Background: and Purpose The relationship between thrombus histology and long-term stroke patient outcomes remains unexplored. We aimed to determine whether the histological characteristics of thrombi are associated with long-term outcomes in stroke patients and to identify the thrombus features linked to these outcomes. Methods: This retrospective multicenter cohort study included 512 patients with ischemic stroke who underwent endovascular thrombectomy between July 2017 and July 2023. Patients were followed up for long-term major adverse cardiovascular events occurrence. Thrombus histology was assessed using immunohistochemistry, including the proportion of fibrin, red blood cells, and platelets, as well as the distribution patterns categorized as layered, erythrocytic, diffuse platelet, and mixed. Results: During a median follow-up of 38.1 months, 164 patients experienced major adverse cardiovascular events, with an incidence rate of 3.02 per 100 person-years. Major adverse cardiovascular events occurrence was associated with the diffuse platelet pattern and proportion of platelets and red blood cells within the thrombus. After adjusting for confounders, the diffuse platelet pattern independently predicted major adverse cardiovascular events, including mortality and stroke recurrence. Subgroup analysis also demonstrated that the association between the diffuse platelet pattern and major adverse cardiovascular events was consistent across key clinical subgroups based on age (≥65 vs. <65 yr), atrial fibrillation, cancer status, and discharge medications. Conclusions Thrombus histology could provide predictive value for long-term prognosis. In particular, histological distribution patterns may be more important than simple composition in thrombus research, including in the prediction of prognosis.

Background: Dual energy X-ray absorptiometry (DXA) measurements vary among instruments from different manufacturers. This study aimed to assess the correlation between bone mineral density (BMD) and body composition measured by the GE Lunar Prodigy and Hologic Horizon W DXA systems and to develop conversion equations. Methods: A total of 120 healthy volunteers (59 males, 61 females) aged 20 to 70 years were scanned on both DXA systems on the same day. BMD was measured at the lumbar spine (L1-L4) and bilateral femurs. Body composition parameters were measured for the whole body and regional sites. Bland-Altman analysis, Pearson correlation, and concordance correlation coefficient (CCC) were used to assess agreement. Linear regression was performed to derive conversion equations. Results: The Hologic system measured BMD values 14% to 20% lower at the lumbar spine and 8% to 17% lower at femoral sites compared to the GE Lunar system (all P<0.0001). Lean mass values were 4% to 10% lower on the Hologic system. Very strong correlations were observed for both BMD (r=0.944-0.980) and lean mass (r=0.963-0.984). Cross-calibration equations were developed for all measurement sites. Conclusions Despite significant systematic differences, there was very high correlation between the two DXA systems. The conversion equations can facilitate comparison of measurements between these systems in clinical practice and research.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

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: Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD. Methods: This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC. Results: Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline. Conclusion We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.

Background: Factors influencing the decline in forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC) for chronic obstructive pulmonary disease (COPD) progression remain uncertain. We aimed to identify risk factors associated with rapid FEV1 / FVC decline in patients with COPD. Methods: This multi-center observational study was conducted from January 2012 to December 2022. Eligible patients were monitored with symptoms, spirometric tests, and treatment patterns over 3 years. Rapid FEV1 /FVC decliners were defined as the quartile of patients exhibiting the highest annualized percentage decline in FEV1 /FVC. Results: Among 1,725 patients, 435 exhibited rapid FEV1 /FVC decline, with an annual change of −2.5%p (interquartile range, −3.5 to −2.0). Rapid FEV1 /FVC decliners exhibited lower body mass index (BMI), higher smoking rates, elevated post-bronchodilator (BD) FEV1 , higher post-BD FEV1 / FVC, and a lower prevalence of Staging of Airflow Obstruction by Ratio (STAR) stage IV. Rapid FEV1 /FVC decline was not linked to the annual exacerbation rate, but there was an association with symptom deterioration and FEV1 decline. In multivariable analyses, low BMI, current smoking, increased modified Medical Research Council dyspnoea score, low post-BD FEV1 , low STAR stage, high forced mid-expiratory flow (FEF 25-75% ), accelerated FEV1 decline, and not initiating dual BD therapy were identified as independent risk factors for rapid FEV1 /FVC decline. Conclusion We identified the risk factors for rapid FEV1 /FVC decline, including BMI, smoking, symptoms deterioration, FEV1 decline, and adherence to standard inhaler treatment. Our findings underscore the potential benefits of maintaining consistent use of long-acting beta-agonist/long-acting muscarinic antagonist even in the presence of worsening symptoms, in attenuating FEV1 /FVC decline.

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: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.