Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Topical hemostatic powders may help limit blood loss when applied to a wound early in the course of bleeding. This study evaluated the effectiveness and safety of a hemostatic powder composed of carboxymethyl starch and calcium ions for reducing hemorrhagic complications (specifically hemoglobin loss) after transrectal prostate biopsy. Materials and Methods: In this randomized controlled trial, 95 patients undergoing transrectal prostate biopsy received either hemostatic powder with povidone-iodine–soaked gauze or povidone-iodine–soaked gauze alone. The primary outcome was hemoglobin level measured before biopsy and 1 day after biopsy. Secondary outcomes included the incidence of hematuria, hematochezia, infection, and other complications. Results: Postbiopsy hemoglobin levels did not differ significantly between the control (12.3±1.6 g/dL) and experimental (12.2±1.8 g/dL) groups (p=0.872). In both groups, hemoglobin level decreased significantly from 13.1±1.9 g/dL before biopsy to 12.2±1.8 g/dL after biopsy (p<0.001). Hematuria occurred in 95.1% of the experimental group and 87.2% of the control group (p=0.389). The incidence of hematochezia was significantly lower in the experimental group (18.8%) than in the control group (59.6%) (p<0.001). No significant differences were observed in other complications, including infection, urinary retention, and transfusion requirement. No severe adverse events were reported in either group. Conclusion Application of the hemostatic powder did not prevent postbiopsy hemoglobin decline; however, it significantly reduced the incidence of hematochezia. The procedure appeared safe in this trial, although further studies are needed to identify more effective strategies to prevent cumulative hemoglobin loss after transrectal prostate biopsy.

Background: Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are effective treatments for non-small cell lung cancer (NSCLC), but their use can lead to severe pneumonitis. This study aims to evaluate the utility of Krebs von den Lungen-6 (KL-6) for predicting and diagnosing PD-1/PD-L1 inhibitor-related pneumonitis in NSCLC patients. Methods: We conducted a prospective observational study at a university-affiliated tertiary hospital in Korea from February 2022 to June 2023. Baseline KL-6 levels were measured immediately before initiating PD-1/PD-L1 inhibitor therapy. In patients who developed pneumonitis, KL-6 levels were monitored every 1–2 weeks from the onset of pneumonitis. For patients without pneumonitis, KL-6 levels were measured every 6 weeks. We compared clinical characteristics and serial KL-6 levels between the pneumonitis and non-pneumonitis groups. Results: Eighteen patients were enrolled, with 11 developing pneumonitis. Baseline KL-6 levels did not significantly differ between the two groups (261 U/mL in the pneumonitis group vs. 373 U/mL in the non-pneumonitis group, p=0.375). In the pneumonitis group, KL-6 levels generally showed an upward trend, with a median of 412 U/mL at pneumonitis onset. Conversely, KL-6 levels in the non-pneumonitis group showed no clear overall change. Conclusion In this pilot study, baseline KL-6 was not clearly linked to PD-1/PD-L1 inhibitor-related pneumonitis in NSCLC patients. However, increases in KL-6 levels post-baseline were more frequently observed in patients who developed pneumonitis, including cases of all-cause pneumonitis.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

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.