PURPOSE: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set—T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

Choi HJ, et al. Korean Circ J. 2025 Apr;55:e63. https://doi.org/10.4070/kcj.2024.0381

INTRODUCTION: The association between postpolypectomy bleeding (PPB) and thrombocytopenia remains unclear, and current evidence is insufficient to provide definitive guidelines for managing patients with thrombocytopenia undergoing endoscopic procedures. We assessed the association between thrombocytopenia and PPB to identify the minimum platelet count threshold for safe colonoscopic polypectomy. METHODS: This large cohort study included patients who had undergone colonoscopy and polypectomy in Korea between 2005 and 2022. A wide range of covariates, including patient-related, polyp-related, and procedure-related factors, were collected. We identified the optimal platelet cutoff value of 90,000/μL using the Youden Index method and conducted propensity score matching and inverse probability of treatment weighting analyses to determine the effect of thrombocytopenia on PPB risk. RESULTS: Overall, 21,562 patients were screened, including 16,852 individuals and 41,930 polyps. Among these patients, 198 (1.2%) had platelet counts <90,000/μL, and 16,654 (98.8%) had platelet counts ≥90,000/μL. After propensity score matching, patients with platelet counts 20 mm), the optimal platelet count threshold was identified as 100,000/μL for safe colonoscopic polypectomy. The results obtained using inverse probability of treatment weighting were consistent. DISCUSSION: Patients with platelet counts <90,000/μL exhibited significantly elevated rates of immediate PPB and delayed PPB, suggesting that maintaining platelet levels above this threshold may be crucial for ensuring the safety of colonic polypectomy.

Neurological involvement in Kawasaki disease (KD) is rare and ranges from mild to severe, occasionally leading to fatal outcomes and poor prognosis. However, its impact on clinical outcomes, particularly coronary artery involvement, remains unclear. This study aimed to investigate neurological manifestations during the acute phase of KD and evaluate their clinical implications, focusing on treatment resistance and coronary complications. We analyzed data from the Health Insurance Review and Assessment Service of the Republic of Korea between 2007 and 2022 for patients under 18 years of age diagnosed with KD (ICD-10 code M30.3). Neurological manifestations, ranging from mild and nonspecific symptoms to severe complications, were evaluated. Among 95,648 patients with KD, neurological manifestations occurred in 4319 (4.51 %), comprising 4540 events. The most common symptoms were febrile seizures (2.40 %), followed by meningitis/aseptic meningitis, headache, seizures, epilepsy, meningoencephalitis, irritability, brain hemorrhage, facial nerve palsy, and cerebral infarction or stroke. There were no significant differences in age or sex distribution between those with and without neurological manifestations, although prevalence was highest in patients >5 years. Neurological manifestations were more frequent in summer and were associated with longer hospital stays (p < 0.001), more frequent use of multiple intravenous immunoglobulin (IVIG) treatments (p < 0.001), and higher transfer and mortality rates (p < 0.001). However, no significant differences were observed in coronary interventions or adjunctive therapy use (aspirin, warfarin, steroids, and infliximab). Neurological manifestations in KD were associated with more frequent IVIG resistance, but showed no significant association with coronary outcomes.

Background: The association between delayed post‐polypectomy bleeding and chronic kidney disease remains unclear. Objective: This study investigated whether patients with chronic kidney disease are at an increased risk of delayed post‐polypectomy bleeding. Methods: This cohort study included patients who underwent colonoscopy and polypectomy in Korea between 2005 and 2022. We assessed various covariates, including patient‐, polyp‐, and procedure‐related factors, using propensity score matching and inverse probability of treatment weighting to determine the impact of chronic kidney disease on delayed post‐polypectomy bleeding risk. Results: Out of 21,562 patients, 16,591 with 41,014 polyps were included in the analysis. Of these, 2057 (12.4%) had chronic kidney disease, with 894 in early‐stage (stages 1 and 2) and 1163 in advanced‐stage (stages 3–5). There were 14,534 individuals without chronic kidney disease. After propensity score matching, the risk of delayed post‐polypectomy bleeding in patients with chronic kidney disease was significantly higher than that in the non‐chronic kidney disease group (OR 1.80, CI 1.12–2.89, p = 0.01). The risk increased with chronic kidney disease stage (OR 2.38, 95% CI 1.01–5.64 for early stage; OR 2.80, 95% CI 1.20–6.51 for advanced stage, all p < 0.05). The results remained robust after inverse probability analysis. Conclusions: Chronic kidney disease is an independent risk factor for delayed post‐polypectomy bleeding, even in the early stages. The risk correlates with the chronic kidney disease stage. Meticulous attention is imperative during polypectomy for all patients with chronic kidney disease, including those in the early stages.

We aimed to elucidate whether proton pump inhibitor (PPI) users are at increased risk of gastric cancer compared with non-PPI users or histamine-2 receptor antagonist (H2RA) users. A population-based cohort study was conducted using data from the UK Biobank from 1990 to 2016. We compared the incidence of gastric cancer after a minimum of 1-year drug exposure between PPI users and non-PPI or H2RA users using Cox proportional hazards models. Secondary analyses assessed the duration and dose-response associations. Sensitivity analyses incorporating various matching ratios, extended lag periods, and propensity score stratification were performed. After large-scale propensity score matching, we included 42,732 new PPI users, 42,732 non-PPI users, and 4,762 new H2RA users. During a median follow-up of 6.7 years, PPI users had a 2.32-fold higher risk of gastric cancer than non-PPI users (hazard ratio [HR], 2.324; 95% confidence interval [CI], 1.646 to 3.282), with numbers needed to harm of 488 and 442 at 2 and 4 years, respectively. Compared with H2RA users, PPI users also had a significantly higher incidence of gastric cancer (HR, 5.343; 95% CI, 1.557 to 18.335). The risk of gastric cancer tended to increase with a longer cumulative duration of PPI use and higher cumulative doses of PPIs. Moreover, these results remained robust after adjustments for various lag periods, matching ratios, and propensity score stratification. PPI use was associated with a higher incidence of gastric cancer, albeit with a low absolute risk. Therefore, long-term PPI use should be considered cautiously, even in regions with a low risk of gastric cancer.