Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.

Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model, experimental autoimmune encephalomyelitis (EAE). This study investigates the role of high mobility group box 1 (HMGB1) in oligodendrocyte precursor cells (OPCs) in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier (BBB) by using OPC-specific HMGB1 knockout (KO) mice. We found that HMGB1 released from OPCs promotes BBB disruption, subsequently allowing increased immune cell infiltration. The migration of CD4+ T cells isolated from EAE-induced mice was enhanced when co-cultured with OPCs compared to oligodendrocytes (OLs). OPC-specific HMGB1 KO mice exhibited lower BBB permeability and reduced immune cell infiltration into the CNS, leading to less damage to the myelin sheath and mitigated EAE progression. CD4+ T cell migration was also reduced when co-cultured with HMGB1 knock-out OPCs. Our findings reveal that HMGB1 secretion from OPCs is crucial for regulating immune cell infiltration and provides insights into the immunomodulatory function of OPCs in autoimmune diseases.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; HMGB1 Protein/deficiency* ; Mice, Knockout ; Oligodendrocyte Precursor Cells/immunology* ; Mice, Inbred C57BL ; CD4-Positive T-Lymphocytes/immunology* ; Cell Movement ; Blood-Brain Barrier/immunology* ; Mice ; Myelin Sheath/pathology* ; Disease Models, Animal ; Coculture Techniques ; Oligodendroglia/metabolism* ; Female ; Cells, Cultured

Background/Aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE.Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established.This study aims to establish these thresholds for the first time among Asian patients with EoE. Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 andNovember 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology wereavailable for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold(sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). Conclusions The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3,respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Background/Aims: Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H.pylori eradication. Methods: Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50–59 years), group 3 (60–69years), and group 4 (≥70 years). Results: All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12).After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57). Conclusions The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.