Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Serum calcium and magnesium levels are a key factor of the coagulation cascade and may potentially contribute to the pathophysiology of intracerebral hemorrhage (ICH) expansion. The aim of this study was to attain and sustain target levels of serum calcium and magnesium for three days following admission. Methods: A single-blind, prospective, multicenter randomized study was conducted from 2019 to 2022 years, enrolling acute ICH patients aged 18–80 years, with radiological diagnosis and without surgical intervention. Participants were randomly assigned in a 1:1 ratio to either the study group or the control group. In the study group, the target serum levels of calcium (9–10.2 mg/dL) and magnesium (2–3 mg/dL) were actively achieved and maintained for a duration of 3 days following admission. The primary outcome was the expansion of ICH volume within the first 3 days between the study group and the control groups. Results: After implementing inclusion/exclusion criteria, 105 of 354 patients remained in the study. There were no significant differences in ICH volume on hospital days 2 and 3 between the groups. Admission factors including Glasgow coma scale score, hemoglobin level, ICH volume, and spot sign showed significant correlations in multivariate analysis. On the third day of hospitalization, admission serum magnesium levels showed a significant correlation with ICH expansion, whereas calcium levels did not. Conclusion Admission serum magnesium levels were found to correlate with hematoma expansion in patients with acute ICH. While magnesium itself may not be a direct therapeutic target, it could serve as a valuable indicator for identifying potential therapeutic strategies aimed at preventing ICH volume increase.

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: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background: The Korean National Cancer Screening Program (NCSP) for gastric cancer requires economic evaluation due to the low sensitivity of upper gastrointestinal series (UGIs) and the associated low cancer survival rate. This study aimed to ascertain the most cost-effective strategy for the NCSP. Methods: The hypothetical target population of this study was aged 40 years or older, and no actual participants were involved. Markov simulation models were constructed for 25 strategies, combinations of 1) screening methods (UGIs or endoscopy vs. endoscopy-only), 2) screening intervals (one, two, or three-year), and 3) upper age limit of screening (69, 74, 79 years old, or “no limit”). Costs, utility, and other input parameters were extracted from various databases and previous studies. Cost-utility, sensitivity, and scenario analyses were conducted. Results: The endoscopy-only strategy with a three-year interval with an upper age limit of 69 was the most cost-effective strategy with an incremental cost-utility ratio of KRW 13,354,106 per quality-adjusted life years. According to the probabilistic sensitivity analysis, the uncertainty of the result was significantly small. Scenario analysis is showed that as the screening rate increased, the endoscopy-only strategy saved more costs compared to the current NCSP. Therefore, it is important to maintain a high screening rate when altering the NCSP strategy. Conclusion Endoscopy-only screening was more cost-effective method than UGIs for the NCSP. Furthermore, a three-year interval with an upper-age limit of 69 years was the most cost-effective strategy. Efforts to improve cost-effective screening guidelines will support the efficient use of medical resources. Additionally, maintaining a higher screening rate may maximize the impact of the modification in strategy on cost-effectiveness.

Background: Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort. Methods: We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation. Results: Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465). Conclusion Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.

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: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: This study evaluated the practicability of the suicide rate reduction target set by the current national suicide prevention policy in Korea, the fifth Master Plan for Suicide Prevention (2023–2027). This policy aims to lower the suicide rate from 26/100,000 in 2021 to 18.2/100,000 by 2027. Methods: We utilized monthly suicide statistics data from 2011 onwards. Using Bayesian regression and Autoregressive Integrated Moving Average (ARIMA) models, we conducted interrupted time series analyses to estimate the effect of the previous policy, the National Action Plan for Suicide Prevention (2018–2022), on suicide rates. We assumed this as the additional suicide reduction expected from the current policy. We generated point predictions and simulations for suicide rates from 2023 to 2027 using Bayesian regression and ARIMA models. Results: The interrupted time series analyses did not reveal a significant reduction in suicides attributable to the previous policy. Point predictions from the two models indicated that the suicide rate would remain approximately 24/100,000 in 2027. Almost all of the simulations of the 2027 suicide rate did not meet the policy target of 18.2/100,000. Conclusion The findings suggest that the Korean government’s suicide rate reduction target for 2027 is likely unattainable based on current trends and the limited effectiveness of previous policies. The objectives of suicide prevention policies should be evidence-based, attainable, and accountable.