Background: Fusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNAseq) compared with that of conventional diagnostics in patients with acute leukemia. Methods: We retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics. Results: RNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel (KMT2A::THAP12 , RUNX1::PRPF19 , MLLT10::UBE2L6, and FUS::ZNF362) and three rare (HNRNPH1::ERG, RUNX1::USP42, and ETV6::NCOA2) fusions. Conclusions This was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

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.

Purpose: Hereditary spastic paraplegia (HSP) refers to a group of genetic neurodegenerative diseases marked by gradually worsening spasticity and hyperreflexia in the lower extremities. This study aimed to describe the clinical and genetic characteristics of Korean patients with spastic paraplegia. Materials and Methods: We retrospectively reviewed medical records of 69 patients with spastic paraplegia from 54 unrelated families between 2002 and 2024. Genetic, clinical, electrophysiological, and radiological features were comprehensively analyzed. Results: Causative genes were identified in 34 (63%) of 54 unrelated families; SPAST, detected in 26 families, was the most prevalent. Seven novel pathogenic variants were identified. Clinically, the median age of symptom onset was 25 years [14.0–37.0]. Out of 69 patients with spastic paraplegia, 51 (74%) presented with the pure form of spastic paraplegia, which included all patients with SPG4. Spastic gait was a universal feature in all patients. Urinary dysfunction was present in 42 (61%) patients. Additional neurologic manifestations included peripheral neuropathy 9 (13%), cognitive impairment 5 (7%), upper limb weakness 4 (6%), dysarthria 4 (6%), dysphagia 3 (4%), ataxia 3 (4%), and scoliosis 1 (3%). Brain MRI findings demonstrated a thin corpus callosum in two patients with SPG11; all patients with SPG4 had normal findings. Spine MRI revealed spinal cord atrophy in 16 (27%) patients, including 6 (21%) patients with SPG4. Conclusion The study comprehensively reviewed genetic and clinical spectra of spastic paraplegia in Korean patients, emphasizing the predominance of SPAST as the causative gene and underscoring the genetic and phenotypic heterogeneity of spastic paraplegia.

The global shortage of healthcare personnel, especially in low- and middle-income countries, has raised concerns about the quality and availability of medical education across these economies. Therefore, standardization and accreditation of medical education are essential to ensure the competence of healthcare professionals. This study reports the first-ever application of the set of standards developed by the Korean Institute of Medical Education and Evaluation (KIMEE) to assess a Vietnamese medical school. Under this initiative, the Accreditation Standards of KIMEE 2019 (ASK 2019) was implemented under the auspices of a Korea International Cooperation Agency Development Project. This study compared the evaluation results of a Vietnamese medical school’s performance with that of accredited Korean medical schools. The findings revealed both strengths and areas requiring significant improvement and underscore the need for Vietnam to develop its own contextually appropriate accreditation system.

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: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.