Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

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: In Korea, the patterns of prevalence of gynecological cancers have shifted due to rising obesity-related cancer cases. We evaluated the associations of body mass index (BMI) and waist circumference (WC) with the risk of gynecological malignancy in Korean women. Methods: Using National Health Insurance Service cohort data, we analyzed 365,581 participants among the 1,999,980 women aged ≥ 19 years who underwent health check-ups at the baseline year 2009–2010, excluding those who died, those with prior cancer diagnoses, underwent hysterectomy and/or salpingo-oophorectomy before the index date (January 1st, 2011), or missing/outliers BMI and WC values. Follow-up extended to December 31st, 2021, evaluating the incidences of endometrial, ovarian, and cervical cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) for each gynecological malignancy according to BMI and WC were calculated using Cox proportional hazard regression. Results: Among the 365,581 participants, 898, 1,268, and 873 cases of endometrial, ovarian, and cervical cancer occurred, respectively. HRs (95% CIs) for endometrial cancer were 1.37 (1.15–1.63), 1.63 (1.38–1.94), and 3.64 (2.81–4.70) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend < 0.001). HRs (95% CIs) for ovarian cancer were 1.16 (1.00–1.33), 1.19 (1.03–1.37), and 1.49 (1.12–1.98) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend = 0.002). No significant association was found between BMI and the risk for cervical cancer (P for trend = 0.266). HRs (95% CIs) for endometrial cancer were 1.35 (1.09–1.66), 1.41 (1.14–1.74), and 1.90 (1.55–2.34) for the 2nd, 3rd, and 4th quartiles of WCs compared to the 1st quartile (P for trend <0.001). Ovarian cancer tended to increase and cervical cancer tended to decrease as WC increased (P for trend = 0.035 for ovarian cancer, P for trend = 0.034 for cervical cancer). Conclusion In Korean women, the risks of endometrial and ovarian cancers increased significantly from the pre-obese level as BMI and WC increased, while cervical cancer risk tended to increase as WC decreased. Management of obesity should be reinforced for the prevention of obesity-related gynecological cancers, considering the increasing incidence of these cancers among Korean women.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

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: In Korea, the patterns of prevalence of gynecological cancers have shifted due to rising obesity-related cancer cases. We evaluated the associations of body mass index (BMI) and waist circumference (WC) with the risk of gynecological malignancy in Korean women. Methods: Using National Health Insurance Service cohort data, we analyzed 365,581 participants among the 1,999,980 women aged ≥ 19 years who underwent health check-ups at the baseline year 2009–2010, excluding those who died, those with prior cancer diagnoses, underwent hysterectomy and/or salpingo-oophorectomy before the index date (January 1st, 2011), or missing/outliers BMI and WC values. Follow-up extended to December 31st, 2021, evaluating the incidences of endometrial, ovarian, and cervical cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) for each gynecological malignancy according to BMI and WC were calculated using Cox proportional hazard regression. Results: Among the 365,581 participants, 898, 1,268, and 873 cases of endometrial, ovarian, and cervical cancer occurred, respectively. HRs (95% CIs) for endometrial cancer were 1.37 (1.15–1.63), 1.63 (1.38–1.94), and 3.64 (2.81–4.70) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend < 0.001). HRs (95% CIs) for ovarian cancer were 1.16 (1.00–1.33), 1.19 (1.03–1.37), and 1.49 (1.12–1.98) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend = 0.002). No significant association was found between BMI and the risk for cervical cancer (P for trend = 0.266). HRs (95% CIs) for endometrial cancer were 1.35 (1.09–1.66), 1.41 (1.14–1.74), and 1.90 (1.55–2.34) for the 2nd, 3rd, and 4th quartiles of WCs compared to the 1st quartile (P for trend <0.001). Ovarian cancer tended to increase and cervical cancer tended to decrease as WC increased (P for trend = 0.035 for ovarian cancer, P for trend = 0.034 for cervical cancer). Conclusion In Korean women, the risks of endometrial and ovarian cancers increased significantly from the pre-obese level as BMI and WC increased, while cervical cancer risk tended to increase as WC decreased. Management of obesity should be reinforced for the prevention of obesity-related gynecological cancers, considering the increasing incidence of these cancers among Korean women.