Prevalence and associated factors of sexting among Taiwanese adolescents.

This study utilized a large-scale representative sample to explore the prevalence of sexting and its associated factors among adolescents in Taiwan. A total of 12,954 students in grade 5-12 countrywide were randomly selected to answer the sexting module of an online survey. 13.7% of the respondents reported having ever received sexts on cellphone, and 2.0% had sent sexts to others. The prevalence was higher among older adolescents. Gender differences were also found, in which female students were more likely to receive sexts (15.8% vs. 11.7%), while male students were at higher risk of sending sexts to others (2.9% vs. 1.1%). A series of hierarchical logistic regression were further performed to examine the associations between potential factors and receiving/sending sexts as the outcome variables. Age, gender, and time spending on texting were significantly associated with receiving and ending sexts. Online respect was found positively associated with receiving sexts but negatively associated with sending them. Privacy awareness was found not significantly associated with sexting. As the first national survey on this growing issue in Taiwan, the results of the present study highlighted the existence of sexting among local youth. Practice and policy implications were discussed.

MEMS-based meta-emitter with actively tunable radiation power characteristic.

We propose a meta-emitter based on micro-electro-mechanical system (MEMS) technology. The main structure of the meta-emitter unit cell is composed of four symmetrically split crosses of Au and SiO2 bilayer cantilevers. By changing the size of the cantilevers, this MEMS-based meta-emitter can realize the tunable perfect absorption, and the absorption spectrum is within the longwave infrared (LWIR) wavelength from 8.90 to 11.90 µm. When the surface temperature of the meta-emitter rises, the electrothermal actuation mechanism is performed through the different thermal expansion coefficient (TEC) of the bilayer cantilevers. Therefore, the cantilevers will be bent downward and the bending height of the cantilevers decreases linearly. In such case, the peak value of thermal radiation power can be tuned from the wavelength of 9.52 µm to 10.48 µm when the temperature of meta-emitter is increased from 293 to 1290 K. This proposed MEMS-based meta-emitter is an excellent LWIR light source and has potential application prospects in gas sensing, infrared spectroscopy analysis, medical care and so on.

Microelectromechanical System-Based Reconfigurable Terahertz Metamaterial for Polarization Filter, Switch, and Logic Modulator Applications.

The terahertz (THz) metamaterials integrated with microelectromechanical systems (MEMS) have led to the realization of dynamic control in amplitude, phase, polarization, and spin angular momentum of the THz wave. In this study, we demonstrate an MEMS-based reconfigurable THz metamaterial (RTM) composed of a split ring resonator (SRR) for real-time modulation of THz wave. By gradually increasing the polarization angle of the incident THz wave, the resonant frequency of SRR switches from 0.74 to 1.16 THz, and the maximum modulation depth is more than 70%. When the MEMS-based RTM is actuated by different DC bias voltages, the polarization-dependent transmission intensity and resonant frequency of the device can be actively tuned. MEMS-based RTM shows logical function characteristics that can be used for logic modulators by performing the driving voltages and polarization states as 2-bit input signals and quantizing the transmission response as "on" and "off" states. The logic gates of "NAND" are at 0.439 THz and "AND" is at 0.732 THz. These results offer potential applications for the proposed MEMS-based RTM in tunable and reconfigurable polarization filters, optical switches, programmable logic modulators, and so on.

Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases.

AIMS: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2+ cancers. The role of protein tyrosine phosphatases (PTPs) in trastuzumab resistance is not well understood. In this study, we aim to identify pivotal PTPs affecting trastuzumab resistance and devise a novel counteracting strategy. METHODS: Four public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2+ breast cancer. Tyrosine kinase (TK) arrays were used to identify kinases that linked to protein tyrosine phosphate receptor type O (PTPRO)-enhanced trastuzumab sensitivity. The efficacy of small activating RNA (saRNA) in trastuzumab-conjugated silica nanoparticles was tested for PTPRO upregulation and resistance mitigation in cell models, a transgenic mouse model, and human cancer cell line-derived xenograft models. RESULTS: PTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed "undruggable," was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting trastuzumab resistance. CONCLUSIONS: Antibody-conjugated saRNA represents an innovative approach for targeting "undruggable" PTPs.

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.

Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as "undruggable" targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development.

The association between acute myocardial infarction and subsequent diagnosis of breast cancer: a nationwide, population-based cohort study.

Coronary artery disease (CAD) such as acute myocardial infarction (MI) share several common risk factors with cancers, and each disease may influence the prognosis of the other. Recently, acute MI was demonstrated to accelerate the outgrowth of preexisting breast cancer cells but the risk of breast cancer after MI remains unclear. This study aimed to investigate the association between acute MI and a subsequent diagnosis of breast cancer. Female patients with and without a history of acute MI were identified from nationwide databases in Taiwan. Patients with a diagnosis of cancer, MI or CAD prior to the study period were excluded. After reducing confounding through inverse probability of treatment weighting, we compared the incidence of newly diagnosed breast cancer between patients with a history of acute MI and those without. As a result, a total of 66,445 female patients were obtained, including 15,263 patients with a history of acute MI and 51,182 patients without. The incidences of breast cancer during follow-up were 1.93 (95% confidence interval [CI] 1.78-2.09) and 1.80 (95% CI 1.67-1.93) per 1,000 person-years for patients with and without a history of acute MI, respectively. The hazard ratio (HR) was 1.05 (95% CI 0.78-1.41, P = 0.756). In subgroup analysis, breast cancer risk was significantly associated with acute MI in patients using antidiabetic drugs (HR 1.27; 95% CI 1.02-1.58) and in low to moderate urbanization levels (HR 1.28; 95% CI 1.06-1.53). In conclusion, the risk of newly diagnosed breast cancer was not increased in patients with acute MI when compared to general population without MI or CAD.

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey.

Introduction: Atherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood. Methods: An analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis. Results: A total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34-2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50-0.76, p < 0.001). Moreover, it is evident that AAC can be predicted more accurately when combined with SBP ≥130 mmHg and a low fetuin-A level (<358 µg/ml: aOR 5.39, 95% CI 3.21-9.08) compared with the reference. Conclusion: Low fetuin-A levels are significantly correlated with AAC while there is an increased association between vascular calcification and coexisting hypertension.

Endodontic apical surgery with novel endoscope: Three-case series.

Successful apical surgery relies on effective magnification and illumination. In the field of endodontics, the microscope has emerged as the predominant tool for meeting these requirements. The rigid endoscope is also a valuable instrument in apical surgery. This study introduces three cases demonstrating the application of endoscope technology in endodontic apical surgery. The first case employs a soft endoscope for treating an anterior tooth with apical periodontitis, the second integrates an endoscope with new attachments for a premolar, and the third combines an endoscope, attachments and navigation for the lower first molar surgery. It revealed that endoscopes offer certain advantages that are not achievable with microscope-assisted surgery, these cases had a great outcome. In the future, a broader application of endoscopic technology in various procedures is anticipated.

Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine.

Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.

Stretchable Dual-Axis Terahertz Bifocal Metalens with Flexibly Polarization-Dependent Focal Position and Direction.

Varifocal lenses are essential components in any optical system, while traditional lenses suffer from bulky volume, fixed focal position, and limited working spectra. As well-arranged subwavelength structures, metalenses overcome the abovementioned obstacles and exhibit merits of ultrathin thickness, flexible focal length, and multifocus. The electromagnetic responses of metasurfaces, including metalens, rely on the phase distributions of phase-shifting elements. The steerable focal direction is investigated to obtain the combinations of focusing and anomalous refraction phase distribution. To fully explore the flexibility of focal length and direction, seven designs of double layers of terahertz (THz) bifocal metalenses are proposed and investigated in this study. They exhibit dependent and independent relationships of tunable focal length and direction with flexible tuning mechanisms. Along with polarization multiplexing, two different focuses can be obtained when the incident waves are x-linear and y-linear polarization states, respectively. The simulation results agreed well with the theoretical predictions. These designs provide a new method to modulate the focal position precisely with promising applications in wireless communication, imaging, and on-chip optical integration systems.

Leadless pacemaker implementation at the right atrial appendage apex: An initial preclinical assessment.

OBJECTIVE: This study evaluates the feasibility and efficacy of implanting a leadless pacemaker at the right atrial appendage (RAA) in a preclinical minipig model, aiming to address the limitations of atrial pacing with current leadless devices like the Medtronic Micra, which is typically used for right ventricular implantation. METHODS: Four minipigs, each with a median body weight of 45.8 ± 10.0 kg, underwent placement of the Micra transcatheter pacing system (TPS) via the right femoral vein into the RAA apex. The pacing performance was assessed over 1-week (short-term) and 3-month (long-term) periods. OUTCOMES: The initial findings indicated successful implantation, with satisfactory intrinsic R-wave amplitudes and pacing threshold. In the following period, the sensitivity, threshold, and impedance were stable with time. Notably, upon explanation at 3 months, a deep myocardial penetration by the device was observed, necessitating a redesign for safe long-term use in a growing subject's heart. CONCLUSION: While initial results suggest that RAA apex placement of the Micra TPS is promising for potential inclusion in a dual-chamber pacing system, the issue of myocardial penetration highlights the need for device redesign to ensure safety and effectiveness in long-term applications.

Peripheral Blood Inflammatory Markers as A Reliable Predictor of Gastric Mucosal Metaplasia Change in the Middle-aged Population.

Purpose: The study aims to evaluate the efficacy of peripheral blood inflammatory markers as clinical predictors for gastric intestinal metaplasia (IM), a known precursor to gastric cancer. This research investigates the potential of these markers to serve as reliable indicators for detecting gastric IM. Methods: A retrospective cohort study was conducted on 59,143 individuals who underwent checkups at the Taoyuan Chang Gung Memorial Hospital Health Clinic Center from 2010 to 2014. Of these, 11,355 subjects who received gastroscopic biopsies were recruited. After omitting cases with incomplete blood data, the sample was narrowed to 10,380 participants. After exclusion and propensity score matching, subjects in the group with IM and control patients without IM were balanced and included in the study. These subjects were stratified by gender and age, and predictors such as the Systemic Inflammation Response Index (SIRI), Systemic Immune Inflammation Index (SII), and Monocyte-to-Lymphocyte Ratio (MLR) were evaluated. Multivariate logistic regression models were employed to analyze the presence or absence of IM accurately. Results: Out of the 10,380 subjects, 2,088 (20.1%) were diagnosed with IM, while 8,292 (79.9%) did not have IM. In our analysis, inflammation indices were found to have a limited impact on younger patients. For middle-aged and elderly individuals, SII showed statistical significance for predicting IM in males (p=0.0019), while SIRI and MLR were significant for females (SIRI p=0.0001, MLR p=0.0009). Additionally, the Area Under the Curve (AUC) value indicated that inflammation indices were more influential in females (55.1%) than males. Conclusions: The study results reveal that peripheral blood inflammatory markers could be useful in predicting gastric mucosal metaplasia changes, particularly in middle-aged and elderly populations. Although the markers' predictive power varies with gender, they represent a significant step forward in the non-invasive detection of gastric IM. This could aid in the early identification and management of precancerous conditions.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

BACKGROUND: Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. METHODS AND RESULTS: Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). CONCLUSIONS: Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Syphilis and cardiovascular risk: a Taiwanese registry.

BACKGROUND AND AIMS: Studies on the impact of syphilis on the cardiovascular system in large populations are limited. This study investigated the effects of syphilis on cardiovascular outcomes. METHODS: Medical records from 2010 to 2015 were retrieved from the Taiwan National Health Insurance Research Database, linked to the Notifiable Infectious Diseases database from the Taiwan Centers for Disease Control. Patients with syphilis were identified, excluding those with missing information, under 20 years of age, or with a history of human immunodeficiency virus infection, acute myocardial infarction, heart failure, aortic regurgitation, replacement of the aortic valve, aneurysm and/or dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, and venous thromboembolism. Primary outcomes included new-onset acute myocardial infarction, heart failure, aortic regurgitation, aneurysm and dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, cardiovascular death, and all-cause mortality. RESULTS: A total of 28 796 patients with syphilis were identified from 2010 to 2015. After exclusions and frequency matching, 20 601 syphilis patients and 20 601 non-syphilis patients were analysed. The relative rate (RR) was utilized in the analysis, as the competing risk of death was not considered. Compared with patients without syphilis, patients with syphilis had increased risks of acute myocardial infarction (RR 38%, 95% confidence interval [CI] 1.19-1.60, P < .001), heart failure (RR 88%, 95% CI 1.64-2.14, P < .001), aortic regurgitation (RR 81%, 95% CI 1.18-2.75, P = .006), atrial fibrillation (RR 45%, 95% CI 1.20-1.76, P < .001), ischaemic stroke (RR 68%, 95% CI 1.52-1.87, P < .001), haemorrhagic stroke (RR 114%, 95% CI 1.74-2.64, P < .001), venous thromboembolism (RR 67%, 95% CI 1.23-2.26, P = .001), cardiovascular death (RR 155%, 95% CI 2.11-3.08, P < .001), and all-cause death (RR 196%, 95% CI 2.74-3.19, P < .001) but not for aneurysm and dissection of the aorta. CONCLUSIONS: This study demonstrates that patients with syphilis have a higher risk of cardiovascular events and all-cause mortality compared with those without syphilis.

VISTA drives macrophages towards a pro-tumoral phenotype that promotes cancer cell phagocytosis yet down-regulates T cell responses.

BACKGROUND: VISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation. METHODS: Macrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34+ cell-derived monocytes, were used in phagocytosis assay using B lymphoma target cells opsonized with Rituximab. PBMC-derived macrophages were used to assess the correlation between phagocytosis and VISTA expression. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay were performed to analyze the impact of VISTA on other checkpoints and M1/M2-like macrophage biology. Additionally, flow cytometry was used to assess the frequency of CD14+ monocytes expressing VISTA in PBMCs from 65 lymphoma patients and 37 healthy donors. RESULTS: Ectopic expression of VISTA in the monocytic model cell line THP-1 or in primary monocytes triggered differentiation towards the macrophage lineage, with a marked increase in M2-like macrophage-related gene expression and decrease in M1-like macrophage-related gene expression. VISTA expression in THP-1 and monocyte-derived macrophages strongly downregulated expression of SIRPα, a prominent 'don't eat me' signal, and augmented phagocytic activity of macrophages against cancer cells. Intriguingly, expression of VISTA's extracellular domain alone sufficed to trigger phagocytosis in ∼ 50% of cell lines, with those cell lines also directly binding to recombinant human VISTA, indicating ligand-dependent and -independent mechanisms. Endogenous VISTA expression was predominantly higher in M2-like macrophages compared to M0- or M1-like macrophages, with a positive correlation observed between VISTA expression in M2c macrophages and their phagocytic activity. VISTA-expressing macrophages demonstrated a unique cytokine profile, characterized by reduced IL-1ß and elevated IL-10 secretion. Furthermore, VISTA interacted with MHC-I and downregulated its surface expression, leading to diminished T cell activation. Notably, VISTA surface expression was identified in monocytes from all lymphoma patients but was less prevalent in healthy donors. CONCLUSIONS: Collectively, VISTA expression associates with and drives M2-like activation of macrophages with a high phagocytic capacity yet a decrease in antigen presentation capability to T cells. Therefore, VISTA is a negative immune checkpoint regulator in macrophage-mediated immune suppression.

Effect of His Bundle Pacing on Abnormal Myocardial Fatty Acid and Glucose Metabolism Induced by Right Ventricular Pacing.

BACKGROUND: Metabolic disorder is noted for pacing-induced cardiomyopathy. The benefits of His bundle pacing over right ventricular (RV) pacing in preventing pacing-induced cardiomyopathy from a metabolic perspective are yet to be fully understood. METHOD AND RESULTS: Three pig groups were established for this study: sham control, RV pacing (RV pacing for 6 months), and His pacing (RV pacing for 6 months, followed by His bundle pacing for 3 months). Complete atrioventricular block was created in the last 2 groups. Left ventricular function and dyssynchrony were assessed via echocardiography, while proteins linked to metabolism, endoplasmic reticulum stress, and inflammation in left ventricular myocardium were examined. The RV pacing group had significantly more left ventricular mechanical dyssynchrony compared with the other groups. The RV pacing group exhibited triglyceride and diacylglycerol accumulation in cardiomyocytes and higher expression of binding immunoglobulin protein and tumor necrosis factor-α than the other groups. Additionally, the expression of CD36 was activated, while the expression of hormone-sensitive lipase was downregulated in the RV pacing group compared with the His pacing and sham control groups. Furthermore, the expressions of GLUT4 and pyruvate dehydrogenase were higher in the RV pacing group than the sham control and His pacing groups. Notably, the abnormal fatty acid and glucose metabolic pathways in the left ventricular myocardium during RV pacing could be corrected by His bundle pacing. CONCLUSIONS: His bundle pacing can mitigate the abnormal metabolism disorders, endoplasmic reticulum stress, and inflammation induced during RV pacing and may contribute to the superiority of conduction system pacing over RV pacing in reducing heart failure hospitalization.

Direct Functionalization of Polysaccharide-Based Xylan Phenyl Carbonate Nanoparticles with Tumor Cell Specific Antibodies.

An efficient and easy-to-use approach is presented for obtaining biocompatible polysaccharide-based nanoparticles (NP) that can act as tumor-specific drug delivery agents. Two antibodies are directly immobilized onto reactive xylan phenyl carbonate (XPC) NP; namely Cetuximab (CTX) that binds to human epidermal growth factor receptor (EGFR) and Atezolizumab (ATZ) that binds to programmed death-ligand 1 (PD-L1). High coupling efficiency (up to 100 %) are achieved without any pre-activation and no aggregation occurs during antibody immobilization. By quartz crystal microbalance experiments with dissipation monitoring (QCM-D), flow cytometry assays, and confocal laser scanning microscopy imaging it is demonstrated that the functionalized XPC-NP specifically bind to cells carrying the corresponding antigens. Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ).

Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete atrioventricular block pig model.

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.

Cardiovascular and renal outcomes in patients with atrial fibrillation and stage 4-5 chronic kidney disease receiving direct oral anticoagulants: a multicenter retrospective cohort study.

The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.