Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background: This study aimed to report the short- and midterm outcomes of arthroscopic rotator cuff repair (ARCR) and reverse shoulder arthroplasty (RSA) in weight-bearing shoulders. Methods: This retrospective multicenter study included 19 cases of ARCR and 10 cases of RSA performed in weight-bearing shoulders from 2009 to 2021. In the ARCR group, postoperative 6-month magnetic resonance imaging confirmed the tendon integrity. In the RSA group, scapular notching, acromial fracture, and implant failure were assessed using plain radiographs, and complications were recorded. In both groups, preoperative and postoperative range of motion and functional scores were documented, along with subjective satisfaction and arm use for weight-bearing on the shoulders. For patients followed up for > 5 years, a midterm analysis was performed. Results: The ARCR group included 8 men and 11 women (average age, 58.8 ± 8.0 years). Initially, Patte types 1, 2, and 3 were noted in 9, 8, and 2 patients, respectively, and 4 patients exhibited full-thickness subscapularis tears. Four patients showed supraspinatus retear, and 2 patients showed subscapularis retear. Retear of any rotator cuff was observed in 5 patients (26.3%). Twelve patients were followed up for > 5 years; 11 (91.7%) used their operated arm for weight-bearing and 9 (75.0%) were satisfied. The RSA group included 5 men and 5 women (average age, 74.3 ± 7.9 years). Procedures included RSAs for cuff tear arthropathy (n = 6), osteoarthritis (n = 3), and fracture nonunion (n = 1). No cases of dislocation, prosthesis loosening, or disassociation were observed throughout the follow-up. However, 1 patient required implant removal due to infection, and 4 patients showed stage 1 scapular notching. Five patients were followed up for > 5 years, all of whom expressed satisfaction and used their operated arms for weight-bearing, despite mean forward flexion (107.5° ± 12.6°) and American Shoulder and Elbow Surgeons score (61.5 ± 5.3) being less than reported patient acceptable symptomatic state (110° and 76, respectively). Conclusions Both ARCR and RSA showed promising outcomes in terms of weight-bearing on the operated arm and subjective satisfaction at short- and midterm follow-up. Therefore, neither of these surgeries should be considered contraindicated for patients with weight-bearing shoulder conditions.

Background: This study aimed to report the short- and midterm outcomes of arthroscopic rotator cuff repair (ARCR) and reverse shoulder arthroplasty (RSA) in weight-bearing shoulders. Methods: This retrospective multicenter study included 19 cases of ARCR and 10 cases of RSA performed in weight-bearing shoulders from 2009 to 2021. In the ARCR group, postoperative 6-month magnetic resonance imaging confirmed the tendon integrity. In the RSA group, scapular notching, acromial fracture, and implant failure were assessed using plain radiographs, and complications were recorded. In both groups, preoperative and postoperative range of motion and functional scores were documented, along with subjective satisfaction and arm use for weight-bearing on the shoulders. For patients followed up for > 5 years, a midterm analysis was performed. Results: The ARCR group included 8 men and 11 women (average age, 58.8 ± 8.0 years). Initially, Patte types 1, 2, and 3 were noted in 9, 8, and 2 patients, respectively, and 4 patients exhibited full-thickness subscapularis tears. Four patients showed supraspinatus retear, and 2 patients showed subscapularis retear. Retear of any rotator cuff was observed in 5 patients (26.3%). Twelve patients were followed up for > 5 years; 11 (91.7%) used their operated arm for weight-bearing and 9 (75.0%) were satisfied. The RSA group included 5 men and 5 women (average age, 74.3 ± 7.9 years). Procedures included RSAs for cuff tear arthropathy (n = 6), osteoarthritis (n = 3), and fracture nonunion (n = 1). No cases of dislocation, prosthesis loosening, or disassociation were observed throughout the follow-up. However, 1 patient required implant removal due to infection, and 4 patients showed stage 1 scapular notching. Five patients were followed up for > 5 years, all of whom expressed satisfaction and used their operated arms for weight-bearing, despite mean forward flexion (107.5° ± 12.6°) and American Shoulder and Elbow Surgeons score (61.5 ± 5.3) being less than reported patient acceptable symptomatic state (110° and 76, respectively). Conclusions Both ARCR and RSA showed promising outcomes in terms of weight-bearing on the operated arm and subjective satisfaction at short- and midterm follow-up. Therefore, neither of these surgeries should be considered contraindicated for patients with weight-bearing shoulder conditions.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment. Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed. Results: Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953). Conclusion Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.

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: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.