Targeting miR-21 to Overcome P-glycoprotein Drug Efflux in Doxorubicin-Resistant 4T1 Breast Cancer.

Acquired resistance to chemotherapy is a major challenge in the treatment of triple-negative breast cancer (TNBC). Despite accumulated evidence showing microRNA-21 (miR-21) as a vital regulator of tumor progression, the role of miR-21 in modulating the multidrug resistance of TNBC remains obscure. In this study, we demonstrate that miR-21 affects chemoresistance in 4T1 TNBC cells in response to doxorubicin (DOX) by regulating the P-glycoprotein (P-gp) drug efflux pump. Overexpression of miR-21 in the 4T1 cells markedly reduced their sensitivity to DOX, impeding DOX-promoted cell death. We employed anti-miR-21 oligonucleotide conjugated with a PD-L1-binding peptide (P21) for targeted delivery to 4T1 tumor cells. The selective down-regulation of miR-21 in 4T1 TNBC led to the reversal of P-gp-mediated DOX resistance by up-regulating phosphatase and tensin homolog (PTEN). Our study highlights that miR-21 is a key regulator of drug efflux pumps in TNBC, and targeting miR-21 could enhance DOX sensitivity, offering a potential therapeutic option for patients with DOX-resistant TNBC.

Milk-derived extracellular vesicles enable gut-to-tumor oral delivery of tumor-activated doxorubicin prodrugs.

Rationale: Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Despite the current advancements in nanoparticle-mediated drug delivery, numerous anticancer drugs susceptible to the hostile gastrointestinal (GI) environment exhibit poor permeability across the intestinal epithelium, rendering them ineffective in providing therapeutic benefits. In this paper, we focus on harnessing milk-derived extracellular vesicles (mEVs) for gut-to-tumor oral drug delivery by leveraging their high bioavailability. Methods: The tumor-activated prodrug (a cathepsin B-specific cleavable FRRG peptide and doxorubicin, FDX) is used as a model drug and is complexed with mEVs, resulting in FDX@mEVs. To verify stability in the GI tract, prolonged intestinal retention, and enhanced trans-epithelial transport via neonatal Fc receptor (FcRn)-mediated transcytosis, intestinal transport evaluation is conducted using in vitro intestinal barrier model and mouse model. Results: FDX@mEVs form a stable nanostructure with an average diameter of 131.1 ± 70.5 nm and complexation processes do not affect the inherent properties of FDX. Orally administered FDX@mEVs show significantly improved bioavailability compared to uncomplexed FDX via FcRn-mediated transcytosis of mEVs resulting in increased tumor accumulation of FDX in tumor-bearing mouse model. Conclusions: After oral administration of FDX@mEVs, it is observed that remarkable antitumor efficacy in colon tumor-bearing mice without adverse effects, such as body weight loss, liver/kidney dysfunction, and cardiotoxicity.

Effective descriptor extraction strategies for correspondence matching in coronary angiography images.

The importance of 3D reconstruction of coronary arteries using multiple coronary angiography (CAG) images has been increasingly recognized in the field of cardiovascular disease management. This process relies on the camera matrix's optimization, needing correspondence info for identical point positions across two images. Therefore, an automatic method for determining correspondence between two CAG images is highly desirable. Despite this need, there is a paucity of research focusing on image matching in the CAG images. Additionally, standard deep learning image matching techniques often degrade due to unique features and noise in CAG images. This study aims to fill this gap by applying a deep learning-based image matching method specifically tailored for the CAG images. We have improved the structure of our point detector and redesigned loss function to better handle sparse labeling and indistinct local features specific to CAG images. Our method include changes to training loss and introduction of a multi-head descriptor structure leading to an approximate 6% improvement. We anticipate that our work will provide valuable insights into adapting techniques from general domains to more specialized ones like medical imaging and serve as an improved benchmark for future endeavors in X-ray image-based correspondence matching.

Dual-Action Protein-siRNA Conjugates for Targeted Disruption of CD47-Signal Regulatory Protein α Axis in Cancer Therapy.

A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and N-acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors. Conjugation of the SIRPα IgV domain protein to siRNAs enables tumor dash through CD47-mediated erythrocyte piggyback, primarily blocking the physical interaction between CD47 on cancer cells and SIRPα on phagocytes. After internalization of the vS-siCD47 conjugates within cancer cells, the detached free-standing anti-CD47 siRNAs subsequently attack CD47 through the RNAi mechanism. The dual-action approach of the vS-siCD47 conjugate effectively overcomes the "don't eat me" barrier and stimulates phagocyte-mediated tumor destruction, demonstrating a highly selective and potent CD47-blocking immunotherapy. This delivery strategy, employing IgV domain protein-siRNA conjugates with a dual mode of target suppression, holds promise for expanding RNAi applications beyond hepatocytes and advancing RNAi-based cancer immunotherapies for solid tumors.

Targeted delivery of anti-miRNA21 sensitizes PD-L1high tumor to immunotherapy by promoting immunogenic cell death.

Rationale: Growing evidence has demonstrated that miRNA-21 (miR-21) upregulation is closely associated with tumor pathogenesis. However, the mechanisms by which miR-21 inhibition modulates the immunosuppressive tumor microenvironment (TME) and improves tumor sensitivity to immune checkpoint blockade therapies remain largely unexplored. In this study, we demonstrate the precise delivery of anti-miR-21 using a PD-L1-targeting peptide conjugate (P21) to the PD-L1high TME. Methods: Investigating miR-21 inhibition mechanisms involved conducting quantitative real-time PCR, western blot, flow cytometry, and confocal microscopy analyses. The antitumor efficacy and immune profile of P21 monotherapy, or combined with anti-PD-L1 immune checkpoint inhibitors, were assessed in mouse models bearing CT26.CL25 tumors and 4T1 breast cancer. Results Inhibition of oncogenic miR-21 in cancer cells by P21 efficiently activates tumor suppressor genes, inducing autophagy and endoplasmic reticulum stress. Subsequent cell-death-associated immune activation (immunogenic cell death) is initiated via the release of damage-associated molecular patterns. The in vivo results also illustrated that the immunogenic cell death triggered by P21 could effectively sensitize the immunosuppressive TME. That is, P21 enhances CD8+ T cell infiltration in tumor tissues by conferring immunogenicity to dying cancer cells and promoting dendritic cell maturation. Meanwhile, combining P21 with an anti-PD-L1 immune checkpoint inhibitor elicits a highly potent antitumor effect in a CT26.CL25 tumor-bearing mouse model and 4T1 metastatic tumor model. Conclusions: Collectively, we have clarified a miR-21-related immunogenic cell death mechanism through the precise delivery of anti-miR-21 to the PD-L1high TME. These findings highlight the potential of miR-21 as a target for immunotherapeutic interventions.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.

Light-Triggered PROTAC Nanoassemblies for Photodynamic IDO Proteolysis in Cancer Immunotherapy.

While proteolysis-targeting chimeras (PROTACs) hold great potential for persistently reprogramming the immunosuppressive tumor microenvironment via targeted protein degradation, precisely activating them in tumor tissues and preventing uncontrolled proteolysis at off-target sites remain challenging. Herein, a light-triggered PROTAC nanoassembly (LPN) for photodynamic indoleamine 2,3-dioxygenase (IDO) proteolysis is reported. The LPN is derived from the self-assembly of prodrug conjugates, which comprise a PROTAC, cathepsin B-specific cleavable peptide linker, and photosensitizer, without any additional carrier materials. In colon tumor models, intravenously injected LPNs initially silence the activity of PROTACs and accumulate significantly in targeted tumor tissues due to an enhanced permeability and retention effect. Subsequently, the cancer biomarker cathepsin B begins to trigger the release of active PROTACs from the LPNs through enzymatic cleavage of the linkers. Upon light irradiation, tumor cells undergo immunogenic cell death induced by photodynamic therapy to promote the activation of effector T cells, while the continuous IDO degradation of PROTAC simultaneously blocks tryptophan metabolite-regulated regulatory-T-cell-mediated immunosuppression. Such LPN-mediated combinatorial photodynamic IDO proteolysis effectively inhibits tumor growth, metastasis, and recurrence. Collectively, this study presents a promising nanomedicine, designed to synergize PROTACs with other immunotherapeutic modalities, for more effective and safer cancer immunotherapy.

Diabetes Primes Neutrophils for Neutrophil Extracellular Trap Formation through Trained Immunity.

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5'-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5'-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.

Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy.

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD-L1 proteins, which leads to the uptake of LNPs into PD-L1 overexpressing cancer cells both in vitro and in vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, mRNA encoding phosphatase and tensin homolog (PTEN) is delivered via Pep LNPs to PTEN-deficient triple-negative breast cancers (TNBCs). Pep LNPs loaded with PTEN mRNA specifically promotes autophagy-mediated immunogenic cell death in 4T1 tumors, resulting in effective anticancer immune responses. This study highlights the potential of tumor-targeted LNPs for mRNA-based cancer therapy.

Oral TNF-α siRNA delivery via milk-derived exosomes for effective treatment of inflammatory bowel disease.

Oral administration facilitates the direct delivery of drugs to lesions within the small intestine and colon, making it an ideal approach for treating patients with inflammatory bowel disease. However, multiple physical barriers impede the delivery of oral RNA drugs through the gastrointestinal tract. Herein, we developed a novel oral siRNA delivery system that protects nucleic acids in extreme environments by employing exosomes derived from milk to encapsulate tumor necrosis factor-alpha (TNF-α) siRNA completely. The remarkable structural stability of milk-derived exosomes (M-Exos), as opposed to those from HEK293T cells, makes them exceptional siRNA carriers. Results demonstrate that milk exosomes loaded with TNF-α siRNA (M-Exo/siR) can effectively inhibit the expression of TNF-α-related inflammatory cytokines. Moreover, given that milk exosomes are composed of unique lipids with high bioavailability, orally administered M-Exo/siR effectively reach colonic tissues, leading to decreased TNF-α expression and successful alleviation of colitis symptoms in a dextran sulfate sodium-induced inflammatory bowel disease murine model. Hence, milk-derived exosomes carrying TNF-α siRNA can be effectively employed to treat inflammatory bowel disease. Indeed, using exosomes naturally derived from milk may shift the current paradigm of oral gene delivery, including siRNA.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015-2017.

BACKGROUND: Previous studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours. METHODS: We analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey. Conventional cardiovascular risk factors (blood pressure, lipid profiles, and fasting glucose), and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], and white blood cell counts [WBC]) were investigated in relation to the frequency of toothbrushing. RESULTS: The estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort equations was 13.7%, 9.1%, and 7.3% for participants who reported toothbrushing 0-1, 2, and ≥ 3 times a day, respectively. Both conventional risk factors and inflammatory markers were significantly associated with frequent toothbrushing. However, after adjusting potential confounding factors such as age, sex, comorbidities, and lifestyle behaviours, only inflammatory markers were remained as significant factors. CONCLUSIONS: Oral hygiene behaviours are closely linked to cardiovascular risk factors. This study suggests that reduced systemic inflammatory burden may explain the benefit of improved oral hygiene in terms of cardiovascular risk.

Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

BACKGROUND: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. METHODS: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5. RESULTS: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group. CONCLUSION: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734028.

Psychometric Properties of the Advance Care Planning Engagement Survey-9 in Cardiovascular and Metabolic Diseases.

The purpose of this study was to test the reliability and validity of the Advance Care Planning Engagement Survey-9 Korean version in patients with cardiovascular diseases or metabolic syndrome. In this cross-sectional study, data on advance care planning engagement, registration of advance directives and the intention, and sociodemographic characteristics were collected from 105 patients (mean age, 66.3 years) at 4 medical institutions. Cronbach α was used to test the reliability. Confirmatory factor analysis and independent t tests were used to test the validity. Cronbach α s for the total scale and the self-efficacy and readiness dimensions were .93, .82, and .97, respectively. In confirmatory factor analysis with 2 factors, all indices of model fit were acceptable: comparative fit index, 0.995; Tucker-Lewis index, 0.989; standardized root-mean-square residual, 0.024; root-mean-square error of approximation, 0.059; and factor loadings > 0.65. Patients who registered advance directives ( P < .001) or had the intention ( P < .001) had higher scores of the Advance Care Planning Engagement Survey-9 Korean version than their counterparts. The findings demonstrate that the Advance Care Planning Engagement Survey-9 Korean version was a reliable and valid instrument. Health care providers, including nurses, can use this instrument to assess and manage advance care planning engagement in Korean patients with cardiovascular diseases or metabolic syndrome.

Machine learning for predicting hepatitis B or C virus infection in diabetic patients.

Highly prevalent hepatitis B and hepatitis C virus (HBV and HCV) infections have been reported among individuals with diabetes. Given the frequently asymptomatic nature of hepatitis and the challenges associated with screening in some vulnerable populations such as diabetes patients, we conducted an investigation into the performance of various machine learning models for the identification of hepatitis in diabetic patients while also evaluating the significance of features. Analyzing NHANES data from 2013 to 2018, machine learning models were evaluated; random forest (RF), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO) along with stacked ensemble model. We performed hyperparameter tuning to improve the performance of the model, and selected important predictors using the best performance model. LASSO showed the highest predictive performance (AUC-ROC = 0.810) rather than other models. Illicit drug use, poverty, and race were highly ranked as predictive factors for developing hepatitis in diabetes patients. Our study demonstrated that a machine-learning-based model performed optimally in the detection of hepatitis among diabetes patients, achieving high performance. Furthermore, models and predictors evaluated from the current study, we expect, could be supportive information for developing screening or treatment methods for hepatitis care in diabetes patients.

Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery.

BACKGROUND: Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production. Because the active-targeting ability of drug carriers is essential to maximize therapeutic efficacy and minimize side effects, precise membrane functionalization strategies are required to enable tissue-specific delivery of milk exosomes with difficulty in post-isolation modification. METHODS: In this study, the membrane functionalization of a milk exosome platform modified using a simple post-insertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surface-tunable modifications for the delivery of tumor-targeting doxorubicin (Dox). The surface modification of mExo was achieved through the hydrophobic insertion of folate (FA)-conjugated lipids. RESULTS: We have confirmed the stable integration of functionalized PE-lipid chains into the mExo membrane through an optimized post-insertion technique, thereby effectively enhancing the surface functionality of mExo. Indeed, the results revealed that FA-modified mExo (mExo-FA) improved cellular uptake in cancer cells via FA receptor (FR)-mediated endocytosis. The designed mExo-FA selectively delivered Dox to FR-positive tumor cells and triggered notable tumor cell death, as confirmed by in vitro and in vivo analyses. CONCLUSIONS: This simple and easy method for post-isolation modification of the exosomal surface may be used to develop milk-exosome-based drug delivery systems.

Design of siRNA Bioconjugates for Efficient Control of Cancer-Associated Membrane Receptors.

Research on siRNA delivery has seen tremendous growth over the past few decades. As one of the major delivery strategies, siRNA bioconjugates offer the potential to enhance and extend the pharmacological properties of siRNAs while minimizing toxicity. In this paper, we suggest the development of a siRNA conjugate platform with peptides and proteins that are ligands of target receptors for cancer treatment. The siRNA bioconjugates target and block the receptor membrane proteins, enter the cells through receptor-mediated endocytosis, and inhibit the expression of that same target membrane receptor, thereby doubly controlling the function of the membrane proteins. The three kinds of bioconjugates targeting CD47, PD-L1, and EGFR were synthesized via two different copper-free click chemistry reactions. Results showed the cellular uptake of each conjugate, reduction of target gene expression, and efficient functional control of receptor proteins. This platform provides an effective approach for regulating membrane proteins in various diseases beyond cancer.

Structural Relationships Between Cognitive Function, Depressive Symptoms, Self-Care Confidence, and Maintenance in Patients With Heart Failure.

Introduction: In order to promote self-care maintenance behavior in patients with heart failure (HF), it is necessary to identify the direct and indirect effects of major latent variables. Objective: This study aimed to identify structural relationships between different domains of cognitive function, depression and self-care confidence, and self-care maintenance. Methods: This descriptive study involved a secondary analysis using data of 201 patients with HF from two observational studies in three hospitals in Korea. The structural equation model using AMOS version 24.0 was constructed to assess the relationships among the variables. The Seoul Neuropsychological Screening Battery was used to assess global cognition, immediate/delayed memory, and executive function, and the Self-Care of HF Index v.6.2. was used for self-care confidence and maintenance. Results: Self-care maintenance was affected by memory function with a significant direct effect (ß=.43, p = .006), as well as self-care confidence (ß=.70, p < .001). Memory function and global function indirectly affected self-care maintenance through self-care confidence (ß = -.37, p = .002; ß = .14, p = .030). Depressive symptoms also had an indirect effect through self-care confidence on self-care maintenance (ß = -.21, p = .005). Conclusion: This study confirmed that it is important to increase self-care confidence through supportive care and to maintain memory function for maintaining self-care in the chronic course of HF patients. In particular, this study suggests that it is necessary to perform periodic memory check-ups for chronic HF patients on an outpatient basis, and counseling and education are needed to improve memory and increase confidence in self-care.

Diagnostic Value of a Wearable Continuous Electrocardiogram Monitoring Device (AT-Patch) for New-Onset Atrial Fibrillation in High-Risk Patients: Prospective Cohort Study.

BACKGROUND: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation. OBJECTIVE: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHA2DS2-VASc) score had increased detection rates. METHODS: In this nonrandomized multicenter prospective cohort study, we enrolled 320 adults aged ≥19 years who had never experienced atrial fibrillation and whose CHA2DS2-VASc score was ≥2. The AT-Patch was attached to each individual for 11 days, and the data were analyzed for arrhythmic events by 2 independent cardiologists. RESULTS: Atrial fibrillation was detected by the AT-Patch in 3.4% (11/320) of patients, as diagnosed by both cardiologists. Interestingly, when participants with or without atrial fibrillation were compared, a previous history of heart failure was significantly more common in the atrial fibrillation group (n=4/11, 36.4% vs n=16/309, 5.2%, respectively; P=.003). When a CHA2DS2-VASc score ≥4 was combined with previous heart failure, the detection rate was significantly increased to 24.4%. Comparison of the recorded electrocardiogram data revealed that supraventricular and ventricular ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group compared with nonatrial fibrillation group (3.4% vs 0.4%; P=.001 and 5.2% vs 1.2%; P<.001), respectively. CONCLUSIONS: This study detected a moderate number of new-onset atrial fibrillations in high-risk patients using the AT-Patch device. Further studies will aim to investigate the value of early detection of atrial fibrillation, particularly in patients with heart failure as a means of reducing adverse clinical outcomes of atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04857268; https://classic.clinicaltrials.gov/ct2/show/NCT04857268.

Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis.

BACKGROUND: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. METHODS: Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. RESULTS: Of 184 patients who agreed to participate in the study, 151 were finally analyzed. Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63-0.80) for CCTA, 0.65 (95% CI, 0.56-0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70-0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55-0.71) for CCTA alone, 0.66 (0.58-0.74) for algorithm A, and 0.76 (0.68-0.82) for algorithm B. CONCLUSION: This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.