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Purpose: To assess the technical feasibility, safety, and clinical success rate of trans-arterial embolization (TAE) as an emergency treatment for acute lower gastrointestinal bleeding (LGIB)., Materials and Methods: Consecutive patients who received urgent TAE due to active LGIB at five academic centers in Germany were retrospectively analyzed. LGIB was confirmed and localized using contrast-enhanced computed tomography (CT) or endoscopy. Outcome parameters including technical and clinical success rates as well as ischemia-related adverse events were analyzed. Furthermore, treatment-related variables that may affect technical and clinical success were analyzed using a regression model., Results: One hundred and forty-one patients were included. TAE was performed in 91% (128/141) of patients. In 81% (114/141) of patients, TAE was performed due to active bleeding visible at angiography, the remaining 10% (14/141) underwent empiric embolization based on pre-interventional imaging. In 9% (13/141) of patients, no TAE was performed. Microcoils were the most used embolic 48.5% (62/128), followed by glue 23.5% (30/128) and Microparticles (8%; 10/128). In the case of bleeding visible in angiography, the technical success rate was 100% (114/114); the clinical success rate was 93.6% (120/128). Severe ischemia-related adverse events necessitating bowel surgery occurred in 14% (18/128) of all patients after embolization. Thirty-day mortality was 14% (21/141). Regression analysis revealed no significant correlations but a statistical trend toward a higher incidence of bowel resection when glue was used (p = 0.090) and toward a higher 30-day mortality when an unselective embolization was performed (p = 0.057)., Conclusion: TAE for LGIB has a high technical and clinical success rate. Severe ischemia-related adverse events necessitating bowel surgery occurred in 14% of patients without identifying a significant correlation to the embolization technique or an embolic., Key Points: Question Is trans-arterial embolization (TAE) viable as an emergency treatment for acute lower gastrointestinal bleeding (LGIB)? Findings TAE demonstrated a 100% technical and 93.6% clinical success rate in treating acute LGIB, with severe ischemia-related adverse events occurring in 14% of patients. Clinical relevance TAE is highly effective and has an acceptable complication rate in treating lower gastrointestinal bleeding, emphasizing the need for a direct head-to-head comparison between endovascular and endoscopic therapy., (© 2024. The Author(s).)

Background: Surgery represents the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC), but recurrence in more than 85% of patients limits the success of curative-intent tumor resection. Neural invasion (NI), particularly the spread of tumor cells along nerves into extratumoral regions of the pancreas, constitutes a well-recognized risk factor for recurrence. Hence, monitoring and therapeutic targeting of NI offer the potential to stratify recurrence risk and improve recurrence-free survival. Based on the evolutionary conserved dual function of axon and vessel guidance molecules, we hypothesize that the proangiogenic vessel guidance factor placental growth factor (PlGF) fosters NI. To test this hypothesis, we correlated PlGF with NI in PDAC patient samples and functionally assessed its role for the interaction of tumor cells with nerves., Methods: Serum levels of PlGF and its soluble receptor sFlt1, and expression of PlGF mRNA transcripts in tumor tissues were determined by ELISA or qPCR in a retrospective discovery and a prospective validation cohort. Free circulating PlGF was calculated from the ratio PlGF/sFlt1. Incidence and extent of NI were quantified based on histomorphometric measurements and separately assessed for intratumoral and extratumoral nerves. PlGF function on reciprocal chemoattraction and directed neurite outgrowth was evaluated in co-cultures of PDAC cells with primary dorsal-root-ganglia neurons or Schwann cells using blocking anti-PlGF antibodies., Results: Elevated circulating levels of free PlGF correlated with NI and shorter overall survival in patients with PDAC qualifying for curative-intent surgery. Furthermore, high tissue PlGF mRNA transcript levels in patients undergoing curative-intent surgery correlated with a higher incidence and greater extent of NI spreading to tumor-distant extratumoral nerves. In turn, more abundant extratumoral NI predicted shorter disease-free and overall survival. Experimentally, PlGF facilitated directional and dynamic changes in neurite outgrowth of primary dorsal-root-ganglia neurons upon exposure to PDAC derived guidance and growth factors and supported mutual chemoattraction of tumor cells with neurons and Schwann cells., Conclusion: Our translational results highlight PlGF as an axon guidance factor, which fosters neurite outgrowth and attracts tumor cells towards nerves. Hence, PlGF represents a promising circulating biomarker of NI and potential therapeutic target to improve the clinical outcome for patients with resectable PDAC., (© 2024. The Author(s).)

Objectives: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19., Methods: Interim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15., Results: Of the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04-3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously., Conclusions: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)