Background: and Purpose Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods: Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine–Gray subdistribution hazard model with time-varying covariates. Results: Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17–4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77–1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post–GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17–0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.

Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

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.

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: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Background: s/Aims: In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy. Methods: CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns. Results: Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR). Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background: The diagnosis of tuberculous pleural effusion (TPE) often relies on pleural fluid adenosine deaminase (ADA) levels. The diagnostic utility of ADA, however, is influenced by the prevalence of tuberculosis (TB) in local populations. Malignant pleural effusion (MPE) cases can exhibit moderately elevated ADA levels comparable to those seen in TPE. As population aging potentially impacts ADA levels, global TB incidence is decreasing whereas the burden of malignancy is on the rise. Consequently, epidemiological shifts and temporal changes in ADA distribution complicate the differential diagnosis between TPE and MPE when ADA levels are within the 40–70 IU/L range. Nonetheless, data specific to this subset are scarce. Methods: This retrospective study included consecutive patients aged > 18 years with confirmed TPE and MPE, spanning from 2012 to 2023. ADA levels in pleural fluid were categorized into three groups: < 40 IU/L, 40–70 IU/L, and > 70 IU/L. The study examined annual trends in the frequency of new cases and ADA level distributions over time and identified discriminating factors between TPE and MPE in cases with ADA levels of 40–70 IU/L. Results: In total, 297 TPE and 369 MPE cases were included in this study. Over the study period, the frequency of TPE progressively declined, while that of MPE increased. In the most recent four-year period, new TPE and MPE cases with ADA levels of 40–70 IU/L occurred at comparable numbers. Multivariable analysis identified pleural fluid carcinoembryonic antigen (CEA) levels and the number of focal pleural nodules as independent predictors for MPE. Specifically, the presence of either CEA levels > 15.7 ng/mL or more than eight pleural nodules yielded the highest diagnostic accuracy with a sensitivity of 88%, specificity of 100%, and an area under the curve of 0.95. Conclusion The differential diagnosis between TPE and MPE with pleural ADA levels of 40–70 IU/L has become increasingly critical due to evolving epidemiological patterns and ADA distribution changes over time. Pleural fluid CEA levels and the characteristics of pleural nodules may offer valuable guidance in distinguishing between TPE and MPE within this diagnostic gray zone.