Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Background: Preeclampsia (PE) is a hypertensive pregnancy disorder linked to placental dysfunction, often involving pathological lesions like acute atherosis, decidual vasculopathy, accelerated villous maturation, and fibrinoid deposition. However, there is no gold standard for the pathological diagnosis of PE and this limits the ability of clinicians to distinguish between PE and non-PE pregnancies. Recent advances in computational pathology have provided the opportunity to automate pathological analysis for diagnosis, classification, prediction, and prediction of disease progression. In this study, we assessed whether computational pathology could be used to identify PE placentas. Methods: A total of 168 placental whole-slide images (WSIs) of patients from Seoul National University Hospital (comprising 84 PE cases and 84 normal controls) were used for model development and internal validation. For external validation of the model, 76 placental slides (including 38 PE cases and 38 normal controls) were obtained from the Boramae Medical Center (BMC). To establish standard criteria for diagnosing PE and distinguishing it from controls using placental WSIs, patch characteristics and quantification of terminal and intermediate villi were employed. In unsupervised learning, K-means clustering was conducted as a feature obtained through an Auto Encoder to extract the ratio of each cluster for each WSI. For supervised learning, quantitative assessments of the villi were obtained using a U-Net-based segmentation algorithm. The prediction model was developed using an ensemble method and was compared with a clinical feature model developed by using placental size features. Results: Using ensemble modeling, we developed a model to identify PE placentas.The model showed good performance (area under the precision-recall curve [AUPRC], 0.771; 95% confidence interval [CI], 0.752–0.790), with 77.3% of sensitivity and 71.1% of specificity, whereas the clinical feature model showed an AUPRC 0.713 (95% CI, 0.694–0.732) with 55.6% sensitivity and 86.8% specificity. External validation of the predictive model employing the BMC-derived set of placental slides also showed good discrimination (AUPRC, 0.725; 95% CI, 0.720–0.730). Conclusion The proposed computational pathology model demonstrated a strong ability to identify preeclamptic placentas. Computational pathology has the potential to improve the identification of PE placentas.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). Conclusions After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Background/Aims: Helicobacter pylori (H. pylori) infection highly correlates with erythematous/exudative gastritis, which is one of the endoscopic findings of the Sydney classification system. The present study aimed to evaluate the association between endoscopic severity of erythematous/exudative gastritis and H. pylori infection. Methods: We prospectively enrolled asymptomatic adults who were diagnosed with erythematous/exudative gastritis during screening esophagogastroduodenoscopy. A rapid urease test was performed in all participants to diagnose H. pylori infection. The severity of erythematous/exudative gastritis was determined based on the Sydney classification system. Two investigators independently evaluated the endoscopic findings. The primary endpoint was H. pylori infection rate according to the severity of erythematous/exudative gastritis (mild vs. moderate-to-severe). Results: A total of 177 patients with erythematous/exudative gastritis were included. The rate of H. pyloriinfection was 86.4% in all patients. Of 177 included patients, 78 were at mild degree, 48 were at moderate degree, and 51 were at severe degree. The inter-observer variation was 4.6% and kappa value was 0.593. H. pylori infection rate was similar between patients with mild erythematous/exudative gastritis and those with moderate-to-severe erythematous/exudative gastritis (91.0% vs. 82.8%, p=0.115). Even after adjusting potential confounding variables, the severity of erythematous/exudative gastritis was not associated with H. pylori infection rate. Conclusions H. pylori infection is commonly observed in patients with erythematous/exudative gastritis. However, the severity of erythematous/exudative gastritis is not associated with H. pylori infection rate.

40 years or new hires with less than 1 year of service.]]>
Brain ; Cardiovascular Diseases ; Cohort Studies ; Firefighters ; Follow-Up Studies ; Health Surveys ; Hospitals, University ; Humans ; Killer Cells, Natural ; Korea ; Magnetic Resonance Imaging ; Mental Disorders ; Mental Health ; Neuropsychological Tests ; Polycyclic Hydrocarbons, Aromatic ; Prospective Studies ; Republic of Korea ; Risk Factors

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. It results from disproportionate blood supply to each fetus caused by abnormal vascular anastomosis within the placenta. Amniotic fluid (AF) is an indicator reflecting the various conditions of the fetus, and an imbalance in AF volume is essential for the antenatal diagnosis of TTTS by ultrasound. In this study, two different mass spectrometry quantitative approaches were performed to identify differentially expressed proteins (DEPs) within matched pairs of AF samples.METHODS: We characterized the AF proteome in pooled AF samples collected from donor and recipient twin pairs (n = 5 each) with TTTS by a global proteomics profiling approach and then preformed the statistical analysis to determine the DEPs between the two groups. Next, we carried out a targeted proteomic approach (multiple reaction monitoring) with DEPs to achieve high-confident TTTS-associated AF proteins.RESULTS: A total of 103 AF proteins that were significantly altered in their abundances between donor and recipient fetuses. The majority of upregulated proteins identified in the recipient twins (including carbonic anhydrase 1, fibrinogen alpha chain, aminopeptidase N, alpha-fetoprotein, fibrinogen gamma chain, and basement membrane-specific heparan sulfate proteoglycan core protein) have been associated with cardiac or dermatologic disease, which is often seen in recipient twins as a result of volume overload. In contrast, proteins significantly upregulated in AF collected from donor twins (including IgGFc-binding protein, apolipoprotein C-I, complement C1q subcomponent subunit B, apolipoprotein C-III, apolipoprotein A-II, decorin, alpha-2-macroglobulin, apolipoprotein A-I, and fibronectin) were those previously shown to be associated with inflammation, ischemic cardiovascular complications or renal disease.CONCLUSION: In this study, we identified proteomic biomarkers in AF collected from donor and recipient twins in pregnancies complicated by TTTS that appear to reflect underlying functional and pathophysiological challenges faced by each of the fetuses.