Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

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.

The Wikstroemia genus is highly regarded in traditional Asian medicine for its diverse therapeutic applications, including the treatment of inflammatory and infectious conditions. Among its members,Wikstroemia trichotoma (Thunb.) Makino remains a promising medicinal resource which is yet to be chemicallycharacterized. To ensure the chemical consistency of W. trichotoma, we developed and validated the first HPLC method for the simultaneous quantification of three major marker compounds: chlorogenic acid (1), miconioside B (2), and matteucinol 7-O-apiofuranosyl(1→6)-glucopyranoside (3). Chromatographic separation was achieved on a C18 column using a gradient elution system of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection was optimized using a photodiode array (PDA) detector at 280 and 325 nm, based on the absorption maxima of the markers. The method was validated in accordance with the International Council for Harmonisation (ICH) and the Ministry of Food and Drug Safety (MFDS) guidelines. The results demonstrated high linearity (r2 > 0.999), with limits of detection and quantitation ranging from 4.28–6.42 and 12.97–19.47 μg/ mL, respectively. Intra- and inter-day precision (% RSD ≤ 1.83%) and accuracy (recoveries of 92.5–101.7%) were within acceptable limits. Quantitative analysis revealed the contents of 1, 2, and 3 in the W. trichotoma extract to be 19.9, 139.8, and 264.9 mg/g, respectively. This study provides a reliable analytical framework for the standardization, quality control, and future pharmacological evaluation of W. trichotoma.

Purpose: Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses. Materials and Methods: This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared. Results: Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction. Conclusion Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

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.

Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

Objectives: Sleep apnea surgery is effective only in appropriately selected patients, making accurate identification of candidates essential. This study aimed to introduce a novel anatomical index for identifying patients most likely to achieve favorable surgical outcomes. Methods: A retrospective review was performed on patients with obstructive sleep apnea who underwent multilevel surgery by a single surgeon at a tertiary medical center between 2012 and 2021. Anatomical parameters, endoscopic images, and pre- and postoperative polysomnography findings were analyzed. Some patients exhibited posterior pillar hypertrophy (PPH), characterized by thickening of the palatopharyngeal muscle beyond normal dimensions. To evaluate the exclusive effects of PPH, patients were randomly selected and subjected to propensity score matching. Results: Logistic regression analysis identified tonsil grade, body mass index, and posterior pillar thickness as significant predictors of surgical success. Success rates differed significantly between the PPH(+) and PPH(−) groups, with 51.9% success in the PPH(+) group compared to 40.7% in the PPH(−) group. Moreover, the PPH(+) group demonstrated a significantly greater postoperative improvement in both the apnea–hypopnea index and oxygen desaturation index. Conclusion The presence of PPH represents an important anatomical predictor of surgical success in the treatment of obstructive sleep apnea. This index facilitates more precise patient selection and surgical planning, potentially improving overall treatment outcomes.

Background: Human muscle satellite (stem) cells (MuSCs) are essential for investigating muscle physiology, regeneration, and disease mechanisms. Primary cultures derived directly from human tissues offer a more physiologically relevant model than immortalized cell lines. However, the isolation and characterization of MuSCs from human upper limb tissues are limited. Therefore, this study aimed to establish and characterize a primary culture system for MuSCs obtained from human upper limb muscle tissue. Methods: Human muscle tissues were obtained from upper limb surgical specimens. Muscle samples were mechanically and enzymatically dissociated to isolate muscle-derived cells, which were cultured under standard growth conditions. Cell morphology and proliferation were monitored during the culture period. Myogenic characteristics were assessed by examining the expression of muscle-specific markers including myogenic regulatory factors and structural proteins. Additionally, myogenic differentiation capacity was evaluated by inducing differentiation and analyzing the formation of multinucleated myotubes. Results: Primary MuSCs were isolated from human upper limb tissues and expanded in vitro. The cultured cells exhibited a typical spindle-shaped morphology and demonstrated significant proliferative capacity. Characterization confirmed the expression of myogenic markers, indicating the presence of muscle-derived precursor cells. Following induction of differentiation, the cells formed multinucleated myotube-like structures and expressed muscle proteins associated with differentiation, highlighting their potential for myogenic differentiation. Conclusion This study established a reliable protocol for isolating and culturing MuSCs from human upper limb tissues. Cultured cells displayed typical myogenic characteristics and differentiation capacity, indicating that this model could be a valuable platform for studying human muscle biology and potential therapeutic applications.

Background and Objectives: Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort. Methods: The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs). Results: Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective. Conclusions Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.