Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

Background/Aims: Chronic kidney disease (CKD) is a significant health problem worldwide, and identifying risk factors for CKD is crucial. We investigated the association between steatotic liver disease (SLD) and the incidence of CKD. Methods: This longitudinal cohort study involved 70,361 adults who did not have CKD at baseline and who underwent at least two health checkups. SLD status was assessed via ultrasonography. The severity of SLD was determined using the Fibrosis-4 score. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2 . Results: Over 475,835 person-years (mean 6.8 years), 2,723 participants developed CKD.The adjusted hazard ratio (aHR) for development of CKD in participants with SLD compared to those without SLD was 1.17 (95% confidence interval [CI], 1.08 to 1.27), with the risk increasing with SLD severity. The aHR (95% CI) for incident CKD was 0.84 (0.51 to 1.37) for cryptogenic SLD, 1.25 (1.16 to 1.36) for metabolic dysfunction-associated SLD (MASLD), and 1.32 (1.01 to 1.73) for metabolic dysfunction-associated alcoholic liver disease (MetALD) compared with participants without SLD. Within these SLD subclassifications, the risk of CKD development was increased as disease severity advanced. Conclusions SLD was linked to a higher incidence of CKD, with the CKD risk increasing sequentially from cryptogenic SLD to MASLD and MetALD. Advanced fibrosis in each SLD subclassification further increases the risk of CKD. Stratifying SLD according to metabolic dysfunction, significant alcohol intake, and fibrosis severity may help identify and monitor individuals at high risk of developing CKD.

Background: Emergency department (ED) overcrowding poses a global challenge, particularly for critically ill patients requiring intensive care unit (ICU) admission. Although delays in ICU transfer increase mortality in critically ill populations, the optimal timing for septic shock remains uncertain. Methods: We conducted a target trial emulation using a prospective cohort of 815 septic shock patients from 19 Korean hospitals. Delayed ICU transfer was defined using restricted cubic splines. The primary outcome was in-hospital mortality. Multivariable logistic regression and inverse probability treatment weighting were used to adjust for confounders of age, sex, comorbidities, severity of illness, and mechanical ventilation use. Subgroup analyses were performed to assess the effect across patient characteristics. Results: The median time of ED-to-ICU transfer was 6.7 hours (interquartile range, 4.7–11.4), and only 7% of patients were transferred within 3 hours. ICU transfer within 3 hours was associated with significantly lower in-hospital mortality (odds ratio, 0.48; 95% CI, 0.24–0.94) compared to later transfers. Mortality risk increased with elapsing time up to 6 hours and then plateaued. The benefit of early ICU transfer was consistent across subgroups but was particularly pronounced in patients requiring extracorporeal membrane oxygenation or continuous renal replacement therapy (P for interaction=0.02). Conclusions Early ICU transfer within 3 hours significantly reduces mortality in patients with septic shock, with the greatest benefit observed in those requiring advanced organ support. These findings highlight the need for system-wide strategies to reduce ED boarding time and prioritize timely ICU admission for septic shock management.

Objective: To investigate the incidence and risk factors of cardiovascular disease (CVD) in adolescent and young adult survivors of cervical cancer. Methods: This retrospective cohort study used data from the Korean National Health Insurance Service. Adolescent and young adult (AYA) cervical cancer survivors (n=7,803) were matched with non-cancer controls (n=23,327) using 1:3 propensity score matching, and hazard ratios (HRs) for CVD were determined using Cox regression models. Multivariable Cox regressions were used to assess CVD incidence according to cancer treatment and identify risk factors. Results: A total of 7,803 AYA survivors with cervical cancer were analyzed in this study during a median 8.9 years of follow-up. They developed any CVD with an adjusted HR of 1.47 (95% confidence interval [CI]=1.33–1.62) compared with the non-cancer controls. Those who underwent concurrent chemoradiotherapy had markedly elevated risks of heart failure (subHR=2.66; 95% CI=1.24–5.72), ischemic heart disease (subHR=1.78, 95% CI=1.11–2.86), deep vein thrombosis (subHR=15.32; 95% CI=9.16–25.63), and pulmonary embolism (subHR=14.99; 95% CI=6.31–35.62). Diabetes, hypertension and chemoradiation therapy were identified as potential risk factors that increase the risk of CVD by 1.55-fold, 1.62-fold and 2.64-fold, respectively. Conclusion These findings indicate a need to pay increased attention to cardiovascular health management in adolescent and young adult cervical cancer survivors, particularly those treated with chemoradiotherapy.

Purpose: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. Materials and Methods: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. Results: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. Conclusion In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Background: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using realworld data. Methods: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. Results: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88–1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62–0.97; P = 0.024). Conclusion As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71–0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73–0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Purpose: Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. Materials and Methods: Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. Results: From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. Conclusion We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Purpose: The purpose of the study was to validate the Korean version of Cancer Survivors’ Unmet Needs (CaSUN) scale among non–small cell lung cancer survivors. Materials and Methods: Participants were recruited from outpatient clinics at the Samsung Medical Center in Seoul, South Korea, from January to October 2020. Participants completed a survey questionnaire that included the CaSUN. Exploratory and confirmatory factor analysis and Pearson’s correlations were used to evaluate the reliability and validity of the Korean version of the CaSUN (CaSUN-K). We also tested known-group validity using an independent t test or ANOVA. Results: In total, 949 provided informed consent and all of which completed the questionnaire. Among the 949 patients, 529 (55.7%) were male; the mean age and median time since the end of active treatment (standard deviation) was 63.4±8.8 years and the median was 18 months. Although the factor loadings were different from those for the original scale, the Cronbach’s alpha coefficients of the six domains in the CaSUN-K ranged from 0.68 to 0.95, indicating satisfactory internal consistency. In the CFA, the goodness-of-fit indices for the CaSUN-K were high. Moderate correlations demonstrated the convergent validity of CaSUN-K with the relevant questionnaire. More than 60% of the participants reported information-related unmet needs, and the CaSUN-K discriminated between the needs reported by the different subgroups that we analyzed. Conclusion The CaSUN-K is a reliable and valid measure for assessing the unmet needs in a cancer population, thus this tool help population to receive timely, targeted, and relevant care.

Background/Aims: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. Methods: Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebogroup (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. Results: Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological wellbeing (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. Conclusions The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.