference between the groups (P = .6). TEE showed that the average length, width, and area of thrombus significantly decreased in both groups after treatment, although there was no significant difference in the amount of change in these parameters between the two groups after treatment (P = .6). Undissolved thrombus in two patients in the rivaroxaban group did dissolve after switching to dabigatran. CONCLUSIONS: The results suggest that both dabigatran and rivaroxaban are potential options for treating LA/LAA thrombus in patients with nonvalvular AF. Dabigatran could be an alternative option for the resolution of LA/LAA thrombus resistant to rivaroxaban.

Strategy of catheter ablation for para-Hisian premature ventricular contractions with the assistance of remote magnetic navigation.

INTRODUCTION: Catheter ablation of frequent para-Hisian premature ventricular contractions (PH-PVCs) is considered to be challenging. The purpose of this study was to evaluate the strategy, potential technical advantages, and clinical outcomes of remote magnetic navigation (RMN) in the ablation of PH-PVCs. METHODS: Fifteen consecutive patients with PH-PVCs were included in this study. Electrical mapping was initially performed in the right ventricular septum by manipulating the RMN catheter with a "U-curve." In the case of no optimal ablation site or ablation failure, the ablation catheter was directed to the left ventricular (LV) septum through a transseptal approach for further mapping and ablation by manipulating the RMN catheter with a "reverse S-curve." RESULTS: Nine of 15 patients were submitted to ablation on the right side. However, ablation success was only achieved in only three (33%) cases. Of the other 12 patients, 11 underwent LV mapping and ablation. In this subset, 9 of 11 (82%) PH-PVCs were totally eliminated on the left side. Overall, RMN-guided mapping and ablation successfully eliminated 12 (80%) of 15 idiopathic PH-PVCs. During follow-up, the reoccurrence of PVCs was reported in 1 (8%) of 12 patients. No atrioventricular block was observed during or after the procedure. CONCLUSION: RMN-guided catheter ablation for PH-PVCs is effective and safe in unselected patients. Due to the excellent reachability and contact with special morphologies of the RMN catheter on both sides of the ventricular septum, RMN can be considered an effective approach for frequent PH-PVCs.

Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

NEW FINDINGS: What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P < 0.01). However, RDN increased the VFT by 13% (135 ± 10 versus 118 ± 7.5 ms, P < 0.05) and decreased the DFT by 27% (30 ± 6.3 versus 21.8 ± 4.7 J, P < 0.05) in the treated hearts compared with the failing hearts. Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1.48 ± 0.2 versus 1.26 ± 0.11, P < 0.05) and decreased the dispersion of ARI by 25% (0.08 ± 0.02 versus 0.06 ± 0.01, P < 0.01) in the treated group compared with the HF group. The findings of this study suggest that RDN can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action on VF in a canine model of pacing-induced HF.

A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2.

Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 - 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2WSBdel1) that eliminates the majority of the R2d2WSB copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2WSBdel1, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2WSBdel1, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2WSB heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2WSB transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system.

Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines.

BACKGROUND: The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF) canine hearts. METHODS: Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. RESULTS: In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. CONCLUSIONS: A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.

Cryoballoon ablation in Chinese patients with paroxysmal atrial fibrillation: 1-year follow-up.

OBJECTIVES: We assessed the effectiveness and safety of cryoballoon ablation (CBA) in the Chinese population with paroxysmal atrial fibrillation (AF) with a 1-year follow-up and determined the association of early recurrence of atrial tachyarrhythmias (ERAT) with late recurrence (LR). METHODS: A total of 114 patients (age 61 ± 10 years, 78 males) with paroxysmal AF who underwent CBA were consecutively enrolled. After procedures, patients were observed for 3 days with continuous electrocardiogram monitoring in the hospital with routine follow-up visits at 3 months, 6 months, and 1 year. Documented atrial tachyarrhythmia >30 seconds was defined as recurrence. ERAT was defined as any recurrence during the first 3 months, and LR was recurrence between 3 and 12 months. RESULTS: With the first 3 months as blanking period, 76% of patients were free of LR at 12 months. Five patients (4%) experienced complications, including phrenic nerve palsy, stroke, and groin complications. Forty-five percent of patients had ERAT in the first 3 months and 31% of patients had ERAT in the first 3 days. Patients with ERAT had higher LR rate (LRR) than those without ERAT (43% vs 8%, P < 0.001). The LRR of patients with ERAT only in the first 3 days was lower than those with ERAT both in the first 3 days and in 4-90 days (29% vs 64%, P = 0.036). CONCLUSIONS: CBA was an effective and safe treatment option for paroxysmal AF. Patients with ERAT had higher LRR after CBA of AF. The time when ERAT occurred had an impact on LRR.

Enhanced dewaterability of sewage sludge with zero-valent iron-activated persulfate oxidation system.

The potential benefits of zero-valent iron-activated persulfate (Na2S2O8) oxidation in enhanced dewaterability of sludge, along with the associated mechanisms were investigated in this study. The sludge dewaterability was evaluated in terms of specific resistance to filtration (SRF) and water content. Based on these indexes, it was observed that ZVI-S2O8(2) oxidation effectively improved sludge dewaterability. The optimal conditions to give preferable dewaterability were found when the molar ratio of ZVI/S2O8(2-) was 5:1 and pH value was 3.0. The most important mechanism was proposed to be the degradation of extracellular polymeric substances (EPS) incorporated in sludge flocs and rupture of microbial cells. Three-dimensional excitation-emission matrix fluorescence spectra revealed that the powerful SO4- and ·OH generated from ZVI-S2O8(2-) system destroyed the particular functional groups of fluorescing substances (aromatic protein-like and tryptophan protein-like substances), resulting in the release of bound water and the subsequent enhancement of dewaterability. Therefore, ZVI/S2O8(2-) oxidation is an alternative approach showing great potential to be applied in sludge treatment plants.

Niobium carbide MXenzyme-Driven comprehensive cholesterol regulation for photoacoustic image-guided and anti-inflammatory photothermal ablation in atherosclerosis.

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

Piezocatalytic Schottky Junction Treats Atherosclerosis by a Biomimetic Trojan Horse Strategy.

The atherosclerotic vulnerable plaque is characterized by the foamy macrophage burden, involving impaired cholesterol efflux and deficient efferocytosis. Correspondingly, piezocatalytic therapy is an emerging solution for eliminating the foamy macrophage burden with satisfactory spatiotemporal controllability and deep penetration depth. Herein, a biomimetic Trojan horse (Au-ZnO@MM) is engineered by coating the macrophage membrane (MM) onto the surface of a rod-like Au-ZnO Schottky Junction to effectively relieve the atherosclerotic progression. These Trojan horses with the coating of MM are actively transported into subsistent foamy macrophages and generate abundant reactive oxygen species (ROS) via ultrasound-activated piezocatalysis. ROS-initiated autophagy and mitochondrial dysfunction induce substantial cell apoptosis, alleviating the burden of subsistent foamy macrophages. The resulting apoptotic fragments further significantly facilitate cholesterol excretion and trigger efferocytosis of intraplaque fresh macrophages. Ultimately, the biomimetic Au-ZnO@MM piezocatalyst not only inhibits the foaming capacity of macrophages, but also improves the function of removing cell debris, which can stabilize atherosclerotic vulnerable plaque. Meanwhile, the plasmon resonance effect of integrated gold nanoparticles enables favorable photoacoustic molecular imaging for real-time image-guided atherosclerotic therapy. This proposed biomimetic Trojan horse strategy provides the paradigm of employing ultrasound-activated piezocatalytic methodology for enhanced atherosclerotic theranostics.

Sonosynthetic Cyanobacteria Oxygenation for Self-Enhanced Tumor-Specific Treatment.

Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well-known low penetration depth of external light. Here, ultrasound-mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound-induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof-of-concept sonosynthesis (sonoafterglow-induced photosynthesis) in cancer therapy. Chlorin e6, a typical small-molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue-penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia-inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis.

Therapeutic efficacy of ECs Foxp1 targeting Hif1α-Hk2 glycolysis signal to restrict angiogenesis.

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Identification of senescence-related genes for potential therapeutic biomarkers of atrial fibrillation by bioinformatics, human histological validation, and molecular docking.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Senescent CD8+ T cells: a novel risk factor in atrial fibrillation.

AIMS: Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms. METHODS AND RESULTS: Single-cell RNA sequencing and multicolor flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (p < 0.0001) and the left atria (p < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, p < 0.05) and postprocedural recurrence (hazard ratio = 22.955, p < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping. CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.

Soluble PILRα: A novel plasma biomarker for atrial fibrillation progression and recurrence after catheter ablation.

BACKGROUND: We aimed to identify plasma biomarkers of atrial fibrillation (AF) progression and recurrence after catheter ablation. METHODS: Using AF gene profiling data from GEO database, a weighted gene co-expression network analysis (WGCNA) was conducted to determine the most significant module and hub genes associated with AF. Subsequently, 318 consecutively admitted patients who had undergone radiofrequency catheter ablation were enrolled in this study. RESULTS: WGCNA results revealed that paired immunoglobulin-like type 2 receptor alpha (PILRA) was the only black module gene highly correlated with clinical traits. Plasma soluble PILRα (sPILRα) levels were elevated in patients with AF and significantly elevated in patients with persistent versus paroxysmal AF (4.64 ± 2.74 vs. 3.04 ± 1.56 ng/mL, p < 0.001). Elevated sPILRα level was an independent risk factor for AF progression even after adjusting for traditional factors (adjusted odds ratio: 3.06, 95 % confidence interval [CI]: 1.88-5.27, p < 0.001) and AF recurrence after catheter ablation in patients with persistent AF (adjusted hazards ratio: 4.41, 95 % CI: 1.22-15.92, p = 0.023). CONCLUSIONS: WGCNA screening of GEO microarray gene profiling data showed PILRA expression levels to be correlated with AF progression and recurrence after catheter ablation in patients with persistent AF.

[Clinical application and effectiveness of patellar tunnel locator in medial patellofemoral ligament reconstruction surgery].

Objective: To evaluate the operability and effectiveness of a self-developed patellar bone canal locator (hereinafter referred to as "locator") in the reconstruction of the medial patellofemoral ligament (MPFL). Methods: A total of 38 patients with recurrent patellar dislocation who met the selection criteria admitted between January 2022 and December 2022 were randomly divided into study group (the patellar canal was established with a locator during MPFL reconstruction) and control group (no locator was used in MPFL reconstruction), with 19 cases in each group. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, body mass index, disease duration, patella Wiberg classification, constituent ratio of cartilage injury, Caton index, tibia tubercle-trochlear groove, and preoperative Lysholm score, Kujal score, Tegner score, visual analogue scale (VAS) score, and so on. The Lysholm score, Kujal score, Tegner score, and VAS score were used to evaluate knee joint function before operation and at 3 days,1 month, 3 months, and 6 months after operation. The ideal prepatellar cortical thickness and canal length were measured before operation, and the actual prepatellar cortical thickness and canal length after operation were also measured, and D1 (the distance between the ideal entrance and the actual entrance), D2 (the ideal canal length minus the actual canal length), D3 (the ideal prepatellar cortical thickness minus the actual prepatellar cortical thickness) were calculated. Results: Patients in both groups were followed up 6-8 months (mean, 6.7 months). The incision length and intraoperative blood loss in the study group were smaller than those in the control group, but the operation time was longer than that in the control group, the differences were significant ( P<0.05). There was no complication such as incision infection, effusion, and delayed healing in both groups, and no further dislocation occurred during follow-up. One patient in the study group had persistent pain in the anserine area after operation, and the symptoms were relieved after physiotherapy. The VAS score of the two groups increased significantly at 3 days after operation, and gradually decreased with the extension of time; the change trends of Lysholm score, Kujal score, and Tegner score were opposite to VAS score. Except that the Lysholm score and Kujal score of the study group were higher than those of the control group at 3 days after operation, and the VAS score of the study group was lower than that of the control group at 3 days and 1 month after operation, the differences were significant ( P<0.05), there was no significant difference in the scores between the two groups at other time points ( P>0.05). Patellar bone canal evaluation showed that there was no significant difference in preoperative simulated ideal canal length, prepatellar cortical thickness, and postoperative actual canal length between the two groups ( P>0.05). The postoperative actual prepatellar cortical thickness of the study group was significantly smaller than that of the control group ( P<0.05). D1 and D3 in the study group were significantly higher than those in control group ( P<0.05), but there was no significant difference in D2 between the two groups ( P>0.05). Conclusion: The locator can improve the accuracy of MPFL reconstruction surgery, reduce the possibility of intraoperative damage to the articular surface of patella and postoperative patellar fractures.

Initial experience of a novel method for electrical isolation of the superior vena cava using cryoballoon in patients with atrial fibrillation.

BACKGROUND: Damage to the sinus node (SN) has been described as a potential complication of superior vena cava (SVC) isolation. There have been reports of permanent SN injury requiring pacemaker implantation during isolation of the SVC. HYPOTHESIS: It is safe and effective to isolate SVC with the second-generation 28-mm cryoballoon by using a novel method. METHODS: Forty-three patients (including six redo cases) with SVC-related atrial fibrillation (AF) from a consecutive series of 650 patients who underwent cryoballoon ablation were included. After pulmonary vein isolation was achieved, if the SVC trigger was identified, the SVC was electrically isolated using the cryoballoon. First, the cryoballoon was inflated in the right atrium (RA) and advanced towards the SVC-RA junction. After total occlusion was confirmed by dye injection with total retention of contrast in the SVC, the SVC-RA junction was determined. Next, the cryoballoon was deflated, advanced into SVC, then reinflated, and pulled back gently. The equatorial band of the cryoballoon was then set slightly (4.32 ± 0.71 mm) above the SVC-RA junction for isolation of the SVC. RESULTS: Real-time SVC potential was observed in all patients during ablation. The mean time to isolation was 24.5 ± 10.7 s. The SVC was successfully isolated in all patients. The mean number of freeze cycles was 2.5 ± 1.4 per patient, and the mean ablation time was 99.8 ± 22.7 s. A transient phrenic nerve (PN) injury occurred in one patient (2.33%). There were no SN injuries. Freedom from AF rates at 6 and 12 months was 97.7% and 93.0%, respectively. CONCLUSIONS: This novel method for SVC isolation using the cryoballoon is safe and feasible when the SVC driver during AF is determined and could avoid SN injury. PN function should still be carefully monitored during an SVC isolation procedure.

Different electrophysiological characteristics of cavo-tricuspid isthmus dependent atrial flutter guided by robotic magnetic navigation in patients with and without prior cardiac surgery.

BACKGROUD: Cavo- tricuspid isthmus dependent atrial flutter (CTI- AFL) is a common atrial arrhythmia in patients with prior cardiac surgery (postsurgical AFL) and without prior cardiac surgery (nonsurgical AFL). However, there is only limited data regarding the eletrophysiological differences between the CTI- AFL in the postsurgical patients and the nonsurgical patients. HYPOTHESIS: We aimed to investigate the differences in clinical and electrophysiological characteristics between the postsurgical group and nonsurgical group and to evaluate the acute and long-term outcomes after ablation guided by robotic magnetic navigation (RMN) in both the groups. Methods Fourty-two consecutive patients with nonsurgical AFL and 21 with postsurgical AFL were retrospectively analyzed in our center. Electrocardiographic (ECG) analysis and three-dimensional electrophysiological study were performed in all the patients. RESULTS: The results revealed that only 55.6% of postsurgical patients with proven counterclockwise (CCW) AFL presented with a typical ECG suggesting this mechanism. In contrast, 86.1% of nonsurgical patients demonstrated a typical ECG pattern for CCW AFL. In addition, we employed a reverse "U-curve" to facilitate radiofrequency delivery when ablating near the inferior vena cava ostium in the present study. Compared with the nonsurgical group, electroanatomical mapping showed the mean AFL cycle length was significantly longer (253.3 ± 40.4 vs. 234.1 ± 24.2 ms, p = 0.03) and the right atrium volume was larger (114.8 ± 26.0 vs. 97.5 ± 19.1 mL, p = 0.004) in the postsurgical group. Additionally, the procedural time (75.9 ± 21.3 vs. 61.6 ± 26.6 minutes, p = 0.03) and ablation time (53.0 ± 21.4 vs. 36.7 ± 25.6 minutes, p = 0.02) are much longer in the postsurgical group. However, the navigation index in the postsurgical group was significantly smaller (0.35 ± 0.08 vs. 0.43 ± 0.13, p = 0.01). Moreover, the acute and long-term success rates were comparable between the two groups. CONCLUSIONS: Catheter ablation of CTI-AFL with and without prior cardiac surgery guided by RMN are associated with high acute and long-term success rates, despite the procedural and ablation times are much longer in the postsurgical patients. However, ECG characteristics of the tachycardia may be misleading as they are more often atypical in patients after cardiac surgery.