Intracardiac Echocardiography: An Invaluable Tool in Electrophysiological Interventions for Atrial Fibrillation and Supraventricular Tachycardia.

Researchers have investigated ways to develop optimal imaging techniques to increase the safety and effectiveness of electrophysiological (EP) procedures. Intracardiac echocardiography (ICE) is an advanced imaging tool that can directly visualize cardiac anatomical structures in high resolution, assess tissue heterogeneity and arrhythmogenic substrates, locate intracardiac catheters, monitor catheter-tissue contact and ablation injury in real-time, excluding intracardiac thrombi, and quickly detect procedural complications. Additionally, real-time imaging via ICE can be integrated with a three-dimensional (3D) electroanatomical mapping (EAM) system to reconstruct cardiac anatomy. This technique also promotes the development of zero-radiation EP procedures. Many EP studies and procedures have implemented ICE because it has several advantages over fluoroscopy and transesophageal echocardiography (TEE). ICE-guided EP procedures can be performed under conscious sedation; esophageal intubation and additional anesthesiologists are not required. Atrial fibrillation (AF) and supraventricular tachycardias (SVT) are the most common tachyarrhythmias in clinical settings. A comprehensive understanding of critical anatomical structures, such as the atrial septum, fossa ovalis (FO), and great heart vessels, is needed for the successful catheter ablation of these arrhythmias.

Comparative effectiveness and safety of DOACs vs. VKAs in treatment of left ventricular thrombus- a meta-analysis update.

BACKGROUND AND OBJECTIVE: Left ventricular thrombus (LVT) formation in patients with acute myocardial infarction (AMI) or cardiomyopathies is not uncommon. The optimal oral anticoagulation therapy for resolving LVT has been under intense debate. Vitamin K antagonists (VKAs) remain the anticoagulant of choice for this condition, according to practice guidelines. Evidence supporting the use of direct oral anticoagulants (DOACs) in the management of LVT continues to grow. We performed a systematic review and meta-analysis to compare the efficacy and safety of DOACs versus VKAs. METHODS: A comprehensive literature search was carried out in PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases in July 2023. The efficacy outcomes of this study were thrombus resolution, ischemic stroke, systemic embolism, stroke/systemic embolism, all-cause mortality, and adverse cardiovascular events. The safety outcomes were any bleeding, major bleeding, and intracranial hemorrhage. A total of twenty-seven eligible studies were included in the meta-analysis. Data were analyzed utilizing Stata software version 15.1. RESULTS: There was no significant difference between DOACs and VKAs with regard to LVT resolution (RR = 1.00, 95% CI 0.95-1.05, P = 0.99). In the overall analysis, DOACs significantly reduced the risk of stroke (RR = 0.74, 95% CI 0.57-0.96, P = 0.021), all-cause mortality (RR = 0.70, 95% CI 0.57-0.86, P = 0.001), any bleeding (RR = 0.75, 95% CI 0.61-0.92, P = 0.006) and major bleeding (RR = 0.67, 95% CI 0.52-0.85, P = 0.001) when compared to VKAs. Meanwhile, in the sub-analysis examining randomized controlled trials (RCTs), the aforementioned outcomes no longer differed significantly between the DOACs and VKAs groups. The incidences of systemic embolism (RR = 0.81, 95% CI 0.54-1.22, P = 0.32), stroke/systemic embolism (RR = 0.85, 95% CI 0.72-1.00, P = 0.056), intracranial hemorrhage (RR = 0.59, 95% CI 0.23-1.54, P = 0.28), and adverse cardiovascular events (RR = 0.99, 95% CI 0.63-1.56, P = 0.92) were comparable between the DOACs and VKAs groups. A subgroup analysis showed that patients treated with rivaroxaban had a significantly lower risk of stroke (RR = 0.24, 95% CI 0.08-0.72, P = 0.011) than those in the VKAs group. CONCLUSION: With non-inferior efficacy and superior safety, DOACs are promising therapeutic alternatives to VKAs in the treatment of LVT. Further robust investigations are warranted to confirm our findings.

Long-term outcomes of catheter ablation for ventricular arrhythmias: comparing techniques with and without intracardiac echocardiography - what matters?

BACKGROUND: The increasing use of intracardiac echocardiography (ICE) in the ablation of premature ventricular complexes (PVCs) has raised questions about its true efficacy and safety. METHODS: This retrospective study collected the periprocedural complications and PVC burden post ablation. The risk factors of PVC recurrence was further explored. RESULTS: The study included patients treated without ICE (control group, n = 451) and with ICE (ICE group, n = 155) from May 2019 to July 2022. The ICE group demonstrated significantly lower fluoroscopy times and X-ray doses. There were no major complications in the ICE group, and the difference in the occurrence of periprocedural complications between the groups was not statistically significant (p = 0.072). The long-term success rates were similar for the control and ICE groups (89.6% and 87.1%, respectively). The origin of PVCs was identified as the independent factor for ablation success. CONCLUSIONS: The use of ICE did not confer an advantage with regard to long-term success in PVCs ablation. To thoroughly evaluate the safety and effectiveness of ICE in PVCs ablation, a prospective, multicenter, randomized study is warranted.

Western blot normalization: Time to choose a proper loading control seriously.

Recent research has questioned the validity of housekeeping proteins in Western blot. Our present study proposed new ideas for Western blot normalization that improved the reproducibility of scientific research. We used the Gene Expression Omnibus (GEO) database and the web tool GEO2R to exclude unstable housekeeping genes quickly. In ischemic heart tissues, actin and tubulin changed significantly, whereas no statistically significant changes were observed in the expression of genes relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Besides, the reliability of GAPDH was further examined by Western blot. Additionally, unstable housekeeping genes were found in other animal models of cardiovascular medicine. We also found that sodium dodecyl sulfate and temperature significantly impacted the results of Ponceau S staining. Membranes stained with Ponceau S after immunodetection could avoid this interference, and the coefficients of variation for post-immunodetection staining are lower than those produced by GAPDH immunodetection. Overall, we described a new use of differential gene expression analysis and proposed a modified Ponceau S staining method, which provided researchers with a proper loading control for Western blot and hence could improve reproducibility in research.

The risk factors of thrombus formation and the effect of catheter ablation on repetitive thrombus formation in patients with atrial fibrillation: a single center retrospective study in China.

BACKGROUND: Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus. METHODS: (1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA. RESULTS: The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806-5.500; p < 0.001). Twenty-seven patients agreed to undergo TEE during follow-up, no clinical ischemic stroke events were recorded, no recurrent intracardiac thrombus formation was detected in patients, 15 patients maintained sinus rhythm (55.6%) during follow-up; successful CA significantly increased LAAFV (difference between latest evaluation prior to CA 17.46 ± 14.81 cm/s, p < 0.001). CONCLUSIONS: Persistent AF is the only independent risk factor for thrombus formation. Successful CA may improve the LAAFV and thereby decrease the risk of intracardiac thrombus formation.

Clinical Manifestations, Outcomes, and Mortality Risk Factors of Atrial-Esophageal Fistula: A Systematic Review.

INTRODUCTION: Atrial-esophageal fistula (AEF) is a rare but life-threatening complication of catheter ablation. The clinical presentation and mortality risk factors of AEF have not been fully elucidated. The aim of this study was to systematically review the clinical characteristics and prognosis of AEF. METHODS: PubMed was searched from inception to October 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement protocol. RESULTS: A total of 190 AEF patients were included. The mean age was 59.29 ± 11.67 years, 74.21% occurred in males, and 81.58% underwent radiofrequency ablation. AEF occurred within 30 days after ablation in 80.82% of patients and occurred later in patients presenting with neurological symptoms compared with other symptoms (median of onset time: 27.5 days vs. 16 days, p < 0.001). Clinical presentation included fever (81.58%) and neurological symptoms (80.53%). Chest computed tomography (abnormal rate of 91.24%) was the preferred diagnostic test, followed by magnetic resonance imaging of the brain (abnormal rate of 90.91%). Repeated testing improved diagnostic evaluation sensitivity. Distinctive imaging results included free air in the mediastinum (incidence rate of 81.73%) and air embolism of the brain (incidence rate of 57.53%). The overall mortality was 63.16%, with worse nonsurgical treatment outcomes compared with outcomes of surgical treatment (94.19% vs. 33.71%, p < 0.001). Conservative or stent intervention was an independent risk factor for mortality. Age (adjusted odds ratio, 1.063, p = 0.004), presentation with neurological symptoms (adjusted odds ratio, 5.706, p = 0.017), and presentation with gastrointestinal bleeds (adjusted odds ratio, 3.009, p = 0.045) were also predictors of mortality. CONCLUSIONS: AEF is a fatal ablation complication. AEF can be diagnosed using a combination of a clinical history of ablation, infection, or neurological symptoms and an abnormal chest CT. Our analysis supports that surgical treatment reduces the mortality rate.

The role of alcohol consumption on echocardiographic and electrophysiologic changes in atrial fibrillation.

BACKGROUND: A wealth of evidence suggests that alcohol consumption is a risk factor for atrial fibrillation (AF); however, the mechanisms underlying this association are unclear. This makes it challenging to develop therapeutic strategies in patients with AF attributed to alcohol consumption. PURPOSE: To investigate the echocardiographic and electrophysiologic changes caused by alcohol consumption in patients with AF. METHODS: The study was registered in Chinese Clinical Trial Registry (Registration number ChiCTR2000041575). Data on 134 consecutive non-valvular AF patients who underwent radiofrequency catheter ablation in our center was collected from April 1, 2019 to June 30, 2020. Patients were divided into no-alcohol (72) and alcohol groups [categorized into light (34), moderate (11) and heavy (17) alcohol consumption]. All patients underwent echocardiographic and electrophysiologic examinations for the assessment of left atrial (LA) strain, inter-atrial conduction, intra-atrial conduction, and atrial effective refractory period (ERP). RESULTS: Overall, the mean age was 61 ± 11 years and 87 (65%) were males. Compared with the no-alcohol group, impaired peak LA longitudinal strain, obvious inter-atrial conduction delay and increasing ERP dispersion were observed in the alcohol group. Intra-atrial conduction delay and ERP dispersion increased with increasing amounts of alcohol consumption. CONCLUSION: Alcohol consumption was associated with substantial abnormal echocardiographic and electrophysiologic changes in AF patients. These changes may contribute to the occurrence and progression of AF attributed to alcohol consumption, which may help in the development of new strategies for the prevention and management of AF. However further investigation is required.

Feasibility and safety of left atrial appendage occlusion guided by procedural fluoroscopy only: A pilot study.

BACKGROUND: Left atrial appendage occlusion (LAAO) is usually performed via the guidance of procedural transesophageal echocardiography (TEE) companied by general anesthesia (GA). OBJECTIVE: To investigate the feasibility and safety of LAAO guided by procedural fluoroscopy only. METHODS: The patients eligible for LAAO were enrolled into the current study and received implantation of either Watchman device or LAmbre device. The procedure was carried out with procedural fluoroscopy only and no companied GA; the position, shape, and leakage of the device were assessed by contrast angiography. TEE was performed after 3-month follow-up to evaluate the thrombosis, and leakage of device. RESULTS: Ninety-seven patients with atrial fibrillation (AF) with either Watchman device (n = 49) or LAmbre device (n = 48) were consecutively enrolled. Watchman device group was of lower CHA2 DS2 -VASc and HAS-BLED scores compared with LAmbre device groups (p < .05); the two groups had similar distributions of other baseline characteristics (p > .05), including procedural success rate (98.0% vs. 97.9%), mean procedure time, mean fluoroscopy time, total radiation dose, contrast medium dose, percentage of peri-device leakage. Pericardial effusions requiring intervention occurred in two of the Watchman group. TEE follow-up found no patient with residual leakage ≥5 mm at 3 months and no device related thrombosis (DRT). During the 22.0 ± 11.1 months follow-up, two patients experienced ischemic stroke. CONCLUSIONS: LAAO with the procedural imaging of fluoroscopy only exhibited the promising results of efficacy and safety. A prospective randomized multicenter study would be required to verify the observations in this study.

A systematic review and meta-analysis to determine the effect of oral anticoagulants on incidence of dementia in patients with atrial fibrillation.

AIMS: To assess the effect of oral anticoagulant (OAC) administration on incidence of dementia in patients with atrial fibrillation (AF) with Systematic review and meta-analysis. METHODS: We systematically searched the electronic databases including Pubmed, Embase, Cochrane library and ClinicalTrails.gov for relevant articles. The primary outcome was the incidence of dementia. The adjusted risk ratio (RR), odds ratio or hazard ratio were extracted and pooled by the random-effects models. Subgroup analysis was performed according to the setting observational window. Risk of bias was assessed using the Newcastle-Ottawa Scale, while publication bias was assessed by the Begg's and Egger's tests. RESULTS: Nine studies were included in this review (2 prospective and 7 retrospective observational studies, including 613,920 patients). The results presented the significant association between OAC therapy and the reduced risk of dementia compared with no treatment (RR [95% CI] = 0.72 [0.60, 0.86], I2  = 97.2%; P = .000). In the subgroup analysis with an observational window, the pooled RR became statistically non-significant (including four studies, RR [95% CI] = 0.75 [0.51, 1.10], I2  = 98.8%; P = .000). There is no significant risk of bias and publication bias. CONCLUSIONS: This study indicated the protective effect of OAC therapy for dementia in patients with AF. However, the results are limited because of high heterogeneity, inconsistent direction of effect in subgroup analysis with an observational window. Further prospective well-designed study is needed with longer follow-up duration in younger patients.

Is Epicardial Adipose Tissue Associated with Atrial Fibrillation Following Cardiac Surgery? A Systematic Review and Meta-Analysis.

BACKGROUND: Although epicardial adipose tissue (EAT) has been proven to be related to atrial fibrillation (AF) and post-ablation AF recurrence, the association between EAT and AF after cardiac surgery (AFACS) remains unclear. OBJECTIVE: This study was a systematic review and meta-analysis that assessed the relationship between EAT and AFACS. METHODS: Electronic databases were systematically searched for "atrial fibrillation" and "epicardial adipose tissue." The analysis was stratified according to the EAT measurement into three meta-analyses as (1) total EAT volume, (2) left atrial (LA)-EAT volume, and (3) EAT thickness. Standardized mean difference (SMD) was estimated using a random effects model. RESULTS: Eight articles with 10 studies (546 patients) were included. The meta-analysis revealed that EAT was higher in those with AFACS irrespective of the EAT measurement (total EAT volume: SMD = 0.56 mL, 95% confidence interval, CI = 0.56-1.10 mL, I2 = 0.90, P = .04; EAT thickness: SMD = 0.85 mm, 95% CI = 0.04-1.65 mm, I2 = 0.90, P = .04; LA-EAT volume: SMD = 0.57 mL, 95% CI = 0.23-0.92 mL, I2 = 0.00, P = .001). CONCLUSION: EAT was higher in patients with AFACS, measured either as volume or thickness.

Preparation of TTO/UF resin microcapsule via in situ polymerisation and modelling of its slow release.

For slow release of tea tree oil (TTO), TTO were encapsulated by urea-formaldehyde (UF) resin via in situ polymerisation. The effects of curing time and drying condition on particle size, and TTO loading of the TTO/UF microcapsules were investigated. The results indicated that TTO/UF resin microcapsules with curing time of 80 min had narrow size distribution and good wall cover. Drying at ambient was better to maintain the TTO content than drying at oven. The loading of TTO with curing time of 80 min can be up to 45 wt.% of the mass-proportion to the prepared microcapsules, and more than 90 wt.% of the loaded TTO could be sustainably released in about 5 days. Moreover, the release kinetics of TTO/UF microcapsules was well described by Ritger-Peppas model, revealing non-Fickian diffusion. Promisingly, TTO/UF microcapsules with good stability can be used as a slow release vehicle for antibacterial application.

Successful catheter ablation of atrial fibrillation improves but not reverses the abnormalities of left atrial mechanics and energy loss.

BACKGROUND: Dissipative energy loss (EL), a new index to quantify the inefficient blood flow, has not been explored within left atrium (LA) in patients with atrial fibrillation (AF). We aimed to study the intra-atrial flow and mechanics in patients with AF before and after successful catheter ablation by evaluating EL and LA global longitudinal strain (LAS). METHODS: In our study, there were 53 patients undergoing catheter ablation for AF at baseline (AF group) and 33 age- and sex-matched controls. They were both assessed of LA EL using vector flow mapping (VFM) and of LAS using two-dimensional tracking (2DTT) during systole (sys), early diastole (ed), and atrial contraction phase (ac). Out of 53 patients, 37 patients who sustained sinus rhythm and carried out the echocardiographic examination at 3 and 6 months follow-up were evaluated of change in EL and LAS. The independent predictors of EL during three phases in AF group were performed using stepwise multivariate linear regression analyses. RESULTS: Left atrium EL and LAS among all phases in AF group were significantly lower than controls (all P < 0.01). During follow-up, LASsys and LASac both significantly improved at 3 and 6 months (both P < 0.01), and ELac significantly increased after 6 months (P < 0.05); ELsys, ELed and LASed were no significant change; EL and LAS among all phases were no normalized during follow-up. The independent predictors of EL were: for ELsys, BSA (P = 0.004) and LASac (P = 0.025); for ELed, E (P = 0.001) and A (P = 0.014); for ELac, E/A (P < 0.001). CONCLUSION: Vector flow mapping and 2DTT revealed impaired intra-atrial flow and mechanics. Successful catheter ablation for AF slightly improves but not reverses the aforementioned impairment, indicating the continuous LA dysfunction.

TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway.

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

A review on regulation of DNA methylation during post-myocardial infarction.

Myocardial infarction (MI) imposes a huge medical and economic burden on society, and cardiac repair after MI involves a complex series of processes. Understanding the key mechanisms (such as apoptosis, autophagy, inflammation, and fibrosis) will facilitate further drug development and patient treatment. Presently, a substantial body of evidence suggests that the regulation of epigenetic processes contributes to cardiac repair following MI, with DNA methylation being among the notable epigenetic factors involved. This article will review the research on the mechanism of DNA methylation regulation after MI to provide some insights for future research and development of related drugs.

Iron deficiency: prevalence, mortality risk, and dietary relationships in general and heart failure populations.

Background: Iron deficiency (ID) is the most common nutritional deficiency, with little research on its prevalence and long-term outcomes in the general population and those with heart failure (HF). Both the relationships between dietary iron and ID, as well as dietary folate and ID, are understudied. Methods: We used data from the National Health and Nutrition Examination Survey from 1999 to 2002 to investigate the prevalence, prognosis, and relationship between dietary and ID defined by different criteria in the general population (n = 6,660) and those with HF (n = 182). Results: There was no significant difference in the prevalence of ID between HF patients and the general population after propensity score matching. Transferrin saturation (TSAT) <20% was associated with higher 5-year all-cause mortality (HR: 3.49, CI: 1.40-8.72, P = 0.007), while ferritin <30 ng/ml was associated with higher 10-year (HR: 2.70, CI: 1.10-6.67, P = 0.031) and 15-year all-cause mortality (HR: 2.64, CI: 1.40-5.00, P = 0.003) in HF patients. Higher dietary total folate but dietary iron reduced the risk of ID (defined as ferritin <100 ng/ml) in HF patients (OR: 0.80; 95% CI: 0.65-1.00; P = 0.047). Conclusions: The prevalence of ID was identical in HF and non-HF individuals. Ferritin <30 ng/ml was associated with long-term outcomes whereas TSAT <20% was associated with short-term prognosis in both the general population and HF patients. A diet rich in folate might have the potential for prevention and treatment of ID in HF patients.

Comparison of Efficacy and Safety Between Dronedarone and Amiodarone Used During the Blind Period in Patients with Atrial Fibrillation After Catheter Ablation.

Background: Dronedarone is an effective drug for maintaining the sinus rhythm in patients with atrial fibrillation (AF). The efficacy and safety of dronedarone versus amiodarone in patients with AF after catheter ablation (CA) needs more evidence. We retrospectively compared the efficacy and safety of dronedarone and amiodarone in our hospital. Methods: Patients who underwent CA from January 2021 to January 2022 and used dronedarone (n=229) or amiodarone (n=202) during the blind period were enrolled. The recurrence of AF in post-and during the blanking period was compared between the groups; the rehospitalization for re-ablation and adverse drug events (ADE) were also calculated. Results: During an average follow-up period of 14.28 months, the long-term recurrence rate of AF did not differ significantly between the amiodarone group and dronedarone group (22.71% vs 21.29%, hazard ratio [HR], 1.033, 95% confidence interval [CI], 0.661-1.614; p=0.888). The recurrence rate in the blanking period also showed no statistically significant differences between the amiodarone group and dronedarone group (9.90% vs 14.41%, HR, 0.851; 95% CI, 0.463-1.564; p=0.604). The re-hospitalization rates for re-ablation between two groups did not differ between the amiodarone group and dronedarone group (4.65% vs 13.46%; p =0.144). The incidence of ADE was higher in the dronedarone groups than that in the amiodarone group (16.59% vs 5.45%, p <0.001). The main adverse drug events in the dronedarone and amiodarone groups were gastrointestinal (6.99%) and bradycardia (2.48%), respectively. Conclusion: Compared to the amiodarone group, the dronedarone group had a similar blank-period and long-term recurrence rate of AF and a higher incidence of ADE.

Research on the local regional similarity of automatic fingerprint identification system fingerprints based on close non-matches in a ten million people database-Taking the central region of whorl as an example.

The local regional similarity of fingerprints has always been a hot issue in the field of fingerprint research. With the increasing size of ten-print databases, the appearance of close non-matches (CNMs) in automatic fingerprint identification system (AFIS) candidate lists has attracted increasing attention from forensic science departments worldwide. In this study, three categories (high-, medium-, and low-level) of standards for CNMs were established and 60 whorl samples were marked with different numbers of minutiae to explore the occurrence and influencing factors of CNMs in AFIS candidate lists based on a ten million people database. The results showed that all prints could be found with their corresponding CNMs. The average occurrence rate of CNMs for every query was 52.7% in the top 100 lists, and the most similar CNM was exactly the same in the local area of 12 coincidence points. CNMs appeared more in the middle and lower parts of the central region of the whorl. Moreover, shorter C2C distances and the same finger number and hand led to more CNMs being inspected. CNMs with higher similarity required a more extensive regional area and smaller minutiae density. We concluded that CNMs have a high occurrence rate in large-scale databases and many factors are closely related to them. Fingerprint examiners and researchers need to strengthen their understanding of CNMs to avoid the occurrence of misidentification like the Madrid bombings.

Sodium Butyrate Ameliorates Type 2 Diabetes-Related Sarcopenia Through IL-33-Independent ILC2s/IL-13/STAT3 Signaling Pathway.

Purpose: Sarcopenia has been described as a new complication of type 2 diabetes mellitus (T2DM). T2DM and sarcopenia impact each other, resulting in a variety of adverse outcomes such as frailty, disability, poor quality of life and increased mortality. Sodium butyrate (NaB) is reported to play a protective role against T2DM. The present study aimed to investigate whether NaB could ameliorate T2DM-related sarcopenia and the underlying mechanisms. Materials and Methods: The male db/db mice at 7-weeks were used as T2DM-related sarcopenia animal model with C57BL/6J mice as control. Mice were grouped according to whether they received NaB orally as follows: C57BL/6J+water group, C57BL/6J+NaB group, db/db+water group, and db/db+NaB group. Then, db/db mice receiving NaB orally were administered with inhibitors of group 2 innate lymphocytes (ILC2s), anti-CD90.2 by intraperitoneal injection divided into db/db+NaB+PBS group and db/db+NaB+anti-CD90.2 group. NaB dissolved in water at 150 mM. The skeletal muscle mass was measured by dural X-ray (DXA) test. ILC2s in spleen and skeletal muscle were evaluated by flow cytometry. The expressions of IL-33, IL-13, STAT3, P-STAT3, GATA-3 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) were assessed by ELISA or WB. The morphology of skeletal muscle fibers was assessed by immunofluorescence staining. Results: The proportion of ILC2s and the expressions of ILC2s markers IL-13 and GATA-3 were all significantly decreased in db/db mice, and these changes were improved by NaB. NaB increased the proportion of slow-twitch fibers in gastrocnemius, thus partially reversing the reduced exercise capacity of db/db mice. The expression of slow-twitch fibers marker PGC-1α induced by NaB was increased via activation of ILC2s/IL-13/STAT3 pathway. On the other way, IL-33 was not necessary for the activation of ILC2s/IL-13/STAT3 pathway. After depletion of ILC2s by anti-CD90.2, the ameliorating effect of NaB on T2DM-related sarcopenia was partially antagonized. Conclusion: These results indicated that NaB could ameliorate type 2 diabetes-related sarcopenia by activating IL-33-independent ILC2s/IL-13/STAT3 signaling pathway.

Direct Oral Anticoagulants versus Vitamin K Antagonists in Cirrhotic Patients with Atrial Fibrillation: Update of Systematic Review and Meta-Analysis.

BACKGROUND: Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC). OBJECTIVE: This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC. METHODS: A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3. RESULTS: Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08). CONCLUSION: DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

Efficacy and Safety of NOACs Compared With VKAs for Patients With Atrial Fibrillation After Transcatheter Aortic Valve Implantation: A System Review and Meta-Analysis.

Novel oral anticoagulants (NOACs) are preferentially recommended in patients with nonvalvular atrial fibrillation (AF) for stroke prevention over vitamin K antagonists (VKAs). However, the evidence regarding the efficacy and safety of NOACs versus VKAs after transcatheter aortic valve implantation (TAVI) in patients with AF is very rare. Pubmed, Embase, Web of science, and Cochrane Databases were searched for eligible studies published before May 19, 2022. A total of 11 studies were included in this meta-analysis involving 27 107 patients. Regarding primary outcomes, there were no differences between NOACs and VKAs in all-cause mortality (RR: 0.84, 95% CI: (0.69, 1.02)) and stroke (RR: 1.00, 95% CI: (0.85, 1.19)). With respect to secondary outcomes, NOACs were associated with reduced incidence of bleeding (RR: 0.77, 95% CI: (0.71, 0.83)) and intracranial bleeding (RR: 0.57, 95% CI: (0.39, 0.83)), whereas no significant differences were found in major or life-threatening bleeding (RR: 0.98, 95% CI: (0.82, 1.17)) and myocardial infarction (RR: 1.37, 95% CI: (0.83, 2.26)). Our meta-analysis revealed the safety and efficacy of NOACs may be superior to VKAs in AF patients undergoing TAVI.