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.

Purpose: This study explored the experiences of physicians and nurses providing end-oflife care in Korean acute care hospitals. It aimed to identify the challenges faced in caring for dying patients and to suggest strategies for improving hospital-based end-of-life care. Methods: A qualitative exploratory design was employed using focus group interviews.Eleven healthcare professionals (five physicians and six nurses) working in tertiary or general hospitals participated in the study between July and August 2018. The interviews were conducted using a semi-structured guide covering seven thematic areas. All sessions were audio-recorded, transcribed verbatim, and analyzed thematically following Braun and Clarke’s framework. Results: Six major themes emerged: (1) communication with patients and families, (2) physical care for dying patients, (3) psychological and spiritual support, (4) hospital environment and system constraints, (5) moral distress and emotional burden on healthcare providers, and (6) suggestions for improvement. The participants described difficulties in open communication, limited resources for comfort care, emotional strain from invasive treatment at the end of life, and the absence of standardized institutional protocols.They emphasized the need for structured communication training, multidisciplinary collaboration, and integration of palliative care principles into acute care practice. Conclusion Physicians and nurses play a pivotal yet emotionally demanding role in providing end-oflife care in acute hospitals. Institutional reforms, including education, protocol development, and supportive environments, are essential to ensuring dignified, patient-centered care and sustain healthcare providers in their professional roles.

Older adults are potential beneficiaries of digital health technologies but remain vulnerable to the digital divide. This study aimed to compare digital accessibility, perceptions, and intention to use digital healthcare services among urban and rural older adults, and to identify associated factors. Methods: A cross-sectional descriptive study was conducted with 140 community-dwelling older adults aged 65 and above in urban and rural areas. Data were collected using structured questionnaires covering digital device ownership, usage patterns, perceived ease of use, digital self-efficacy, and perceptions of digital healthcare—assessed in four dimensions: expectations, concerns, emotional responses, and perceived necessity. Statistical analyses included t-tests, chi-square tests, and binary logistic regression. Results: Urban older adults had higher ownership and usage rates of smartphones (χ2=5.78, p=.016) and the internet (χ2=18.53, p<.001), and significantly more experience with digital device education compared to rural older adults (χ2=5.85, p=.016). While no significant differences were found in expectations, concerns, and emotional responses, rural participants showed significantly higher perceived necessity (t=-2.30, p=.023). The overall intention to use digital healthcare services was high in both groups, and binary logistic regression analysis revealed that expectations (odds ratio [OR]=1.78, 95% confidence interval [CI]=1.10~2.89, p=.019) and perceived necessity (OR=2.24, 95% CI=1.39~3.60, p=.001) were significant predictors of intention to use. Conclusion: Promoting digital healthcare adoption among older adults requires enhancing individual expectations and perceived needs beyond simply providing technology. In rural areas, strategies should focus on improving digital accessibility and offering tailored education programs.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

BACKGROUND/OBJECTIVES: Supplementation of nicotinamide adenine dinucleotide (NAD) precursors has been investigated for its potential to counteract age-related physiological decline. While decreased NAD + level is associated with conditions such as obesity and dyslipidemia, few studies have explored its metabolic impact in relatively young animals.Here, we hypothesized that nicotinamide mononucleotide (NMN) could alleviate highfat diet-induced metabolic stress in young mice and sought to elucidate the underlying mechanisms.MATERIALS/METHODS: We first conducted a secondary analysis of hepatic transcriptome datasets from multiple NMN intervention studies to identify target pathways. Next, 11-weekold lean and obese C57BL/6N mice administrated NMN (500 mg/kg/day) for 1 mon were analyzed for metabolic parameters and gene expression for the target pathways. In vitro study using AML12 cell line was then conducted to confirm the effects of NMN. Additionally, transcriptomic data from liver-specific nicotinamide phosphoribosyltransferase (NAMPT)-deficient mice were analyzed to examine the relationship between NAD + metabolism, endoplasmic reticulum (ER) stress, and circadian rhythm. RESULTS: The secondary analysis of hepatic transcriptome datasets revealed potential target pathways related to circadian regulation and hepatic ER stress. In mouse study, short-term NMN administration significantly decreased body weight and fat mass. NMN also alleviated hepatic ER stress response in vivo and in vitro. Additional analysis revealed that the mice with diet-induced metabolic stress or NAMPT deficiency led to phase shifts of the hepatic circadian core clock oscillation by advancing the peak time, while time-restricted feeding shifted the opposite, indicating the metabolic regulation of the circadian phase. CONCLUSION Short-term NMN administration effectively attenuated obese condition in young mice and mitigated hepatic ER stress. The altered ER stress was regulated by NAMPT, potentially through the phase shift of the hepatic circadian rhythm.

Background: To investigate the fracture risks associated with anti-diabetic drugs in older women with type 2 diabetes mellitus (T2DM), who are particularly susceptible to skeletal fragility. Methods: Using data from the Korean National Health Insurance Service, this nested case-control study included 10,104 older women with T2DM and osteoporotic fractures (aged 66.5±3.4 years) matched in a 1:3 ratio with controls by birthdate, Charlson Comorbidity Index, and cohort entry date. We analyzed the odds of major osteoporotic fracture (MOF), vertebral fracture (VF), and non-VF (NVF) in users of sulfonylurea, thiazolidinedione (TZD), dipeptidyl peptidase-4 inhibitor, and sodium-glucose cotransporter 2 inhibitor (SGLT2i), compared to metformin (Met)-only users using multivariable logistic regression. Results: During a follow-up period of 3.8±2.8 years, TZD users had a higher risk of MOF than Met-only users (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.19-1.53; P<0.001). Risks of VF and NVF were also increased in the TZD group (OR, 1.21; 95% CI 1.03-1.42; P=0.022 and OR, 1.32; 95% CI 1.14-1.52; P<0.001, respectively). No significant differences were observed in other drug groups. The increased risk of VF and NVF in the TZD group were particularly pronounced in patients with normal or osteopenic bone mineral density (BMD) and in those with normal body mass index (BMI), respectively. Conclusions In older women with T2DM, TZD use was associated with increased VF and NVF risks, particularly among those with normal or osteopenic BMD and normal BMI. SGLT2i showed no increased risk, but further large-scale studies are needed to confirm its skeletal safety.

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a complication of antiresorptive therapy, including bisphosphonates and denosumab. Although bone scintigraphy (BS) detects early metabolic changes, its diagnostic role in MRONJ and its role in assessing systemic skeletal involvement remain unclear. This study analyzed BS tracer uptake patterns and their association with MRONJ severity and clinical variables. Materials and Methods: This retrospective study analyzed 319 patients diagnosed with MRONJ from 2010 to 2019. Three-phase BS, cone-beam computed tomography (CBCT), and clinical data were reviewed. Tracer uptake intensity in the jaw was visually graded, and extra-jaw skeletal uptake was categorized by region and number of involved sites. Associations between the MRONJ stage, jaw uptake intensity, and skeletal uptake beyond the jaw were analyzed. Results: Higher tracer uptake intensity in the jaw was associated with advanced MRONJ stages (P<0.001), particularly Stage 3. However, the number of skeletal sites beyond the jaw did not correlate with the MRONJ stage (P=0.512).Distribution of local and systemic tracer uptake in body patterns across MRONJ Stages did not show statistical significance. Conclusion Elevated tracer uptake in the jaw correlates with advanced MRONJ stages and broader skeletal tracer uptake, suggesting a potential link between local disease severity and systemic skeletal involvement. However, skeletal uptake beyond the jaw does not independently predict the MRONJ stage, suggesting that systemic bone involvement alone may not reflect increased disease severity.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Objectives: This study aimed to investigate the clinical characteristics, treatment outcomes, and factors influencing treatment success in patients with denosumab (Dmab)-related osteonecrosis of the jaw (DRONJ). Patients and Methods: This retrospective cohort study included the patients who were diagnosed with DRONJ and treated at the authors’ affiliated hospital, between August 2019 and August 2024. The patients were divided into the three groups; Group 1, low-dose Dmab; Group 2, transition from bisphosphonates (BPs) to low-dose Dmab; Group 3, high-dose Dmab. Differences in clinical characteristics among the groups were compared. Surgical outcomes were classified into three categories: complete healing, partial healing, and no healing. “Treatment success” was defined as the combined proportion of complete and partial healing. Results: A total of 178 DRONJ patients were included in this study. Most of DRONJ occurred in osteoporosis patients. In patients treated with lowdose Dmab, prior BP use resulted in the development of MRONJ within a shorter period after Dmab administration but did not affect disease severity or treatment outcomes. Overall postoperative healing outcomes were favorable at 3 months after DRONJ treatment. The overall treatment success rate was 81.5%; Group 1, 85.0%; Group 2, 82.8%; Group 3, 53.8%, P=0.027). Multiple regression analysis demonstrated that Dmab dosage was a significant factor influencing treatment success, whereas age, treatment duration, lesion location, and DRONJ stage were not (odds ratio, 5.13; 95% confidence interval, 1.19-22.14; P=0.028). Conclusion The earlier onset in the BP to Dmab transition group may be attributable to the cumulative duration of antiresorptive therapy. Patients treated with high-dose Dmab demonstrated poorer prognosis and more frequent recurrence after MRONJ treatment compared with those treated with low-dose Dmab or BP to Dmab transition therapy. herefore, these findings need to be considered for treatment of DRONJ.

Background: The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT. Methods: We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression. Results: Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03). Conclusions In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.