Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

Accurate and early identification of stroke and large vessel occlusion (LVO) in emergency settings is essential for improving patient outcomes and ensuring the efficient allocation of medical resources. This clinical practice guideline systematically reviews domestic and international literature and conducts meta-analyses to evaluate the utility and diagnostic accuracy of stroke assessment tools used in prehospital emergency medical services (EMS). We developed a guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted to evaluate the usefulness of diagnostic EMS assessment tools for diagnosing stroke and LVO. Overall, 70 non-randomized control studies were selected for this study. A meta-analysis was conducted with a subgroup analysis to distinguish between patients with stroke and those with LVO. EMS tools demonstrated high sensitivity but low specificity for diagnosing stroke. In the prehospital setting, using validated EMS stroke assessment tools is recommended for the early identification of stroke and LVO. Upon hospital arrival, stroke specialists should conduct further evaluation and triage to confirm the diagnosis and guide appropriate management. Delays in diagnosing LVO are frequently unacceptable. While experts advocate for the use of EMS assessment tools to facilitate early identification of LVO, these tools alone lack adequate sensitivity. Therefore, further diagnostic evaluations and consultation with stroke specialists upon hospital arrival are recommended.

The mothership (MS) model, where patients are directly transferred to a thrombectomy-capable center, and the drip-and-ship (DS) model, where thrombolysis is initiated at the nearest primary stroke center before transfer for thrombectomy, are the primary transport modes for patients with stroke. We aimed to establish guidelines for selecting the appropriate transfer strategy based on emergent large vessel occlusion (LVO). We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer three Population, Intervention, Comparison, and Outcome questions comparing MS and DS models. The risk of bias was assessed using the Newcastle-Ottawa Scale. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcomes, mortality, and successful recanalization. Twenty-six non-randomized controlled studies showed that the MS model improved good functional outcomes by approximately 14% compared with the DS model (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.00–1.30). Fifteen studies reported that mortality in the MS and DS models showed no significant differences (OR, 0.97; 95% CI, 0.84–1.11). Twenty-four studies revealed no significant difference in successful recanalization between the MS and DS models (OR, 0.87; 95% CI, 0.68–1.10). The MS model should be considered first to improve the functional outcome of patients with LVO. However, if thrombectomy cannot be performed immediately after thrombolysis, or if a thrombectomy-enabled hospital is not nearby, the DS model should be considered by stroke specialists depending on transportation time and regional factors. We suggest a mixed approach with the DS model based on specific circumstances or regions to ensure the optimum treatment of patients with acute ischemic stroke (AIS). Appropriate transport for patients with LVO improves the prognosis of AIS.

Purpose: Bronchiolitis obliterans syndrome (BOS) can develop as a manifestation of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and may ultimately require lung transplantation (LT). However, reports on LT outcomes for BOS after allo-HSCT are limited. This study aimed to compare the outcomes of LT for BOS following allo-HSCT with those for idiopathic pulmonary fibrosis (IPF). Materials and Methods: A total of 487 patients underwent LT between January 2010 and August 2023. Among them, the baseline characteristics and outcomes of 35 patients with BOS following allo-HSCT and 216 patients with IPF were analyzed. Results: The BOS group was younger and had a lower body mass index (BMI) compared to the IPF group (33.7±11.9 years vs.59.7±7.3 years, p<0.001; 17.6±3.7 kg/m2 vs. 22.0±3.6 kg/m2 , p<0.001, respectively). The proportion of male patients was lower in the BOS group than in the IPF group (54.3% vs. 84.3%, p<0.001). Preoperative ventilator support was more common in the BOS group compared to the IPF group (62.9% vs. 32.4%, p=0.001). In Kaplan–Meier survival analysis, the 5-year survival rate was significantly higher in the BOS group than in the IPF group (71.0% vs. 44.9%, p=0.022). In the Cox proportional hazards model, age was the only factor significantly associated with survival [hazard ratio (95% confidence interval): 1.04 (1.02–1.07), p<0.001]. Conclusion The survival rate of the BOS group was not inferior to that of the IPF group after adjusting for sex, age, and BMI. Therefore, LT should be actively considered as a treatment option for patients with BOS following allo-HSCT.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Background: To assess the mediation effect of gestational weight gain (GWG) and blood heavy metal levels in the late pregnancy affecting the association between early pregnancy metal exposure and fetal growth. Methods: We analyzed data from Korean Children’s Environmental Health Study cohort comprising 4,712 full-term births. Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy, and newborn birthweights were retrieved. We applied single-exposure model to assess the association between heavy metal levels and newborn anthropometric measures and conducted path analyses to examine the direct and indirect effects of heavy metal levels in early pregnancy on newborn measures. Results: Exposure to Pb (β = −15.470, P = 0.036) and Cd (β = −24.150, P = 0.004) during late pregnancy were associated with lower birthweight. Early exposure to Pb was not directly associated with lower birthweight, however, mediation of late exposure to Pb (β = −7.417, P = 0.049) resulted in lower birthweight (β = −14.787, P = 0.036). Early exposure to Hg was associated with higher birthweight, however, indirect paths via GWG (β = 3.626, P = 0.048) and late Hg levels (β = −12.929, P = 0.111) countered each other, resulting in the nullification of the total effect (β = −8.519, P = 0.301). Conclusion The effect of Pb exposure in early pregnancy on birthweight was mediated by GWG and Pb exposures during late pregnancy. When assessing the impact of heavy metal exposure on birthweight, it is important to note that GWG and late heavy metal levels act as mediators, rather than confounders.

Background: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in children, with a rising incidence of macrolide resistance. Early diagnosis is crucial for reducing the disease burden; however, current diagnostic tools have limitations.We evaluated the diagnostic accuracy of serological assays and their performance based on symptom onset in children with CAP. Methods: From September 2023 to September 2024, we prospectively enrolled children with CAP, classified as M. pneumoniae pneumonia (MPP) or non-MPP, from 16 hospitals in Korea. Serological testing included chemiluminescence immunoassay (CLIA) and ELISA for detecting IgM and IgG, along with particle agglutination (PA) for total antibody measurements. Serological responses were analyzed at different times after symptom onset (0–4, 5–9, and 10–21 days). Results: Among 472 children with CAP (362 MPP, 110 non-MPP), 138 (29.2%) underwent PA testing, and 334 (70.8%) underwent IgM testing. PA at a 1:640 cutoff showed 48.0% sensitivity and 100% specificity. CLIA and ELISA showed comparable sensitivities (69.1% vs. 69.2%) and specificities (76.9% vs. 66.7%) for IgM testing. Seropositivity increased significantly with time since symptom onset (P for trend < 0.001), reaching 97.9% for IgM, 62.5% for IgG, and 94.7% for PA at 10–21 days. Conclusions The time post-symptom onset significantly influenced the diagnostic utility of serological tests for pediatric MPP, which showed limited value during the early stage of illness. These findings emphasize the importance of symptom onset-based interpretation of serological test results and their utility in complementing PCR when optimizing MPP diagnosis in children.

Background: Cancer cell line-derived feeder cells enhance natural killer (NK) cell expansion; however, concerns regarding viable residual feeder cells in the final product limit their use. Evidence supporting the safety of NK-sensitive K562-based feeders, even when irradiated, is scarce. We optimized an NK cell expansion protocol using genetically engineered K562-mbIL-18/-21 (GE-K562) feeder cells and clinical-grade media and confirmed the absence of residual feeder cells. Methods: NK cell expansion efficiency was compared between feeder-free and feederbased systems using CTS NK-Xpander Medium. To achieve optimal NK expansion, various peripheral blood mononuclear cell (PBMC)-to-feeder ratios and re-stimulation frequencies were tested over 21 days. Flow cytometry and BCR::ABL1 quantitative reverse transcription PCR (RT-qPCR) were used to confirm the absence of feeder cells in the final NK cell product. Results: Feeder-based systems showed superior NK cell fold expansion compared with that of feeder-free systems. Among feeder-based conditions, NK cells expanded 5,224-fold at a 2:1 PBMC-to-feeder ratio after 3 weeks, relative to 1,450-fold at a 6:1 ratio (P < 0.05).Re-stimulation on days 7 and 14 further increased expansion up to 261,457-fold. Irradiated feeder cells showed no proliferation and were eliminated within 3–6 days. On day 21, flow cytometry and BCR::ABL1 RT-qPCR results confirmed the absence of residual feeder cells. Conclusions Our optimized NK cell expansion protocol using irradiated GE-K562 feeder cells and clinical-grade media offers a safe and scalable approach to generating large numbers of NK cells, supporting its potential use in clinical immunotherapy applications.

BACKGROUND/OBJECTIVES: Dietary supplement use is common among breast cancer survivors, but studies on Asian populations remain limited. This study investigated dietary supplement use among Korean breast cancer survivors, distinguishing between vitamin/ mineral (VM) and non-vitaminon-mineral (NVNM) supplements. SUBJECTS/METHODS: This cross-sectional study included 1,136 stage I–III breast cancer survivors from 12 Korean hospitals, who survived more than 6 mon post-surgery. The participants completed a questionnaire on post-diagnostic dietary supplement use. Stepwise logistic regression was applied, calculating odds ratios (ORs) and 95% confidence intervals (CIs) to identify the demographic and clinical factors associated with VM and NVNM use. RESULTS: Seventy percent of survivors reported supplement use, with 25% using a single product. The most common VM supplements were multivitamins/minerals, vitamin D, and vitamin C, while the most common NVNM supplements included omega-3 fatty acids, probiotics, and ginseng. Survivors with higher education and greater physical activity were more likely to use VM supplements (ORs [95% CIs], 2.74 [1.76–4.25] for college graduates or above vs. middle school or below; 1.38 [1.02–1.88] for the most active group vs. the least active group). NVNM use was associated with higher education, greater physical activity levels, and a history of smoking (ORs [95% CIs], 2.29 [1.46–3.58] for college graduates or above vs. middle school or below; 1.52 [1.13–2.06] for the most active group vs. the least active group; 2.00 [1.23–3.25] for ever smokers vs. never smokers). Survivors who had undergone chemotherapy were also more likely to use NVNM supplements than those who had not (OR [95% CI], 1.37 [1.02–1.84]). CONCLUSION Seventy percent of Korean breast cancer survivors used dietary supplements in this study. VM use was associated with higher education and physical activity, while higher NVNM use was associated with higher education, greater physical activity, a history of smoking, and chemotherapy.