Lamin A/C facilitates DNA damage response by modulating ATM signaling and homologous recombination pathways.

Lamin A/C, a core component of the nuclear lamina, forms a mesh-like structure beneath the inner nuclear membrane. While its structural role is well-studied, its involvement in DNA metabolism remains unclear. We conducted sequential protein fractionation to determine the subcellular localization of early DNA damage response (DDR) proteins. Our findings indicate that most DDR proteins, including ATM and the MRE11-RAD50-NBS1 (MRN) complex, are present in the nuclease - and high salt-resistant pellet fraction. Notably, ATM and MRN remain stably associated with these structures throughout the cell cycle, independent of ionizing radiation (IR)-induced DNA damage. Although Lamin A/C interacts with ATM and MRN, its depletion does not disrupt their association with nuclease-resistant structures. However, it impairs the IR-enhanced association of ATM with the nuclear matrix and ATM-mediated DDR signaling, as well as the interaction between ATM and MRN. This disruption impedes the recruitment of MRE11 to damaged DNA and the association of damaged DNA with the nuclear matrix. Additionally, Lamin A/C depletion results in reduced protein levels of CtIP and RAD51, which is mediated by transcriptional regulation. This, in turn, impairs the efficiency of homologous recombination (HR). Our findings indicate that Lamin A/C plays a pivotal role in DNA damage repair (DDR) by orchestrating ATM-mediated signaling, maintaining HR protein levels, and ensuring efficient DNA repair processes.

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.

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.

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.

Epidemiology of Non-Emergent Cancer-Related Emergency Department Visits in Korea between 2016 and 2020.

PURPOSE: As people living with cancer increase in the aging society, cancer-related emergency department (ED) visits are also increasing. This study aimed to investigate the epidemiologic characteristics of non-emergent cancer-related ED visits using a nationwide ED database. MATERIALS AND METHODS: A cross-sectional study was conducted using the National Emergency Department Information System (NEDIS) database. All cancer-related ED visits between 2016 and 2020 were included. The study outcome was non-emergent ED visits, defined as patients triaged into non-emergent condition at both the time of arrival at ED and discharge from ED and were discharged without hospitalization. RESULTS: Among 1185871 cancer-related ED visits over 5 years, 19.0% (n=225491) were classified as non-emergent visits. While abdominal pain and fever are the top chief complaints in both emergent and non-emergent visits, non-emergent visits had high proportions of abdomen distension (4.8%), ascite (2.4%), and pain in lower limb (2.0%) compared with emergent visits. The cancer types with a high proportion of non-emergent visits were thyroid (32.4%) and prostate cancer (30.4%). Adults compared with children or older adults, female, medical aid insurance, urban/rural ED, direct-in compared with transfer-in, and weekend visit were associated with high odds for non-emergent visits. CONCLUSION: Approximately 20% of cancer-related ED visits may be potentially non-emergent. A significant number of non-emergent patients visited the ED due to cancer-related symptoms. To improve the quality of care for people living with cancer, the expansion of supportive care resources besides of ED, including active symptom control, is necessary.

The role of endoscopic ultrasonography for diagnosis of residual rectal neuroendocrine tumor.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for assessing the depth and regional lymph node involvement in rectal neuroendocrine tumors (NETs). However, evidence regarding the effectiveness of EUS in identifying residual lesions in patients with incompletely resected NET is limited. We aimed to evaluate the efficacy of EUS in identifying residual rectal NETs and the clinical outcomes of salvage endoscopic treatment. METHODS: We retrospectively reviewed the records of patients who were transferred to Chosun University Hospital and received salvage treatment for incompletely resected rectal NETs between January 2012 and October 2021. RESULTS: This study included 68 incompletely resected rectal NET, of which 59 were margin-positive and 9 were margin-indeterminate. EUS detection (odds ratio (OR), 8.44; 95% confidence interval (CI), 1.18-41.35) and visual detection (OR, 7.00; 95% CI, 1.50-47.48) were associated with residual lesion in patients with incompletely resected NET. EUS detection of residual lesions showed a sensitivity of 94%, specificity of 71%, positive predictive value of 88%, negative predictive value of 83%, and accuracy of 87%. All patients underwent salvage treatment with band-ligation endoscopic mucosal resection (58.8%) and endoscopic submucosal dissection (41.2%). Residual NETs were diagnosed in 47 of 68 patients (69.1%), and no recurrence was noted during the follow-up period of 51.8 ± 22.9 months. CONCLUSIONS: EUS is a more sensitive method than visual detection for evaluating residual rectal NETs. Salvage endoscopic treatment for incompletely resected NETs is safe and effective.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

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.

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.

Trends in emergency department visits for emergency care-sensitive conditions before and during the COVID-19 pandemic: a nationwide study in Korea, 2019-2021.

OBJECTIVE: Emergency care systems worldwide have been significantly affected by the COVID-19 pandemic. This study investigated the trend of emergency department (ED) visits for emergency care-sensitive conditions (ECSCs) in Korea before and during the pandemic. METHODS: We performed a longitudinal study using the national ED database in Korea from January 2019 to December 2021. We calculated the number and incidence rate of visits for ECSCs per 100,000 ED visits, and the incidence rate ratio of 2021 relative to the value in 2019. The selected ECSCs were intracranial injury, ischemic heart disease, stroke, and cardiac arrest. RESULTS: The number of ED visits for all causes decreased by about 23% during the pandemic. The number of ED visits for intracranial injuries decreased from 166,695 in 2019 to 133,226 in 2020 and then increased to 145,165 in 2021. The number of ED visits for ischemic heart disease and stroke decreased in 2020 but increased to 2019 levels in 2021. In contrast, the number of ED visits for cardiac arrest increased from 23,903 in 2019 to 24,344 in 2020 and to 27,027 in 2021. The incidence rate and incidence rate ratio of these four ECSCs increased from 2019 to 2021, suggesting increasing relative proportions of ECSCs in total ED visits. CONCLUSION: During the COVID-19 pandemic, the number of cardiac arrests seen in the EDs increased, but that of other ECSCs decreased. The decrease in ED visits for ECSCs was not as pronounced as the decrease in ED visits for all causes during the pandemic. Further studies are needed to determine clinical outcomes in patients with ECSC during the pandemic.