Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Legal risks and liability issues in medical practice serve as a primary catalyst for the current collapse of essential healthcare services in Korea. Currently, medical disputes in Korea are disproportionately focused on criminal prosecutions and high-damages civil litigation. This punitive approach fosters a culture of concealment, encourages defensive medicine, and accelerates the exodus of medical professionals from essential fields. Ultimately, this cycle deprives the system of opportunities for improvement and poses a significant threat to patient safety. In contrast, many advanced nations have adopted principles of “Just Culture” and “Safe Space,” prioritizing non-punitive reporting and systemic root-cause analysis over individual retribution. To address these issues, this paper proposes four key strategies: First, the establishment of an independent “Patient Safety Investigation Agency” to objectively investigate incidents and identify systemic flaws. Second, a transition from criminal punishment to licensing board-led management, focusing on re-education and counseling to maintain quality of care. Third, the enactment of “Apology Laws” to ensure that expressions of regret or apologies cannot be used as legal evidence of liability, thereby fostering trust and psychological recovery. Finally, the creation of a “Patient Safety Fund” to provide prompt and sufficient public compensation to victims regardless of proven negligence. In conclusion, it is imperative to shift the paradigm by defining medical accidents as “system failures” rather than individual faults. Strengthening the social safety net will encourage medical professionals to return to essential care and build a sustainable healthcare environment centered on patient safety.

Objective: To evaluate the performance of supplemental automated breast ultrasound (ABUS) added to mammography-based breast cancer screening for women with nondense breasts. Materials and Methods: A retrospective search of radiology databases at two tertiary institutions identified asymptomatic women with nondense breasts who underwent breast cancer screening using both digital mammography (DM) and supplemental ABUS between January 2020 and December 2023. We excluded women without sufficient follow-up data or those without an established final diagnosis, including histopathologic results. The performance measures of DM alone and ABUS combined with DM (ABUS plus DM) were compared. The primary outcome was the cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed for women with scattered fibroglandular density and almost entirely fatty breasts. Results: A total of 2,904 pairs of screening examinations were performed in 1,683 women (59 ± 10 years), detecting 26 cancers. In comparison with DM alone, ABUS plus DM showed higher CDR (9.0 vs. 7.9 per 1,000 examinations, P < 0.001), higher sensitivity (100% [26/26] vs. 88.5% [23/26], P < 0.001), and lower specificity (95.0% [2,735/2,878] vs. 97.9% [2,817/2,878], P < 0.001). In women with scattered fibroglandular density, ABUS increased the CDR from 7.4 to 8.5 per 1,000 examinations and improved the sensitivity from 87.0% [20/23] to 100% [23/23] (P < 0.001). In women with almost entirely fatty breasts, ABUS plus DM showed the same CDR (16.4 per 1,000 examinations) and sensitivity (100% [3/3]) as DM alone. Three cancers (11.5% [3/26]), all of which were stage T1N0, were detected only by supplemental ABUS. Conclusion Supplemental ABUS improved cancer detection and sensitivity in women with nondense breasts, with the benefits primarily observed in those with scattered fibroglandular density.

Background: Menopausal status can increase the risk of cardiocerebrovascular diseases (CCVDs) in women with type 2 diabetes mellitus (T2DM). Regular exercise is well-known to reduce this risk. This study explored the impact of exercise on CCVD and mortality in women with T2DM according to their menopausal status. Methods: A total of 32,477 premenopausal and 53,690 postmenopausal Korean women with T2DM aged 40 to 60 years from a national health examination cohort (2009 to 2018) were included. We evaluated risks for stroke, myocardial infarction (MI), and mortality based on exercise intensity. Cox proportional hazard regression analyses were performed to obtain the adjusted hazard ratio (aHR) and 95% confidence interval. Results: Exercise reduced stroke, MI, and mortality risks in women with T2DM, regardless of menopausal status. The highest effects of aHR compared to the sedentary group were 0.68 for stroke, 0.66 for MI, and 0.81 for mortality. Postmenopausal women experienced significant MI risk reductions at most exercise intensities, with the greatest reduction in the ≥1,500 metabolic equivalent of task score group unlike premenopausal women. However, stroke and mortality risk reductions in postmenopausal women were less pronounced compared to premenopausal women. Conclusion Exercise reduces CCVD risk in women with T2DM across menopausal status. Postmenopausal women with T2DM had more benefits from exercise on MI but fewer benefits on stroke and mortality than premenopausal women. In premenopausal women with T2DM, exercise was not associated with a lower MI risk.

Background: The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk. Methods: Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates. Results: During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442). Conclusion Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.