Factor XIII: Driving (Cross-)Links in Hemostasis, Thrombosis, and Disease.

Blood clots are complex structures composed of blood cells and proteins held together by the structural framework provided by an insoluble fibrin network. Factor (F)XIII is a protransglutaminase essential for stabilizing the fibrin network. Activated FXIII(a) introduces novel covalent crosslinks within and between fibrin and other plasma and cellular proteins, and thereby promotes fibrin biochemical and mechanical integrity.

Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.

Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).

Continuous vital sign monitoring of patients recovering from surgery on general wards: a narrative review.

Most postoperative deaths occur on general wards, often linked to complications associated with untreated changes in vital signs. Monitoring in these units is typically intermittent checks each shift or maximally every 4-6 h, which misses prolonged periods of subtle changes in physiology that can herald a critical downstream event. Continuous monitoring of vital signs is therefore intuitively necessary for patient safety.

Association of intraoperative hypotension and cumulative norepinephrine dose with postoperative acute kidney injury in patients having noncardiac surgery: a retrospective cohort analysis.

Background: Intraoperative hypotension is associated with acute kidney injury (AKI). Clinicians thus frequently use vasopressors, such as norepinephrine, to maintain blood pressure. However, vasopressors themselves might promote AKI.

Electrical cardiometry for non-invasive cardiac output monitoring: a method comparison study in patients after coronary artery bypass graft surgery.

Cardiac output can be estimated non-invasively by electrical cardiometry with the ICON® monitor (Osypka Medical GmbH, Berlin, Germany). Conflicting results have been reported regarding the cardiac output measurement performance of electrical cardiometry. In this prospective method comparison study, we compared cardiac output measured using electrical cardiometry (EC-CO; test method) with cardiac output measured using intermittent pulmonary artery thermodilution (PATD-CO; reference method) in patients after coronary artery bypass graft (CABG) surgery.

Personalized perioperative blood pressure management in patients having major non-cardiac surgery: A bicentric pilot randomized trial.

Study Objective: We hypothesize that personalized perioperative blood pressure management maintaining intraoperative mean arterial pressure (MAP) above the preoperative mean nighttime MAP reduces perfusion-related organ injury compared to maintaining intraoperative MAP above 65 mmHg in patients having major non-cardiac surgery. Before testing this hypothesis in a large-scale trial, we performed this bicentric pilot trial to determine a) if performing preoperative automated nighttime blood pressure monitoring to calculate personalized intraoperative MAP targets is feasible; b) in what proportion of patients the preoperative mean nighttime MAP clinically meaningfully differs from a MAP of 65 mmHg; and c) if maintaining intraoperative MAP above the preoperative mean nighttime MAP is feasible in patients having major non-cardiac surgery.

Design: Bicentric pilot randomized trial.

Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.

Impaired secretion of an essential blood coagulation factor fibrinogen leads to hepatic fibrinogen storage disease (HFSD), characterized by the presence of fibrinogen-positive inclusion bodies and hypofibrinogenemia. However, the molecular mechanisms underlying the biogenesis of fibrinogen in the endoplasmic reticulum (ER) remain unexplored. Here we uncover a key role of SEL1L-HRD1 complex of ER-associated degradation (ERAD) in the formation of aberrant inclusion bodies, and the biogenesis of nascent fibrinogen protein complex in hepatocytes.

Wire-in-needle versus conventional syringe-on-needle technique for ultrasound-guided central venous catheter insertion in the internal jugular vein: the WIN randomized trial.

Purpose: There are different techniques for ultrasound-guided central venous catheter (CVC) insertion. When using the conventional syringe-on-needle technique, the syringe needs to be removed from the needle after venous puncture to pass the guidewire through the needle into the vein. When, alternatively, using the wire-in-needle technique, the needle is preloaded with the guidewire, and the guidewire-after venous puncture-is advanced into the vein under real-time ultrasound guidance.

Suppressing upregulation of fibrinogen after polytrauma mitigates thrombosis in mice.

Background: Polytrauma results in systemic inflammation and increased circulating fibrinogen, which increases the risk of microvascular and macrovascular thrombosis that contributes to secondary organ damage and venous thromboembolism (VTE). There are no clinically approved agents to prevent hyperfibrinogenemia after polytrauma. We hypothesized that preventing the increase in fibrinogen levels after polytrauma would suppress thrombosis.

Assisted Fluid Management and Sublingual Microvascular Flow During High-Risk Abdominal Surgery: A Randomized Controlled Trial.

Background: Implementation of goal-directed fluid therapy (GDFT) protocols remains low. Protocol compliance among anesthesiologists tends to be suboptimal owing to the high workload and the attention required for implementation. The assisted fluid management (AFM) system is a novel decision support tool designed to help clinicians apply GDFT protocols.

The impact of a digital guideline version on schizophrenia guideline knowledge: results from a multicenter cluster-randomized controlled trial.

Background: Clinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals.

The catheterized bladder environment induces dysregulation of macrophage polarization exacerbating bacterial UTI.

Urinary catheterization causes bladder damage, predisposing hosts to catheter-associated urinary tract infections (CAUTIs). CAUTI pathogenesis is mediated by bladder damage-induced inflammation, resulting in accumulation and deposition of the blood-clotting protein fibrinogen (Fg) and its matrix form fibrin, which are exploited by uropathogens as biofilm platforms to establish infection. Catheter-induced inflammation also results in robust immune cell recruitment, including macrophages (Mϕs).

Personalised blood pressure management during major noncardiac surgery and postoperative neurocognitive disorders: a randomised trial.

Background: It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised-compared to routine-intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery.

Methods: In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.

[Intraoperative clinical application of hemodynamic monitoring in noncardiac surgery patients].

The current S1 guidelines on the intraoperative clinical application of hemodynamic monitoring in patients scheduled for noncardiac surgery are presented based on a case report under the aspect of an optimized intraoperative anesthesiological management. The S1 guidelines were developed with the aim of identifying the questions on the intraoperative hemodynamic monitoring and management which are important for the routine daily clinical practice, to discuss them in a guideline group and to answer them based on the current state of scientific knowledge. The guidelines were written under the auspices of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and published by the AWMF in 2023 under the register number 001/049.

Fighting fibrin with fibrin: Vancomycin delivery into coagulase-mediated Staphylococcus aureus biofilms via fibrin-based nanoparticle binding.

Staphylococcus aureus skin and soft tissue infection is a common ailment placing a large burden upon global healthcare infrastructure. These bacteria are growing increasingly recalcitrant to frontline antimicrobial therapeutics like vancomycin due to the prevalence of variant populations such as methicillin-resistant and vancomycin-resistant strains, and there is currently a dearth of novel antibiotics in production. Additionally, S.

4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mouse hemostasis model.

Interplay between platelets, coagulation factors, endothelial cells (ECs), and fibrinolytic factors is necessary for effective hemostatic plug formation. This study describes a 4-dimensional (4D) imaging platform to visualize and quantify hemostatic plug components in mice with high spatiotemporal resolution. Fibrin accumulation after laser-induced vascular injury was observed at the platelet plug-EC interface, controlled by the antagonistic balance between fibrin generation and breakdown.

Post-anesthesia care unit hypotension in low-risk patients recovering from non-cardiac surgery: a prospective observational study.

Intraoperative hypotension is common and associated with organ injury. Hypotension can not only occur during surgery, but also thereafter. After surgery, most patients are treated in post-anesthesia care units (PACU).

Coagulation and platelet biology at the intersection of health and disease: illustrated capsules of the 11th Symposium on Hemostasis at the University of North Carolina.

The University of North Carolina Symposia on Hemostasis began in 2002, with The First Symposium on Hemostasis with a Special Focus on FVIIa and Tissue Factor. They have occurred biannually since and have maintained the primary goal of establishing a forum for the sharing of outstanding advances made in the basic sciences of hemostasis. The 2024 11th Symposium on Hemostasis will bring together leading scientists from around the globe to present and discuss the latest research related to coagulation factors and platelet biology.

Processed electroencephalography-guided general anesthesia and norepinephrine requirements: A randomized trial in patients having vascular surgery.

Study Objective: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery.

Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections.

Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A.

Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity.

Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery: Guidelines of the German Society of Anaesthesiology and Intensive Care Medicine in collaboration with the German Association of the Scientific Medical Societies.

Haemodynamic monitoring and management are cornerstones of perioperative care. The goal of haemodynamic management is to maintain organ function by ensuring adequate perfusion pressure, blood flow, and oxygen delivery. We here present guidelines on "Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery" that were prepared by 18 experts on behalf of the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin; DGAI).