The ONCO DVT study demonstrated the benefit of extended anticoagulation therapy with edoxaban in patients with cancer-associated isolated distal deep vein thrombosis (DVT). However, it remains unclear whether these results can be applied regardless of the number of thrombosed venous segments. In this post-hoc subgroup analysis of the ONCO DVT study, 601 patients were stratified into the single-site (N=268) and multiple-sites (N=333) DVT subgroups based on the number of thrombosed venous segments at diagnosis. We compared 12-month and 3-month edoxaban treatment groups in each subgroup for the primary endpoint of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death and the major secondary endpoint of major bleeding at 12 months. The cumulative 12-month incidence of the primary endpoint was significantly lower in the 12-month edoxaban group than in the 3-month edoxaban group both in the single-site (0.8
Gastric cancer remains a significant health burden, especially in Asia. Potassium-competitive acid blockers (P-CABs) provide stronger acid suppression than proton pump inhibitors (PPIs), but their long-term impact on metachronous gastric cancer (MGC) remains unclear. This study evaluated the incidence and duration-dependent risk of MGC in P-CAB/PPI users. This multicenter retrospective cohort study included patients from 15 institutions in Japan who underwent endoscopic or surgical resection for gastric cancer between 2014 and 2022. After exclusions, 7172 patients who had received H. pylori eradication were analyzed. Chronic use of P-CAB/PPI was defined as administration for more than 3 months. The primary outcome was the incidence of MGC. Cox regression models were used, along with subgroup analyses based on duration and initial treatment type (endoscopy versus surgery). During a median follow-up of 5.8 years, MGC developed in 342 patients. The incidence was highest among P-CAB users (20.9 per 1,000 person-years), followed by PPI users (13.5) and non-users (7.1). Both P-CAB and PPI use were independently associated with increased MGC risk (hazard ratio 3.89 and 1.75, respectively). The association between P-CAB use and MGC was stronger with longer durations of use (hazard ratio 3.44 for < 1 year, 3.95 for 1–3 years, and 9.36 for > 3 years) and was particularly evident in the post-endoscopic group (hazard ratio 4.22) in subgroup analyses. Chronic use of P-CAB/PPI were associated with MGC. Longer duration may be associated with increased risk of MGC. Further studies are warranted to validate these findings.
Rationale Conventional monitoring of acute respiratory distress syndrome (ARDS) relies on global parameters, eg, tidal volume, airway pressure, and driving pressure. These parameters do not capture regional stress heterogeneity within the lung.Objectives To develop and validate a novel technique, lung stress mapping visualizing regional lung stress throughout the lung, and to evaluate its biological and clinical relevance.Methods Lung stress mapping combines esophageal pressure and plateau pressure with CT-derived pleural pressure gradients to generate spatially resolved maps of inspiratory transpulmonary pressure. Accuracy was tested in pigs by surgically inserted pleural sensors. Biological relevance was assessed in rabbits by correlating lung stress mapping-derived parameters with regional proinflammatory cytokine expression. Clinical feasibility and associations with outcome were evaluated in 20 consecutive ARDS patients enrolled in a prospective study.Measurements and Main Results Good correlation and agreement between sensor-derived and mapping-derived lung stress were confirmed. In rabbits, lung inflammation predominantly occurred in nondependent lung regions where lung stress was higher, and overall inflammation correlated with lung stress mapping-derived parameters. In ARDS patients, all received lung-protective ventilation. Non-survivors had significantly higher lung stress mapping-derived maximum and mean lung stress than survivors, despite similar global ventilatory parameters. Exploratory ROC analyses showed stronger associations of lung stress mapping-derived parameters with 90-day mortality than driving pressure.Conclusions Lung stress mapping accurately quantified regional transpulmonary stress and revealed biologically and clinically meaningful heterogeneity. This technique may help identify patients with ARDS at increased risk of ventilator-induced lung injury who would not be recognized through conventional respiratory monitoring.
Self-expandable metallic stents (SEMSs) are widely used for palliation of malignant esophageal strictures and esophago-respiratory fistulas. As longer survival is achieved with contemporary systemic therapy, late complications, particularly stent obstruction, are increasingly reported. We evaluated the outcomes and late complications of stent placement, focusing on obstruction. This single-center, retrospective cohort study included patients who underwent SEMS placement for malignant esophageal strictures or fistulas between February 2009 and February 2024. Dysphagia severity and oral intake were assessed using dysphagia scores, and adverse events were recorded. Patients with or without obstruction were compared. Among the 103 included patients (median age: 74 years, 76
BACKGROUND: Tertiary lymphoid structures (TLSs) maturity and cellular composition shape resistance or sensitivity to immune-checkpoint blockade (ICB) across cancers. Single-cell spatial resolution data for the endothelial compartment of TLSs are lacking; therefore, we investigated the cellular composition, endothelial dynamics, and cell-cell interactions within TLS regions. METHODS: We applied high-resolution Xenium In Situ spatial transcriptomics to eight samples collected from non-small-cell lung cancers (NSCLC) (four after chemoimmunotherapy, four untreated), extracted 90 TLS regions, generated approximately 320,000 single-cell profiles from those regions, and analyzed the endothelial compartment within each TLS. We independently assessed the exploratory findings using multiplex immunofluorescence and survival analysis in a separate cohort of 45 patients receiving immunotherapy. RESULTS: Spatial mapping revealed a reproducible, B-cell-dominant TLS architecture across all samples. Mature TLSs contained CXCL13-rich follicular cores and were associated with a favorable prognosis. Within the endothelial compartment, high endothelial cells (HECs) forming high-endothelial venules (HEVs) segregated from other endothelial cells; in mature TLSs these HECs exhibited high inhibitor of DNA binding 1 (ID1) expression and an adhesion molecular signature, promoting lymphocyte recruitment. Patients with tumors harboring ID1-high HEVs showed higher response rates and pronounced survival advantage; multivariable analysis confirmed ID1-high status as an independent prognostic factor. Conversely, ICB exposure eventually reduced ID1 expression and adhesion molecule levels in HECs, impaired lymphocyte trafficking, and promoted a shift toward a remodeled endothelial state. CONCLUSIONS: ID1expression, linked to HEC differentiation during TLS maturation or ICB exposure, marks a functionally mature, lymphocyte-recruiting HEV that predict durable response to immunotherapy. These findings provide a novel mechanistic framework and practical biomarkers for HEV-centered immuno-oncology strategies in NSCLC.
