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.

Background/Aims: Gastroesophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM) is a significant challenge. Disruption of the lower esophageal sphincter during POEM and dysfunction of the crural diaphragm, which contributes to esophagogastric junction pressure, may lead to GERD after POEM. We aim to identify predictors of GERD after POEM and focus on physiological parameters of esophagogastric junction pressure in patients with achalasia before POEM. Methods: We retrospectively analyzed a prospectively collected database of patients who underwent POEM between July 2016 and August 2023. Ninety-two patients with achalasia who underwent high-resolution manometry and endoscopy before and after POEM were included. Results: Forty-nine (53.3%) patients were diagnosed with GERD. Patient demographics, achalasia subtypes, prior treatments, myotomy length, and myotomy orientation were not associated with GERD after POEM. Loss of inspiratory augmentation before POEM was associated with GERD after POEM (P < 0.05). GERD occurred more frequently in patients with a shorter intra-abdominal lower esophageal sphincter length before POEM. Type III esophagogastric junction morphology in the GERD group (37.1%) was more common than that in the non-GERD group (15.8%). Loss of inspiratory augmentation occurred more frequently in patients with type III esophagogastric junction pressure morphology. Conclusion Loss of inspiratory augmentation may predict GERD after POEM.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

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.

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.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Genetic neuromuscular diseases (NMDs) are a heterogeneous group of conditions that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study was performed to identify pathogenic or likely pathogenic variants (PLPVs), calculate carrier frequencies, and predict the genetic prevalence of autosomal recessive-NMDs (AR-NMDs) in a Korean population. Methods: In total, 267 genes were associated with AR-NMDs. We analyzed genetic variants from 984 Korean whole genomes and identified PLPVs to assess the carrier frequency and genetic prevalence of the variants. Results: We identified 165 PLPVs, including 75 literature verified and 90 manually verified variants. Most PLPVs in AR-NMD genes were frameshifts (61, 37.0%), followed by nonsense (36, 21.8%), missense (35, 21.2%), and splice variants (28, 17.0%). The carrier frequency of the AR-NMDs was 27.1%. DYSF exhibited the highest carrier frequency (1.63%), followed by GAA (1.55%), HEXB (1.53%), PREPL (0.76%), NEB (0.66%), ADSS1 (0.65%), ALPK3 (0.65%), and CHRNG (0.65%). The predicted genetic prevalence of AR-NMDs in the Korean population was 38.0 cases per 100,000 individuals. DYSF (6.7 cases per 100,000 individuals) showed the highest genetic prevalence. The variant with the highest allele frequency was c.1250C>T in HEXB at 0.00764, followed by c.[752T>C; c.761C>T] in GAA at 0.00505, and c.2055+2T>G in DYSF at 0.00437. Conclusion Our study suggests that 27.1% of the Korean population are healthy carriers of at least one AR-NMD causing PLPV, revealing the genetic prevalence of NMDs in the Korean population.

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.

Background and Objectives: Hearing loss significantly affects communication, psychosocial well-being, and quality of life. This study analyzes the National Health Insurance Service database to assess the trends and characteristics of hearing loss in South Korea from 2010 to 2020.Subjects and Method The database encompasses 97% of the Korean population, providing comprehensive data on medical history, prescriptions, and health examinations. The analysis used the World Health Organization’s ICD-10 definitions to categorize hearing loss types and examine their prevalence and incidence across various demographics over 11 years. Results: There was an overall annual increase of 4.62% in diagnosed cases of hearing loss, with the most significant rise among the elderly. The rate of increase accelerated from 3.32% between 2010 and 2014 to 6.49% between 2014 and 2020, corresponding with the improved hearing aid access facilitated by policy changes. Women showed a slightly higher increase than men. The data also indicated a consistent rise in abnormal hearing test results during health examinations, especially in older adults. Conclusion The study highlights an increasing trend in hearing loss diagnoses, driven by an aging population and enhanced detection facilitated by policy changes. These findings emphasize the need for continuous monitoring and targeted health policies to manage hearing loss effectively, offering valuable insights for global health management and policy development.