Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. Methods: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156) Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. Conclusion The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Purpose: This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB). Methods: CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses. Results: Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not. Conclusion CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Purpose: This study compared the diagnostic performance of two attenuation imaging (ATI) modes—low-frequency (3 MHz) and high-frequency (4 MHz)—for assessing hepatic steatosis, with histopathological hepatic fat fraction (HFF) as the reference standard. Methods: This prospective single-center study enrolled participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) scheduled for liver biopsy or surgery between June 2023 and June 2024. Attenuation coefficient (AC) values were consecutively measured using low- and high-frequency ATI modes, while the skin-to-region of interest distance (SRD) was measured simultaneously. Spearman correlation analysis evaluated the relationships of AC with HFF and SRD, and linear regression identified factors affecting AC. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Results: In total, 119 participants (mean age, 37.2±12.0 years; 87 men) were included, with 73 (61.3%) diagnosed with MASLD. HFF ranged from 0% to 50%. The AC values in the lowfrequency mode were significantly higher than those in the high-frequency mode (0.61 vs. 0.54 dB/cm/MHz, P<0.001). HFF significantly influenced AC in both modes, whereas SRD affected AC only in the high-frequency mode (P<0.001). AC correlated positively with HFF in both modes (r_s≥0.514, P<0.001) and negatively with SRD in the high-frequency mode (r_s=-0.338, P<0.001). The AUROC for hepatic steatosis did not differ significantly between the two modes (0.751 vs. 0.771; P=0.609). Conclusion The low-frequency mode produced higher AC values than the high-frequency mode and demonstrated comparable diagnostic accuracy for assessing hepatic steatosis. Unlike the high-frequency mode, the low-frequency mode was not influenced by SRD.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Objectives: . Congenital aural atresia (CAA) is a complex condition that manifests in various forms, including Schuknecht type B stenosis, which is characterized by a congenitally narrow bony external auditory canal (EAC). This study aims to evaluate the long-term surgical outcomes of canal-tympanoplasty in patients with Schuknecht type B CAA. Methods: . The study included 21 ears diagnosed with Schuknecht type B CAA, all of which underwent canal-tympanoplasty. Reconstruction of the large EAC and tympanic membrane involved conchal flap meatoplasty, bony EAC drilling, ossicular reconstruction, and overlay tympanoplasty. Standard pure-tone audiometry was analyzed at multiple post-surgery time points: 3, 6, 12, and 24–60 months. Additionally, the incidence of postoperative complications was assessed. Results: . The hearing outcomes of canal-tympanoplasty in this case series were satisfactory. Serviceable hearing was achieved in all patients after 3 months and was maintained in 85% of patients for 1 year. The air-bone gap improved from a preoperative average of 39.3±15.1 dB to 13.7±7.4 dB at 3 months, 16.4±10.5 dB at 6 months, 19.1±11.7 dB at 12 months, and 21.5±16.1 dB at 2–5 years postoperatively. Three patients required revision canal-tympanoplasty due to hearing deterioration, representing 14.3% of the cases. There were no instances of postoperative infection, facial nerve weakness, vertigo, deterioration of bone conduction thresholds, or complete restenosis of the EAC. Conclusion . Canal-tympanoplasty proved to be a satisfactory surgical intervention for patients with Schuknecht type B CAA. This procedure led to significant improvements in hearing outcomes, providing serviceable hearing that lasted for several years. Moreover, the risk of postoperative hearing deterioration and/or the need for revision surgery within 1 year was considered acceptable.

Background: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated. Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood. Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively). Conclusion These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.