Background: The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT. Methods: We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression. Results: Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03). Conclusions In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.

Enterococcus faecium, particularly in its multidrug-resistant forms, causes invasive nosocomial infections. Given the limited data comparing the effectiveness of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the CLSI clinical breakpoints (CBPs) for quinupristin–dalfopristin (QD) resistance and the need to evaluate their practical application, we retrospectively investigated the susceptibility patterns of 287 E.faecium bloodstream isolates from Korean hospitals to QD using the updated EUCAST and CLSI CBPs and two antimicrobial susceptibility testing methods: disk diffusion (DD) and Sensititre broth microdilution (Sensititre). QD resistance rates were 5.9% (CLSI) and 18.8% (EUCAST) for DD and 22.6% (CLSI) and 28.2% (EUCAST) for Sensititre. The most prevalent QD resistance gene types among QD-resistant isolates were ermB+msrC+ or ermB– msrC+. Categorical agreement between DD and Sensititre ranged from 77.7% to 90.7%, depending on the testing method and CBPs applied. The EUCAST zone diameter CBPs more effectively help identify QD-resistant E. faecium isolates using the DD method than the CLSI zone diameter CBPs. In comparison, the CLSI minimum inhibitory concentration (MIC) CBPs provide more reliable results for resistance classification in the Sensititre method than EUCAST MIC CBPs. These findings would help improve clinical decision-making for treating multidrug-resistant E. faecium infections.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

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.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

Purpose: This study investigated the impact of nusinersen on health-related quality of life (HRQoL), functional performance, and caregiver burden in patients with infantile-onset spinal muscular atrophy (SMA), addressing a growing interest in disease-modifying treatments. Methods: A 14-month observational study was conducted to evaluate changes in HRQoL and functional performance using the Pediatric Quality of Life Inventory (PedsQL) Infant Scales and the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). Caregiver burden was assessed through the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Motor function was evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Correlations between CHOP INTEND scores, functional performance, and caregiver burden were analyzed. Results: Eight patients with infantile-onset SMA and their caregivers participated, with a median treatment initiation age of 4.6 months (range, 1.1 to 15.1). CHOP INTEND scores showed significant improvement (P<0.001), whereas all PedsQL Infant Scale scores declined. Conversely, the PEDI-CAT revealed significant enhancements in daily activities, mobility, and social-cognitive domains (all P<0.001). Caregiver burden lessened across most dimensions (P<0.001), with the exception of the time-related burden (P=0.731). Higher CHOP INTEND scores correlated with improvements in PEDI-CAT domains and a reduction in caregiver burden related to sitting/play and transfer activities. Conclusion The study demonstrates the positive effects of nusinersen on functional performance and caregiver burden in patients with infantile-onset SMA. However, discrepancies were observed in HRQoL outcomes, suggesting a need for further research that includes SMA-specific outcome measures to comprehensively assess the treatment's impact on patients' lives.