Background/Aims: Rectal hyposensitivity (RH), as defined by the London Classification, has been linked to sensory dysfunction caused by diabetes mellitus and Parkinson’s disease (PD); however, its clinical interpretation has not been sufficiently validated. In this study, we aim to explore the correlations between rectal sensory thresholds and the clinical characteristics of patients with functional defecatory disorders. Methods: We reviewed data from patients who underwent high-resolution anorectal manometry and acquired their clinical characteristics using a standardized questionnaire. The associations between RH based on either 1 (borderline RH) or 2 (RH) abnormal rectal sensory thresholds and patients’ clinical and demographic characteristics were analyzed using linear and logistic regression models in the overall sex-stratified populations. Results: We enrolled 2540 patients, of whom 1046 (41.2%) were men. Overall, 150 (5.9%) patients were diagnosed with RH, whereas 422 (16.6%) had borderline RH. Multivariate linear regression analysis revealed that the Cleveland Clinic Constipation Score (CCCS) increased linearly with the increase in the number of abnormal rectal sensory thresholds (effect per threshold: 0.900 [standard deviation: 0.188]). Upon stratification by sex, borderline RH was positively associated with diabetes mellitus, PD, and CCCS (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [1.08, 4.15]; aOR = 1.49 [1.03, 2.14]; aOR = 1.03 [1.01, 1.05], respectively) in women. However, RH was positively associated with only the CCCS. Conclusions Defining RH based on 1 or more abnormal sensory thresholds showed better clinical correlation with patient characteristics. However, further prospective studies are needed to validate these findings before proposing revisions to the current London classification criteria.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks hormone receptor and Her2 (ERBB2) expression, leaving chemotherapy as the only treatment option. The urgent need for targeted therapy for TNBC patients has led to the investigation of small interfering RNAs (siRNAs), which can target genes in a sequence-specific manner, unlike other drugs. However, the clinical translation of siRNAs has been hindered by the lack of an effective delivery system, except in the case of liver diseases. The MYC oncogene is commonly overexpressed in TNBC compared to other breast cancer subtypes. In this study, we used siRNA to target MYC in MDA-MB-231, MDA-MB-157, MDA-MB-436 and Hs-578T cells. We designed various symmetric and asymmetric (asiRNAs), screened them for in vitro efficacy, modified them for enhanced nuclease resistance and reduced off-target effects, and conjugated them with cholesterol (ChoL) and docosanoic acid (DCA) as a delivery system. DCA was conjugated to the 3’ end of asiRNA by a cleavable phosphodiester linker for in vivo delivery. Our findings demonstrated that asiRNA-VP and Mod_asiRNA10-6 efficiently downregulated MYC and its downstream targets, including RRM2, RAD51 and PARP1. Moreover, in a tumor xenograft model, asiRNA-VP-DCA effectively knocked down MYC mRNA and protein expression. Remarkably, durable knockdown persisted for at least 46 days postdosing in mouse tumor xenografts, with no visible signs of toxicity, underscoring the safety of DCA-conjugated asiRNAs. In conclusion, this study developed novel asiRNAs, design platforms, validated modification patterns, and in vivo, delivery systems specifically targeting MYC in TNBC.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks hormone receptor and Her2 (ERBB2) expression, leaving chemotherapy as the only treatment option. The urgent need for targeted therapy for TNBC patients has led to the investigation of small interfering RNAs (siRNAs), which can target genes in a sequence-specific manner, unlike other drugs. However, the clinical translation of siRNAs has been hindered by the lack of an effective delivery system, except in the case of liver diseases. The MYC oncogene is commonly overexpressed in TNBC compared to other breast cancer subtypes. In this study, we used siRNA to target MYC in MDA-MB-231, MDA-MB-157, MDA-MB-436 and Hs-578T cells. We designed various symmetric and asymmetric (asiRNAs), screened them for in vitro efficacy, modified them for enhanced nuclease resistance and reduced off-target effects, and conjugated them with cholesterol (ChoL) and docosanoic acid (DCA) as a delivery system. DCA was conjugated to the 3’ end of asiRNA by a cleavable phosphodiester linker for in vivo delivery. Our findings demonstrated that asiRNA-VP and Mod_asiRNA10-6 efficiently downregulated MYC and its downstream targets, including RRM2, RAD51 and PARP1. Moreover, in a tumor xenograft model, asiRNA-VP-DCA effectively knocked down MYC mRNA and protein expression. Remarkably, durable knockdown persisted for at least 46 days postdosing in mouse tumor xenografts, with no visible signs of toxicity, underscoring the safety of DCA-conjugated asiRNAs. In conclusion, this study developed novel asiRNAs, design platforms, validated modification patterns, and in vivo, delivery systems specifically targeting MYC in TNBC.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.