Background: and Purpose: Dementia, particularly Alzheimer’s disease, is a significant global health concern, with early diagnosis and treatment development being critical goals. While numerous cohorts have advanced dementia research, there is a lack of comprehensive data on ethnic differences, particularly for the Korean population. The Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) aims to establish a large-scale, hospital-based dementia cohort to address this gap, with a focus on understanding disease progression, developing early diagnostics, and supporting treatment advancements specific to the Korean population. Methods: K-ROAD comprises multiple prospective cohorts. Participants underwent clinical evaluations, neuroimaging, and biomarker analysis, with data collected on a range of clinical and genomic markers. Results: As of December 2023, K-ROAD has recruited over 5,800 participants, including individuals across the Alzheimer’s clinical syndrome, subcortical vascular cognitive impairment, and frontotemporal dementia spectra. Preliminary findings highlight significant ethnic differences in amyloid positivity, cognitive decline, and biomarker profiles, compared to Western cohorts. Conclusions The K-ROAD cohort offers a unique and critical resource for dementia research, providing insights into ethnic-specific disease characteristics and biomarker profiles. These findings will contribute to the development of personalized diagnostic and therapeutic approaches to dementia, enhancing global understanding of the disease.

Background: and Purpose: Dementia, particularly Alzheimer’s disease, is a significant global health concern, with early diagnosis and treatment development being critical goals. While numerous cohorts have advanced dementia research, there is a lack of comprehensive data on ethnic differences, particularly for the Korean population. The Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) aims to establish a large-scale, hospital-based dementia cohort to address this gap, with a focus on understanding disease progression, developing early diagnostics, and supporting treatment advancements specific to the Korean population. Methods: K-ROAD comprises multiple prospective cohorts. Participants underwent clinical evaluations, neuroimaging, and biomarker analysis, with data collected on a range of clinical and genomic markers. Results: As of December 2023, K-ROAD has recruited over 5,800 participants, including individuals across the Alzheimer’s clinical syndrome, subcortical vascular cognitive impairment, and frontotemporal dementia spectra. Preliminary findings highlight significant ethnic differences in amyloid positivity, cognitive decline, and biomarker profiles, compared to Western cohorts. Conclusions The K-ROAD cohort offers a unique and critical resource for dementia research, providing insights into ethnic-specific disease characteristics and biomarker profiles. These findings will contribute to the development of personalized diagnostic and therapeutic approaches to dementia, enhancing global understanding of the disease.

Background: and Purpose: Dementia, particularly Alzheimer’s disease, is a significant global health concern, with early diagnosis and treatment development being critical goals. While numerous cohorts have advanced dementia research, there is a lack of comprehensive data on ethnic differences, particularly for the Korean population. The Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) aims to establish a large-scale, hospital-based dementia cohort to address this gap, with a focus on understanding disease progression, developing early diagnostics, and supporting treatment advancements specific to the Korean population. Methods: K-ROAD comprises multiple prospective cohorts. Participants underwent clinical evaluations, neuroimaging, and biomarker analysis, with data collected on a range of clinical and genomic markers. Results: As of December 2023, K-ROAD has recruited over 5,800 participants, including individuals across the Alzheimer’s clinical syndrome, subcortical vascular cognitive impairment, and frontotemporal dementia spectra. Preliminary findings highlight significant ethnic differences in amyloid positivity, cognitive decline, and biomarker profiles, compared to Western cohorts. Conclusions The K-ROAD cohort offers a unique and critical resource for dementia research, providing insights into ethnic-specific disease characteristics and biomarker profiles. These findings will contribute to the development of personalized diagnostic and therapeutic approaches to dementia, enhancing global understanding of the disease.

Background: and Purpose: Dementia, particularly Alzheimer’s disease, is a significant global health concern, with early diagnosis and treatment development being critical goals. While numerous cohorts have advanced dementia research, there is a lack of comprehensive data on ethnic differences, particularly for the Korean population. The Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) aims to establish a large-scale, hospital-based dementia cohort to address this gap, with a focus on understanding disease progression, developing early diagnostics, and supporting treatment advancements specific to the Korean population. Methods: K-ROAD comprises multiple prospective cohorts. Participants underwent clinical evaluations, neuroimaging, and biomarker analysis, with data collected on a range of clinical and genomic markers. Results: As of December 2023, K-ROAD has recruited over 5,800 participants, including individuals across the Alzheimer’s clinical syndrome, subcortical vascular cognitive impairment, and frontotemporal dementia spectra. Preliminary findings highlight significant ethnic differences in amyloid positivity, cognitive decline, and biomarker profiles, compared to Western cohorts. Conclusions The K-ROAD cohort offers a unique and critical resource for dementia research, providing insights into ethnic-specific disease characteristics and biomarker profiles. These findings will contribute to the development of personalized diagnostic and therapeutic approaches to dementia, enhancing global understanding of the disease.

Purpose: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Materials and Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). Conclusion The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Background: We aimed to analyze the impact of concomitant Maze procedure on the clinical and rhythm outcomes, and echocardiographic parameters in tricuspid repair for patients with severe tricuspid regurgitation (TR) and persistent atrial fibrillation (AF). Methods: Patients who had severe TR and persistent AF and underwent tricuspid valve (TV) repair were included in the study. Both primary TR and secondary TR were included in the current study. The study population was stratified according to Maze procedure. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE) at 15 years postsurgery. Propensity-score matching analyses was performed to adjust baseline differences. Results: Three hundred seventy-one patients who underwent tricuspid repair for severe TR and persistent AF from 1994 to 2021 were included, and 198 patients (53.4%) underwent concomitant Maze procedure. The maze group showed 10-year sinus rhythm (SR) restoration rate of 55%. In the matched cohort, the maze group showed a lower cumulative incidence of cardiac death (4.6% vs. 14.4%, P = 0.131), readmission for heart failure (8.1% vs. 22.2%, P = 0.073), and MACCE (21.1% vs. 42.1%, P = 0.029) at 15 years compared to the non-maze group. Left atrial (LA) diameter significantly decreased in the maze group at 5 years (53.3 vs. 59.6 mm, P < 0.001) after surgery compared to preoperative level, and there was a significant difference in the change of LA diameter over time between the two groups (P = 0.013). Conclusion The Maze procedure during TV repair in patients with severe TR and persistent AF showed acceptable SR rates and lower MACCE rates compared to those without the procedure, while also promoting LA reverse remodeling.

Background and Objectives: Early diastolic mitral annular tissue (e’) velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e’ velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively.According to the current guidelines, the cut-off value of e’ velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e’ velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634–0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477–0.998;p=0.049). Abnormal e’ velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170–5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189–21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e’ velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308– 0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680–1.356; p<0.001). Conclusions In patients aged <65 years with primary MR, e’ velocity served as an independent predictor of all-cause and cardiovascular deaths.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Background and Objectives: The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. Methods: We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). Results: RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. Conclusions RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.