Background: Autosomal dominant giant platelet syndrome (GPS) is characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies in leukocytes.Previous studies suggest relatively preserved platelet structure and function, implicating impaired megakaryocyte fragmentation. This study aimed to identify myosin heavy chain 9 (MYH9) mutations in Korean patients with GPS and to define the associated clinical, molecular and functional characteristics. Methods: After detailed personal and family history taking, peripheral blood smears were reviewed for platelet size, count, and leukocyte inclusions. MYH9 mutations were analyzed in peripheral blood mononuclear cells by direct sequencing of selected exons or complementary DNA (cDNA). Computer-assisted structural modeling was performed to evaluate the functional consequences of identified mutations. Results: Twenty-two affected individuals from six unrelated families were diagnosed with hereditary macrothrombocytopenia consistent with GPS. The median platelet count was 59,000/L, and the mean platelet volume was markedly increased (17.8 fL). Platelets ranged from approximately half to 1.5 times the size of red blood cells.Döhle-like inclusions were observed in 25-33% of leukocytes in four families. Extrahematologic manifestations included hearing impairment (family with Ile1816Val) and renal involvement, ranging from mild proteinuria to chronic renal failure requiring renal transplantation (family with Lys373Asn). Five families harbored MYH9 mutations—Arg1933Ter, Trp33Cys (novel), Lys373Asn, Ile1816Val, and Arg1165Cys—located in exons 40, 1, 10, 37, and 26, respectively; mutations segregated with affected status.Biochemical analysis revealed decreased MYH9 in soluble fractions with increased insoluble pellets; Trp33Cys and Lys373Asn produced aberrant approximately 140 kDa bands in addition to the normal 224 kDa band. Modeling localized Trp33Cys to the proximal myosin head region implicated in actin interaction. Conclusion Five GPS-associated MYH9 mutations were identified, including a novel Trp33Cys variant. Altered MYH9 solubility and disturbed protein–protein interactions may contribute to disease pathogenesis.

Background: The Dejour classification is widely accepted for grading the severity of trochlear dysplasia. However, whether it serves as a reliable prognostic marker for patellar instability surgery or a guide for clinical decision-making has yet to be established. Medial patellofemoral ligament (MPFL) reconstruction, with or without tibial tubercle osteotomy (TTO), yields comparable outcomes across Dejour grades. Nonetheless, we hypothesized that specific trochlear parameters would be more significant predictors of surgical results. Methods: This study included patients who underwent MPFL reconstruction, with or without TTO, for recurrent patellar dislocation at a single institution between 2010 and 2023. Patients with at least 1 year of follow-up were included. Preoperative demographics, radiographic measurements such as sulcus angle, lateral trochlear inclination (LTI), and trochlear depth, patient-reported outcome measures (PROMs), and intraoperative findings including cartilage status were analyzed. Severe trochlear dysplasia (STD) was categorized as Dejour B/D, while non-STD encompassed all other cases, and these 2 groups were compared. Postoperative PROMs were assessed at 1 year postoperatively and at the final follow-up. A noninferiority test was performed using Kujala, Lysholm, and International Knee Documentation Committee (IKDC) scores, with the inferiority margin defined by the minimal clinically important difference (MCID). Linear relationships between LTI, a widely used indicator of trochleoplasty, and PROMs were evaluated. Additionally, differences in the proportion of patients achieving MCID, substantial clinical benefit, and patient-acceptable symptom state were analyzed using odds ratios. Results: Forty-two knees (41 patients) were finally enrolled. Radiographic measurements, except for LTI at the most proximal trochlea, showed no significant differences between the STD and non-STD groups. Clinical outcomes also demonstrated no significant differences between the 2 groups, and noninferiority was confirmed. When analyzed based on LTI, no differences in PROMs were observed at the postoperative 1 year. However, at the final follow-up (mean, 37.27 months), the most proximal trochlear LTI showed significant correlations with both Kujala and Knee Injury and Osteoarthritis Outcome Score over the follow-up period. Conclusions MPFL reconstruction, with or without TTO, leads to similar clinical improvements for STD classified by Dejour criteria. However, when assessed using proximal LTI, dysplasia’s role as a prognostic factor should be considered.

Background: When positioning the acetabular component for total hip arthroplasty (THA) in patients with sequelae of LeggCalvé-Perthes disease (LCPD), elevating the center of rotation (COR) of the hip is often unavoidable. We aimed to compare the outcomes between the preserved and elevated COR groups in patients with sequelae of LCPD. Methods: We enrolled 53 patients who underwent primary THA for sequelae of LCPD between 2006 and 2019. Patients were divided into 2 groups based on the postoperative COR position: 19 in the preserved COR group and 34 in the elevated COR group.The mean elevation of COR was 2.7 mm (range, 0–5.0 mm) in the preserved COR group and 8.1 mm (range, 6.0–12.0 mm) in the elevated COR group. Radiological outcomes, such as osteolysis and implant loosening, were evaluated. Additionally, reoperation, perioperative complications, limping gait, pelvic obliquity, and the modified Harris hip score (mHHS) were assessed. Results: There were no significant differences in radiological or clinical outcomes between the 2 groups. Neither osteolysis nor implant loosening was observed, and no reoperations were required. Intraoperative periprosthetic femoral fractures occurred in 3 cases (6%), but no cases of sciatic nerve palsy were observed. Residual limping gait was noted in 10 patients (19%), and pelvic obliquity persisted in 8 patients (15%). At the last follow-up, the mean mHHS was 89.2. Conclusions The 5–17-year follow-up results of primary cementless THA in patients with sequelae of LCPD were satisfactory.Furthermore, a moderate elevation of the COR, with a mean of 8.1 mm (range, 6.0–12.0 mm), did not significantly affect the outcomes of THA in these patients. Therefore, a moderate elevation of the COR can be considered an acceptable option for patients undergoing THA with sequelae of LCPD.

Background: and Purpose: Given the irreversible nature of dementia, this study examined the effects of a 20-week exercise-based dementia prevention program in community-dwelling older adults, focusing on prior exercise experience and program adherence. Methods: In this exploratory, non-randomized trial, 55 older adults (65–79 years) were allocated to an intervention (n=26) or control (n=29) group, and blinding was not feasible.The intervention comprised supervised rhythmic aerobic exercise with cognitive-motor components performed three times per week. Cognition was the primary outcome, and secondary outcomes included physical fitness, blood pressure, and blood biomarkers.Subgroup analyses classified participants by prior exercise experience and intervention exposure: G1 and G2 comprised control subgroups with no intervention exposure, whereas G3 and G4 comprised intervention-exposed subgroups stratified by adherence. Results: No significant group-by-time interactions were observed for cognitive outcomes.Participants with prior exercise experience and low adherence (G2) showed significant improvement on the Korean Mini-Mental State Examination (β=1.66, p=0.024) despite declines in physical fitness, whereas higher adherence in G3–G4 was associated with stable or favorable physical performance, with G4 showing a positive trend in the 30-second sit-tostand test. Systolic blood pressure decreased significantly in G2–G4. Conclusions Although overall cognitive gains were modest and not group specific, prior exercise experience and sustained adherence were associated with favorable changes in physical fitness and vascular outcomes, suggesting that tailored multicomponent exercise programs and long-term engagement may help promote cognitive health in older adults.

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.

Background: and Purpose: Tailored physical exercise interventions have the potential to promote cognitive health in older adults and offer significant advantages for those more vulnerable to decline. The specific relationship between physical fitness and cognition among the elderly has not been clearly established. The purpose of this investigation was to assess the relationship between physical fitness and cognitive function in older Korean adults. Methods: Eighty-four community-dwelling older adults (mean age: 70.7±5.3 years; 81.0% female) completed a standardized physical fitness battery assessing handgrip strength, sit-and-reach, 30-second sit-to-stand, 2-minute stationary march, 3-m sit-walk-and-return, figure-8-walk, and T-wall response time. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Descriptive statistics, partial correlation analyses, and stepwise multiple linear regression were conducted. Results: Slower T-wall response time was significantly correlated with lower RBANS total index, immediate memory, and delayed memory scores. In regression models, slower T-wall response time was independently associated with lower RBANS total index (β=−0.234, p=0.026) and delayed memory scores (β=−0.295, p=0.029). The regression model for immediate memory was not statistically significant overall; therefore, no predictive conclusion was drawn for this domain. Higher education showed a significant positive association with cognitive performance. Conclusions Coordination, as measured by T-wall response time, emerged as the only physical fitness component consistently associated with cognitive performance in older adults. Coordination-related fitness may be an important correlate of cognitive function in older adults and a promising target for future exercise interventions.

Background/Aims: Early detection and removal of colon polyps are critical for preventing colorectal cancer. Computer-aided detection (CADe) systems have been introduced to increase the polyp detection rate (PDR) during colonoscopy, potentially enhancing its effectiveness. This study aimed to evaluate the efficacy of a CADe system in colorectal neoplasm detection. Methods: This prospective, randomized controlled trial was conducted at two tertiary centers (May 2023 to April 2025). Patients were randomly assigned to CADe or conventional colonoscopy and underwent screening, surveillance, or diagnostic colonoscopy. The primary endpoint was the adenoma detection rate (ADR), while the secondary endpoints were the PDR, relative risk (RR) of polyp detection, adenomas per colonoscopy (APC), and factors influencing adenoma detection. Results: Of 1,004 enrolled patients, 998 were randomly allocated into CADe and conventional colonoscopy groups (497 CADe system and 501 conventional colonoscopy). The CADe group had greater polyp counts (2.2 per colonoscopy vs 1.4 per colonoscopy; p<0.001) and APC values (1.2 vs 0.8; p<0.001). The CADe group showed significantly higher PDRs (72.2% vs 54.5%;p<0.001; RR, 2.173; 95% confidence interval [CI], 1.669 to 2.828) and ADRs (52.3% vs 36.1%;p<0.001; RR, 1.940; 95% CI, 1.505 to 2.499). CADe also significantly increased the detection rate of hyperplastic polyps (p=0.007; RR, 1.474; 95% CI, 1.113 to 1.952) and increased the detection rates across all sizes and locations. In multivariable analysis, CADe use was the strongest independent predictor of adenoma detection (odds ratio, 1.914; 95% CI, 1.467 to 2.496), outweighing male sex, older age, diagnostic indication, and withdrawal time. Conclusions Real-time CADe-assisted colonoscopy significantly increased PDR and ADR and proved to be a strong independent predictor of adenoma detection (cris.nih.go.kr, KCT0009664).

Background/Aims: Recent advances in computer-aided diagnosis (CADx) systems have demonstrated expert-level accuracy in the optical diagnosis of colorectal polyps. High-confidence (HC) diagnoses have been defined as those made within 3 seconds without hesitation, and these systems have been shown to improve diagnostic accuracy. We aimed to evaluate the performance of endoscopists with varying levels of experience in diagnosing colorectal polyps with the assistance of a new CADx system applying the 3-second rule and without artificial intelligence assistance. Methods: In this multicenter ex vivo study, 35 endoscopists assessed 100 polyps (51 adenomas, 39 hyperplastic polyps, 10 sessile serrated lesions) using narrow-band imaging video clips on an online platform. Assessments consisted of individual endoscopist diagnosis and CADx-assisted diagnosis. HC assignments followed the 3-second rule in both phases. Performance metrics included HC accuracy, HC rate, and adherence to the Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds. Results: HC diagnostic accuracy improved from 78.3% (95% confidence interval [CI], 76.6% to 80.0%) to 89.8% (95% CI, 88.6% to 90.9%) with CADx assistance (p<0.001). The proportion of HC predictions increased from 64.2% to 75.4% (p<0.001). Novice endoscopists showed marked improvement with CADx (74.1% vs 88.8%; p<0.001). CADx-assisted diagnoses nearly met SODA and PIVI thresholds under the 3-second rule. Additional analysis demonstrated that CADx assistance significantly improved interobserver agreement and ground truth, particularly for novices (κ=0.37 to κ=0.65; p<0.001). Conclusions Integrating CADx with the 3-second rule significantly enhances the performance of endoscopists in the optical diagnosis of colorectal polyps, with the greatest benefit observed among novice endoscopists.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.