Purpose: Atypical hyperplasia (AH) management remains controversial due to variable malignant disease progression rates. While Western studies report 10% to 25% upgrade rates, data from Asian populations, particularly from referral academic centers, are limited. We aimed to identify predictive factors for malignant upgrade in Korean women with AH at academic hospitals. Methods: This retrospective multi-institutional study analyzed 340 patients diagnosed with AH on initial biopsy who underwent subsequent excision at five Korean academic hospitals from 2000 to 2022. Malignant upgrade was defined as ductal carcinoma in situ or invasive cancer on the final pathology. Multivariate logistic regression was used to identify independent predictors of upgrades. Results: Among 340 patients (319 atypical ductal hyperplasia, 20 atypical lobular hyperplasia, and 1 mixed), 128 (37.6%) experienced a malignant upgrade, 98 (76.6%) to ductal carcinoma in situ, and 30 (23.4%) to invasive cancer. In multivariate analysis, multifocal atypia (odds ratio [OR], 25.61; 95% confidence interval [CI], 11.20–58.55; P<0.001) and Breast Imaging-Reporting and Data System 4c-5 lesions (OR, 11.02; 95% CI, 1.43–84.86; P=0.021) were significant predictors. Multifocal atypia showed an 84.4% upgrade rate. Core needle biopsy had higher upgrade rates than vacuum-assisted biopsy (45.2% vs. 20.0%; P<0.001). The upgrade rates decreased from 50% to 25% over the study period (P<0.05). Conclusion The 37.6% upgrade rate in this tertiary referral cohort exceeded that in Western reports, with multifocal atypia emerging as the strongest predictor. These findings support immediate excision for multifocal atypia while allowing individualized management for unifocal lesions with favorable imaging in Korean tertiary care settings.

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.

Background: This study aimed to compare the intraoperative stability and early clinical outcomes of 40-mm diameter dual mobility (DM)-total hip arthroplasty (THA) with 36-mm ceramic head (large head) THA in active elderly patients with hip fractures. Methods: A prospective randomized controlled trial was conducted from May 2022 to December 2022. Inclusion criteria were as follows: age ≥ 60 years, displaced femoral neck fracture, Koval grade 1 or 2, planned 54-mm acetabular component, and over 1-year follow-up. Intraoperative stability tests were performed on all patients (internal rotation at 45°, 60°, and 90° of hip fracture). Functional outcomes (Harris Hip Score and University of California, Los Angeles [UCLA] Score) were evaluated at 6 weeks and 3 months postoperatively. Gait analysis using artificial intelligence (AI) techniques was conducted at 3 months postoperatively. Results: The study included 36 DM-THA patients (mean age, 69.6 ± 2.2 years; 44% women) and 37 large head THA patients (mean age, 69.6 ± 1.2 years; 64% women). No statistically significant differences were observed in functional outcomes and hip range of motion between the 2 groups. However, there was a significant difference in the gait speed and stance-swing phase of the large head THA group and the DM-THA group: the DM-THA group demonstrated superior gait speed (2.85 ± 0.83 kph vs. 2.04 ± 1.04 kph, p = 0.003) and higher stance phase ratios (operated side: 63.57% ± 3.82% vs. 48.19% ± 5.50%, p < 0.001; opposite side: 62.77% ± 2.27% vs. 49.93% ± 6.94%, p < 0.001). In the stability test at 90° of hip flexion, the DM-THA group had a measurement of 48.40° ± 5.17°, while the large head THA group had a measurement of 30.94° ± 2.98° (p = 0.012). Despite the lack of statistical significance, the intraoperative stability test showed the dislocation angle was notably different between the groups in the hip flexion position of 60° (51.60° ± 6.09° in the DM-THA group and 40.00° ± 2.80° in the large head THA group, p = 0.072). Conclusions Superior results were observed in the intraoperative stability test and early recovery of gait after DM-THA compared to large head THA. We believe that DM-THA can be a useful surgical option for THA in elderly patients with hip fractures.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Background: This study aimed to compare the intraoperative stability and early clinical outcomes of 40-mm diameter dual mobility (DM)-total hip arthroplasty (THA) with 36-mm ceramic head (large head) THA in active elderly patients with hip fractures. Methods: A prospective randomized controlled trial was conducted from May 2022 to December 2022. Inclusion criteria were as follows: age ≥ 60 years, displaced femoral neck fracture, Koval grade 1 or 2, planned 54-mm acetabular component, and over 1-year follow-up. Intraoperative stability tests were performed on all patients (internal rotation at 45°, 60°, and 90° of hip fracture). Functional outcomes (Harris Hip Score and University of California, Los Angeles [UCLA] Score) were evaluated at 6 weeks and 3 months postoperatively. Gait analysis using artificial intelligence (AI) techniques was conducted at 3 months postoperatively. Results: The study included 36 DM-THA patients (mean age, 69.6 ± 2.2 years; 44% women) and 37 large head THA patients (mean age, 69.6 ± 1.2 years; 64% women). No statistically significant differences were observed in functional outcomes and hip range of motion between the 2 groups. However, there was a significant difference in the gait speed and stance-swing phase of the large head THA group and the DM-THA group: the DM-THA group demonstrated superior gait speed (2.85 ± 0.83 kph vs. 2.04 ± 1.04 kph, p = 0.003) and higher stance phase ratios (operated side: 63.57% ± 3.82% vs. 48.19% ± 5.50%, p < 0.001; opposite side: 62.77% ± 2.27% vs. 49.93% ± 6.94%, p < 0.001). In the stability test at 90° of hip flexion, the DM-THA group had a measurement of 48.40° ± 5.17°, while the large head THA group had a measurement of 30.94° ± 2.98° (p = 0.012). Despite the lack of statistical significance, the intraoperative stability test showed the dislocation angle was notably different between the groups in the hip flexion position of 60° (51.60° ± 6.09° in the DM-THA group and 40.00° ± 2.80° in the large head THA group, p = 0.072). Conclusions Superior results were observed in the intraoperative stability test and early recovery of gait after DM-THA compared to large head THA. We believe that DM-THA can be a useful surgical option for THA in elderly patients with hip fractures.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.