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.

Background: Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal dystrophies. The genetic landscape of RP has been characterized; however, knowledge gaps regarding age-specific genetic variation trends in Korean patients remain. We comprehensively characterized the age-stratified genetic landscape of RP in Korean patients, with a focus on identifying novel mutational trends and clinically actionable insights. Methods: We performed targeted next-generation sequencing of 199 genes associated with RP and related disorders in a cohort of 403 unrelated patients clinically diagnosed as having RP. We analyzed the inheritance patterns, variation spectrum, and prevalence of pathogenic variants, stratifying the results by age, and conducted copy number variation (CNV) analysis. Results: A genetic diagnosis was achieved for 193 of the 403 patients (48%). The diagnostic yield was highest in patients diagnosed before 20 yrs of age (60%), with lower yields in older age groups. Although USH2A and EYS, the most common causative genes in autosomal recessive inheritance, were frequently identified, RPGR pathogenic variants accounted for a significantly larger proportion of genetically solved cases diagnosed before the age of 20 yrs (27%–28%) than in those with later-onset disease (9%–15%). CNVs were identified in 4% of genetically solved cases. Conclusions The results underscore distinct, age-related genetic contributions to RP in Korean patients, with RPGR variants demonstrating relevance in early-onset disease, and provide diagnostic insights to improve current practices. These findings can aid in prioritizing gene therapy targets and refining screening strategies.

Background: We compared the immunoglobulin (IG) heavy chain (IGH) leader and FR1 primer sets to measure clone sizes and detect immunoglobulin heavy chain variable (IGHV) region somatic hypermutations (SHMs) in Korean patients with chronic lymphocytic leukemia (CLL). We also analyzed IGH and immunoglobulin kappa (IGK) to identify Korean-specific IGs in CLL. Methods: Next-generation sequencing (NGS)–based gene rearrangements and IGHV SHMs were assessed in 40 patients using IGH leader, IGH FR1, and IGK primers. Flow cytometry, karyotyping, interphase FISH, and NGS-based variant analyses were performed for 165 genes. Results: Clonal IGH and IGK rearrangements were detected in 100.0% and 97.5% of patients, respectively. Clonal size was generally smaller per NGS than per flow cytometry, particularly when using the IGH leader (median: 52.5%) versus the IGH FR1 primer set (73.2%). IGHV SHMs occurred in approximately 70% of patients; 10% showed primer set discrepancies. The incidence of IGHV SHMs was low in patients at high risk (i.e., with TP53 abnormalities; complex karyotypes; and ATM, NOTCH1, SF3B1, or BIRC3 variants). IGHV3 was the most common IGHV (58.3%), and IGHV4-34 was most frequently identified (14.6%). IGHV1 and IGHV1-69 usage differed significantly between Koreans and westerners. IGHJ4 was the most common IGHJ (56.3%). A single IGKV–IGKJ gene rearrangement was most frequently observed (18.9%), whereas intron-KDE was the most common rearrangement (30.6%). Conclusions NGS may underestimate CLL clonal size, particularly when using the IGH leader primer set. IGHV SHMs were inversely associated with negative prognostic factors.Our data suggest ethnic differences in CLL pathogenesis.

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.

Objective: Unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) has emerged as an alternative to open TLIF. However, limited evidence is available regarding the application of 3-dimensional (3D)-printed titanium cages in UBE-TLIF. We aimed to compare the clinical outcomes and fusion rates of UBE-TLIF and open TLIF using 3D-printed titanium cages. Methods: We retrospectively reviewed patients who underwent single-level TLIF with 3D-printed titanium cages between 2021 and 2023. The inclusion criterion was degenerative lumbar stenosis, while the exclusion criteria were trauma, infection, and multilevel surgery. Clinical and radiologic outcomes were compared between the UBE-TLIF and open TLIF groups. Results: Twenty-one patients underwent UBE-TLIF, and 21 underwent open TLIF. The visual analogue scale (VAS) for back (p=0.987) and leg pain (p=0.731) did not significantly differ between the groups at 1-year follow-up. However, VAS back pain at postoperative day 2 was significantly lower in the UBE-TLIF group than in the open TLIF group (p<0.001). Solid fusion was achieved in 21 patients (100%) in the open TLIF group and in 20 (95.2%) in the UBE-TLIF group (p=1.000). In multivariable logistic regression analysis, body mass index was the only factor that exhibited a significant relationship (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.53–0.92; p=0.011) with interbody fusion. In contrast, the surgical method (UBE vs. open TLIF) was not a significant factor (OR, 0.47; 95% CI, 0.10–2.21; p=0.337). Conclusion Using a 3D-printed titanium cage for UBE-TLIF may yield comparable fusion rates to those of open TLIF.

Objectives: This study was performed to quantify the impact of coronavirus disease 2019 (COVID-19) on hospital profitability in Korea by analyzing changes in the medical revenue-to-profit ratio (MRPR) and net income before reserve fund allocation (NIBR) before and after the pandemic onset. Additionally, it examined how financial outcomes varied by hospital ownership, geographic location, and type (secondary or tertiary), providing insights into the financial resilience of various hospital types during public health crises. Methods: We conducted a longitudinal analysis using publicly available financial disclosure data from 243 general hospitals in Korea (2016–2022). We then performed a quadrant analysis to classify hospitals based on changes in MRPR and NIBR, identifying patterns of financial impact. For inferential analysis, we employed linear mixed-effects models incorporating a difference-in-differences framework, enabling estimation of both time-varying and hospital-specific effects. Results: Following the onset of COVID-19, MRPR declined significantly, reaching −10.62% in 2020. NIBR initially dropped but later increased, reaching 21.09 billion Korean won per 100 beds in 2022. Quadrant analysis revealed substantial heterogeneity in financial responses, with national/public hospitals experiencing the most severe MRPR decline, whereas educational foundation and medical corporation hospitals displayed stronger financial recovery. Regression results confirmed significant interactions between outcomes after COVID-19 onset and hospital ownership type, indicating differential financial impacts across hospital categories. Conclusions The findings highlight the uneven financial effects of COVID-19 on Korean hospitals, emphasizing the importance of targeted government financial support. Policy measures should prioritize structural financial reforms to ensure hospital sustainability beyond short-term crisis management.

Purpose: Drainage fluid may serve as a biologically informative indicator of immune and infectious status during postsurgical recovery after trauma. However, microbiome shifts in drainage fluid associated with clinical resilience have not yet been characterized. This study aimed to investigate microbial dynamics in drainage fluid across the intensive care unit (ICU) and ward recovery phases in Korean trauma patients. Methods: A total of 25 drainage and 10 stool samples were collected from 10 trauma patients who underwent abdominal surgery at a regional trauma center. Microbial composition was analyzed using 16S ribosomal RNA amplicon sequencing.Alpha and beta diversity were compared between sample types and recovery stages. Linear mixed-effects models were used to identify recovery-associated taxa while adjusting for clinical variables, and predicted metabolic pathways were assessed using PICRUSt2. Results: Drainage fluid harbored distinct microbial communities independent of the intestinal microbiota. Shared taxa between drainage and stool increased significantly in patients with bowel injury, suggesting microbial translocation.Seven genera and 5 species showed significantly decreased abundance during the ward stage, with Modestobacter and Blastococcus tunisiensis demonstrating the highest discriminative ability between recovery stages (area under the curve = 0.721). Predicted metabolic pathways related to fatty acid degradation, amino acid degradation, and pro-inflammatory processes were more active during the ICU stage. Conclusion These findings provide preliminary evidence that drainage fluid microbiome profiles may reflect recovery dynamics following trauma, supporting its potential utility for microbiome-based monitoring and biomarker discovery in trauma surgery.

This case report describes the use of CAD-based digital tooth arrangement to overcome the limitations of conventional methods in a patient with a maxillary arch wider than the average Korean morphology. In such wide arches, average-based tooth arrangement often restricts the ability to adjust the occlusal plane and cusp positions, thereby limiting functional and esthetic reproduction.In this case, virtual tooth arrangement and occlusal analysis were performed using CAD software, and a putty index was fabricated on a 3D-printed reference model to guide the final arrangement. The fabricated maxillary cast metal complete denture and mandibular distal extension removable partial denture successfully achieved bilateral balanced occlusion, and the patient reported high satisfaction in both functional and esthetic aspects. This case highlights the clinical utility of digital tooth arrangement in atypically wide arches and suggests that CAD-assisted workflows can enhance accuracy and reproducibility in clinical prosthodontics.