Temporal trends in adherence to lifestyle recommendations of patients with hypertension in Korea, 2007-2021.

Adherence to lifestyle recommendations is crucial in managing hypertension, independent of medical treatment. This study aimed to evaluate the implementation of adherence to lifestyle recommendations and analyze the trends in adherence to lifestyle recommendations among patients with hypertension in Korea from 2007 to 2021 using the Korea National Health and Nutrition Examination Survey (KNHANES). The study included adults aged ≥20 years. Factors such as regular physical activity, smoking and alcohol abstinence, weight and stress management, and adherence to a healthy diet were analyzed. In 2021, A doublefold increase was observed in the proportion of patients with hypertension who adhered to sodium restriction compared to 2007. However, 70% of patients with hypertension consume more sodium than recommended. Moreover, potassium intake has steadily decreased since 2014, with only 23.8% of patients with hypertension meeting the recommended intake. The body mass index (BMI) and waist circumference of patients with hypertension have gradually increased, with fewer patients maintaining an appropriate weight. The neglect of diet and weight control among young patients with hypertension who experience high stress levels poses challenges in modifying their lifestyles. Patients with hypertension in Korea still consume high amounts of sodium, whereas potassium intake is gradually decreasing. Additionally, obesity rates have been increasing, especially among young patients with hypertension. A multidisciplinary approach is necessary for improving the lifestyle habits of hypertensive patients.

Acquired Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Resistance of Human Colorectal Cancer Cells Is Linked to Histone Acetylation and Is Synergistically Ameliorated by Combination with HDAC Inhibitors.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for the treatment of various malignancies; however, its therapeutic potential is limited because of the frequent occurrence of tumor cell resistance. In this study, we determined whether TRAIL resistance acquired by repeated administration could be overcome by HDAC inhibition in human colorectal cancer cells. METHODS: TRAIL-resistant HCT116 human colorectal cancer cells (HCT116-TR) were generated by repeated treatment with 10 and 25 ng/mL TRAIL twice weekly for 28 days. RESULTS: The resulting TRAIL-resistant cells were noncross-resistant to other chemotherapeutic agents. The levels of histone acetylation-related proteins, such as ac-histone H4 and HDAC1, were altered in HCT116-TR cells compared with the parental HCT116 cell line. The combined treatment with TRAIL and HDAC inhibitors significantly increased apoptosis in HCT116-TR cells and indicated a synergistic effect. The mechanism by which HDAC inhibition sensitizes HCT116-TR cells to TRAIL is dependent on the intrinsic pathway. In addition, we found that HDAC inhibition enhanced the sensitivity of cells to TRAIL through mitogen-activated protein kinases/CCAAT/enhancer-binding protein homologs of protein-dependent upregulation of death receptor 5. CONCLUSION: These results suggest that histone acetylation is responsible for acquired TRAIL resistance after repeated exposure and acquired resistance to TRAIL may be overcome by combination therapies with HDAC inhibitors.

Risk Factors for Post-Endoscopic Submucosal Dissection Electrocoagulation Syndrome in Patients with Colorectal Neoplasms: A Multicenter, Large-Scale, Retrospective Cohort Study by the Honam Association for the Study of Intestinal Disease (HASID).

Background and Objectives: Colorectal endoscopic submucosal dissection (ESD) is an effective technique for removing colorectal neoplasms with large or cancerous lesions. However, there are few studies on post-ESD electrocoagulation syndrome (PECS), a complication of colorectal ESD. Therefore, this study aimed to investigate the various risk factors for PECS after colorectal ESD. Materials and Methods: We retrospectively analyzed the medical records of 1413 lesions from 1408 patients who underwent colorectal ESD at five tertiary hospitals between January 2015 and December 2020. We investigated the incidence and risk factors associated with PECS. Based on the data, we developed a risk-scoring model to predict the risk of PECS after colorectal ESD. Results: The incidence rate of PECS was 2.6% (37 patients). In multivariate analysis, the use of anti-platelet agents (odds ratio (OR), 2.474; 95% confidence interval (CI), 1.088-5.626; p < 0.031), a lesion larger than 6 cm (OR 3.755; 95% CI, 1.237-11.395; p = 0.028), a deep submucosal invasion (OR 2.579; 95% CI, 1.022-6.507; p = 0.045), and an ESD procedure time ≥ 60 min (OR 2.691; 95% CI, 1.302-5.560; p = 0.008) were independent risk factors of PECS after colorectal ESD. We developed a scoring model for predicting PECS using these four factors. As the score increased, the incidence of PECS also increased, from 1.3% to 16.6%. PECS occurred more frequently in the high-risk group (≥2) (1.8% vs. 12.4%, p < 0.001). Conclusions: In this study, the risk factors for PECS after colorectal ESD were the use of anti-platelet agents, a lesion larger than 6 cm, a deep submucosal invasion, and an ESD procedure time ≥ 60 min. The risk-scoring model developed in this study using these factors could be effective in predicting and preventing PECS.

The Outcomes of Colorectal Endoscopic Submucosal Dissection in Patients with Chronic Kidney Disease: A Honam Association for the Study of Intestinal Disease (HASID) Multicenter Study.

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits.

Outcomes of Colorectal Endoscopic Submucosal Dissection According to the Size of Colorectal Neoplasm: A HASID Multicenter Study.

BACKGROUND/AIM: Endoscopic submucosal dissection (ESD) is a valuable technique for treating colorectal neoplasms. However, there are insufficient data concerning the treatment outcomes in relation to the size of colorectal neoplasms. PATIENTS AND METHODS: The data on ESD for colorectal epithelial neoplasms between January 2015 and December 2020 were retrospectively collected from five tertiary medical centers. Colorectal neoplasms were stratified into groups based on their longitudinal diameter: <20 mm as Group 1, 20-39 mm as Group 2, 40-59 mm as Group 3, and 60 mm or more as Group 4. RESULTS: Of the 1,446 patients, 132 patients were in Group 1 (<20 mm), 1,022 in Group 2 (20-39 mm), 249 in Group 3 (40-59 mm), and 43 in Group 4 (≥60 mm). There was an observed trend of increasing age from Group 1 to Group 4, accompanied by a corresponding increase in the Charlson Comorbidity Index. Procedure time also exhibited a gradual increase from Group 1 to Group 4. Similarly, the length of hospital stay tended to increase from Group 1 to Group 4. The predictive model, using restricted cubic spline curves, revealed that as the size of lesion exceeded 30 mm, complete resection steadily decreased, and major complications notably increased. CONCLUSION: As the size of colorectal neoplasms increases, the rate of complete resection decreases and the rate of complications increases.

Anticoagulants Are a Risk Factor for Delayed Bleeding after Colorectal Endoscopic Submucosal Dissection: A HASID Multicenter Study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3%). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Influence of sleep stages on determining positional dependency in patients with obstructive sleep apnea.

Objective: Supine sleep position and rapid eye movement (REM) stage are widely known to aggravate the severity of obstructive sleep apnea (OSA). In general, position-dependent OSA is defined as an apnea-hypopnea index (AHI) at least twice as high in the supine position as in other sleep positions, but it can be misdiagnosed if a certain sleep stage, REM or NREM, is dominant in a specific sleep position. In this study, we investigated the influences of the sleep stages on positional dependency. Methods: The polysomnographic data from 111 OSA patients aged ≥ 18 years (AHI > five events/hour) who slept in both supine and non-supine positions (each ≥ 5% of the total sleep time) were retrospectively analyzed. The overall ratio of non-supine AHI/supine AHI (NS/S AHI ratio) during the entire sleep was compared between specific sleep stages, i.e., REM or NREM sleep. Additionally, the weighted NS/S AHI ratio reflecting the proportion of each sleep time was created and compared with the original NS/S AHI ratio. Results: The mean value of the NS/S AHI ratio did not differ between the entire sleep and the specific sleep stages. However, those ratios in the individual patients showed poor agreement of the NS/S AHI ratios between the entire sleep and the specific sleep stages. The weighted NS/S AHI ratio also demonstrated poor agreement with the original NS/S AHI ratio, mainly due to the discrepancy in mild to moderate OSA patients. Conclusion: The weighted NS/S AHI ratio might help assess precise positional dependency.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Self-clustered GAN for precipitation nowcasting.

This paper proposes a novel GAN framework with self-clustering approach for precipitation nowcasting (ClusterCast). Previous studies have primarily captured the motion vector using only a single latent space, making the models difficult to adapt to disparate space-time distribution of precipitation. Environmental factors (e.g., regional characteristics and precipitation scale) have an impact on precipitation systems and can cause non-stationary distribution. To tackle this problem, our key idea is to train a generator network to predict future radar frames by learning a sub-network that automatically labels precipitation types from a generative model. The training process consists of (i) clustering the hierarchical features derived from the generator stem using a sub-network and (ii) predicting future radar frames according to the self-supervised labels, enabling heterogeneous latent representation. Additionally, we attempt an ensemble forecast that prescribes random perturbations to improve performance. With the flexibility of representation learning, ClusterCast enables the model to learn precipitation distribution more accurately. Results indicate that our method generates non-blurry future frames by preventing mode collapse, and the proposed method demonstrates robustness across various precipitation scenarios. Extensive experiments demonstrate that our method outperforms four benchmarks on a 2-h prediction basis with a mean squared error (MSE) of 8.9% on unseen datasets.

Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Long-Term Tumor-Targeting Effect of E. coli as a Drug Delivery System.

To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary amine group of a cell membrane protein. In addition, positron emission tomography (PET) is a representative non-invasive imaging technology and is actively used in the field of drug delivery along with radioisotopes capable of long-term tracking, such as zirconium-89 (89Zr). The membrane proteins were labeled with 89Zr using chelate (DFO), and not only was the long-term biodistribution in tumors and major organs evaluated in the body, but the labeling stability of 89Zr conjugated to the membrane proteins was also evaluated through continuous tracking. E. coli accumulated at high levels in the tumor within 5 min (initial time) after tail intravenous injection, and when observed after 6 days, 89Zr-DFO on the surface of E. coli was found to be stable for a long period of time in the body. In this study, we demonstrated the long-term biodistribution and tumor-targeting effect of an E. coli-based drug delivery system and verified the in vivo stability of radioisotopes labeled on the surface of E. coli.

Comparison of Neutralizing Activity between Vaccinated and Unvaccinated Hospitalized COVID-19 Patients Infected with Delta, Omicron BA.1, or Omicron BA.2 Variant.

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.