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.

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease driven by autoantibodies against BP180 and BP230. While type 2 inflammation plays a key role, the precise immune cell alterations and transcriptomic changes remain unclear. Objective: To characterize immune cell composition and transcriptomic changes in BP patients using fluorescence-activated cell sorting (FACS)-based immunophenotyping and RNA sequencing. Methods: A case-control study was conducted on 10 newly diagnosed, treatment-naive BP patients and six healthy controls. Disease activity was assessed using the Bullous Pemphigoid Disease Area Index (BPDAI). Peripheral blood mononuclear cells were isolated for FACS analysis to determine immune cell subsets. RNA sequencing was performed to identify differentially expressed genes (DEGs) and enriched pathways. Statistical analyses included t-tests, Mann-Whitney U tests, and correlation analysis. Results: FACS analysis revealed a reduction in CD4 + T cells, T helper 2 (Th2), and B cells in BP patients (p<0.05), alongside an increase in M2a-like monocytes (p<0.001). RNA sequencing identified 262 DEGs, with secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237 being the most significantly upregulated. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) and SAM domain, SH3 domain, and nuclear localization signals 1 (SAMSN1) positively correlated with BPDAI (p<0.001). Gene ontology analysis highlighted enrichment in inflammatory responses and neutrophil degranulation pathways. Conclusion BP patients show distinct immune dysregulation, including decreased CD4 + T cells, Th2, and B cells, increased M2a-like monocytes, altered gene expression profiles, and correlations between PSTPIP2, SAMSN1 and disease activity. These findings provide insights into pathogenesis and potential therapeutic targets of BP.

Background: Circulating tumor DNA (ctDNA) profiling from peripheral blood allows relatively noninvasive monitoring of solid tumors; however, its utility post-surgery or chemotherapy in colorectal cancer remains underexplored. We evaluated the clinical implications of a ctDNA next-generation sequencing (NGS) panel post-surgery or chemotherapy in patients with colorectal cancer. Methods: We collected samples from 23 patients with colorectal cancer (17 men, median age 65 yrs) at baseline and post-surgery or chemotherapy at the National Cancer Center, Korea, between January 2021 and September 2023. ctDNA was analyzed using an NGS panel including 46 genes, and variant allele frequencies (VAFs) were determined. Followup samples were analyzed using the NGS panel or droplet digital PCR (ddPCR) when probes were available. Clinical status was compared with ctDNA results, and survival was analyzed using a time-dependent Cox model. Results: Mutations were identified in 13 out of 14 patients (92.8%) with stage II/III cancer and in all nine patients (100%) with stage IV cancer. Mutations were detected in KRAS (N = 15, 65%), APC (N = 8, 35%), TP53 (N = 7, 30%), PIK3CA (N = 5, 22%), and RET (N = 4, 17%). A 1% increase in KRAS and TP53 VAFs was associated with 48% and 32% increased mortality risk, respectively. Changes in VAF correlated well with clinical findings. Conclusions The detection of and an increase in KRAS and TP53 VAFs were associated with poor prognosis. ddPCR-based ctDNA monitoring results were comparable to those obtained with the NGS panel. ctDNA monitoring during treatment is clinically informative in managing colorectal cancer.

Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing. Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89). Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM. Conclusions Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.

Background: Group B Streptococcus (GBS) is one of the leading causes of neonatal earlyonset sepsis, resulting in high mortality and significant comorbidity. Intrapartum penicillin prophylaxis is recommended for pregnant women with GBS colonization to prevent vertical transmission. For pregnant women at high risk of anaphylaxis to penicillin, clindamycin is recommended only if the susceptibility of GBS isolates has been identified. We retrospectively examined the GBS detection rate and clindamycin resistance among Korean women of reproductive age over the last 20 years. Methods: Microbiologic studies using vaginal, vaginal–rectal or vaginal–perianal swabs from female patients 15–49 years of age during 2003–2022 were reviewed. Annual GBS detection rates and clindamycin resistance rates were calculated. The study period was divided into two periods (period 1, 2003–2015; period 2, 2016–2022) based on the introduction of universal culture-based GBS screening in our center in 2016. GBS detection rates and clindamycin resistance rates were compared between the periods using χ2 tests. Results: A total of 14,571 women were tested 16,879 times and GBS was isolated in 1,054 tests (6.2%), with 423 clindamycin-resistant isolates (40.1%). The GBS detection rate increased from 3.4% (301/8,869) in period 1 to 9.4% (2,753/8,010) in period 2 (P < 0.001). Even during period 1, the GBS detection rate was higher in 2009–2015 compared to 2003–2008 (P < 0.001). Clindamycin resistance rates have remained at similar levels since 2009, which were 39.5% (199/301) in period 1 and 40.2% (303/753) in period 2 (P = 0.833). Conclusion This study demonstrated that GBS detection rates in Korean women of reproductive age significantly increased almost three times during the twenty years of the study period, with a persistently high clindamycin resistance rate of up to 40%.

Background: To assess the quality of life (QoL) and treatment satisfaction with intermittently-scanned continuous glucose monitoring (isCGM) in women with gestational diabetes mellitus (GDM). Methods: This prospective observational study included 189 women with GDM who completed the Korean version of the Audit of Diabetes-Dependent Quality of Life Questionnaire (K-ADDQoL). Among them, 25 women who utilized isCGM between gestational weeks 30 and 34 completed the Korean version of the Diabetes Treatment Satisfaction Questionnaire change version (K-DTSQc) to evaluate their satisfaction with isCGM during pregnancy. Results: GDM had a negative impact on the perceived QoL in 89.4% of the women. All 19 domains of the K-ADDQoL were adversely influenced by GDM, with the most significant impact on the freedom to eat (weighted impact score, −6.98 ± 2.49, P < 0.001) and the least impact on the sex life (−0.25 ± 0.80, P = 0.008). Younger women and those treated with insulin perceived themselves as being more affected in their QoL due to GDM. Women perceived to have less effect on their QoL attributed to GDM exhibited higher ΔHbA1c one year after delivery (ΔHbA1c, 0.3 ± 0.4% vs. 0.0 ± 0.4% in less affected vs. more affected women). The utilization of isCGM improved treatment satisfaction (overall satisfaction score, 10.36 ± 9.21, P < 0.001), independent of glycemic control during pregnancy. Conclusion Although GDM negatively affects the perceived QoL during pregnancy, attentiveness to GDM management may have a positive impact on long-term glycemic control.Moreover, employing isCGM can enhance treatment satisfaction in women with GDM.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Background: In 2023, we experienced an outbreak from a case of undiagnosed crusted scabies, resulting in a significant number of exposed individuals and secondary cases. In this report, we describe the outbreak control measures, the attack rate, and the risk factors for acquisition of scabies among healthcare workers (HCWs). Methods: This study was conducted in a 2,700-bed tertiary care hospital in Seoul, South Korea. The attack rate was defined both for microscopic proven cases per exposed individuals and as the sum of proven and probable cases per exposed individuals. Outbreak control measures included identifying and treating all potentially exposed individuals with or without symptoms, as well as environmental disinfection. Results: From the index, there was potential quinary transmission resulting in 63 proven cases, 142 probable cases, and a total of 1,820 exposed individuals, including 734 contacts from the index case. The attack rate from the index was 7% (50/734) based on proven cases and 19% (138/734) based on proven and probable cases. Among the 526 HCWs who received preemptive topical treatment with permethrin applied once, 21 (4%) were later diagnosed as scabies. In addition, 5 of 20 HCWs (25%) with initial proven scabies had a persistent positive microscopic exam after four permethrin treatments. In the case group, there were significantly more nurses (60% vs. 43%, P = 0.007) and nurse assistants (20% vs. 9%, P = 0.006). There were significantly more cases than controls involving direct contact with the index case (94% vs. 64%, P < 0.001). Conclusion Lowering the threshold for suspicion of crusted scabies is important, as a single missed case could lead to a large outbreak. Simultaneously applying preemptive permethrin cream to all potentially exposed individuals might have been effective in preventing further transmission. However, caution is needed because the development of scabies or persistent scabies is possible even with preemptive or therapeutic treatment.

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: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.