Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study.

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC).

Fibrinolysis biomarker, thrombin, and activated protein C level alterations after coagulation activation depend on type of thrombophilia and clinical phenotype.

Background: Recently, we have shown alterations in the anticoagulant response to recombinant activated factor VII (rFVIIa)-induced coagulation activation in patients with thrombophilia.

Objectives: This study aimed to extend this model to fibrinolysis biomarkers.

Methods: This interventional study included 56 patients with thrombophilia and previous venous thromboembolism (VTE+), 38 without VTE (VTE-), and 35 healthy controls.

Hemostatic imbalance induced by tamoxifen in estrogen receptor-positive breast cancer patients: An observational study.

Background: Estrogen receptor (ER)-positive (ER+) breast cancer accounts for approximately 75% of all breast cancers. Tamoxifen, a selective estrogen receptor modulator, is the standard adjuvant treatment. Although better tolerated than aromatase inhibitors, tamoxifen increases the risk of venous thromboembolism (VTE) 1.

The impact of Bis-GMA free and Bis-GMA containing resin composite as posterior restoration on marginal integrity: a randomized controlled clinical trial.

Background: There have been concerns surrounding the utilization of Bis-GMA, a type of bisphenol A (BPA) derivative, within the dental industry. The aim of this study was to compare the performance of bulk fill Bis-GMA-free resin composite class II restorations in respect of its marginal integrity in comparison to bulk fill Bis-GMA-containing resin composite class II restorations over a 12-month period in a parallel clinical trial utilizing a split-mouth, double-blind, randomized strategy.

Methods: 20 patients participated in this study.

Juvenile Recurrent Parotitis: Video-Documented Sialendoscopy.

Juvenile recurrent parotitis (JRP) is characterised by recurrent episodes of painful parotid swelling in children. JRP is the second most common cause of parotitis in childhood, behind only paramyxovirus. The prevention of recurrent attacks represents the most dramatic and serious aspect of this pathology.

Inactive Matrix Gla Protein in Relation to Renal and Cardiac Functions and Cardiac Valvular Calcification Among Type 2 Diabetes Patients.

Background: Matrix Gla protein (MGP) is a robust innate suppressor of the detrimental process of vascular calcification in the human body.

Objectives: The interrelationship between circulating MGP levels and renal and cardiac dysfunction, besides echocardiographic calcification score (ECS) was investigated in a sample of type 2 diabetes (T2D) patients.

Methods: The study included 130 subjects.

Ex Vivo Modeling of the PC (Protein C) Pathway Using Endothelial Cells and Plasma: A Personalized Approach.

Background: The endothelial cell-dependent PC (protein C) pathway is critically involved in the regulation of coagulation, anti-inflammatory, and cytoprotective signaling. Its reactivity shows high interindividual variability, and it contributes to prothrombotic disorders, such as the FVL (factor V Leiden) mutation.

Methods: Endothelial colony-forming cells (ECFCs) were isolated from heparinized peripheral blood from healthy individuals and FVL carriers.

Variation in Plasma Levels of Apixaban and Rivaroxaban in Clinical Routine Treatment of Venous Thromboembolism.

Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are broadly used in the management of venous thromboembolism (VTE). Although not routinely required, measurement of their plasma concentration is advised for an increasing number of indications. Due to the lack of therapeutic ranges, current guidelines recommend reporting DOAC plasma levels together with expected levels from previous pivotal studies.

Increased Prevalence of Elevated D-Dimer Levels in Patients on Direct Oral Anticoagulants: Results of a Large Retrospective Study.

Elevated D-dimer levels during anticoagulant therapy with vitamin K antagonists (VKA) are associated with an increased risk of thrombosis. It has been hypothesized that elevated D-dimer levels in patients receiving direct oral anticoagulants (DOACs) also indicate an increased risk of thrombosis recurrence, but data on the distribution of D-dimer levels in patients with VTE on DOACs are sparse. In the present study we retrospectively analyzed D-dimer levels in patients taking DOACs after first or recurrent venous thrombosis ( = 1,716, 1,126 thereof rivaroxaban, 481 apixaban, 62 edoxaban, and 47 dabigatran).

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices.

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.

PC Deficiency Testing: Thrombin-Thrombomodulin as PC Activator and Aptamer-Based Enzyme Capturing Increase Diagnostic Accuracy.

Protein C (PC) activity tests are routinely performed in a thrombophilia workup to screen for PC deficiency. Currently used tests combine conversion of PC to activated PC (APC) by the snake venom Protac with subsequent APC detection through hydrolysis of a chromogenic peptide substrate or prolongation of a clotting time. In this prospective cohort study, we analyzed how different modes of PC activation and subsequent APC determination influence the diagnostic accuracy of PC activity testing in a cohort of 31 patients with genetically confirmed PC deficiency.

Prognostic and Therapeutic Implications of Immune Classification by CD8 Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30-50%. As immunotherapy may be a new therapeutic option, we analyzed CD8 tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8 TILs and PD-L1) in a series of 57 SNSCCs.

Functional Characterization of Antithrombin Mutations by Monitoring of Thrombin Inhibition Kinetics.

Inactivation of thrombin by the endogenous inhibitor antithrombin (AT) is a central mechanism in the regulation of hemostasis. This makes hereditary AT deficiency, which is caused by SERPINC1 gene mutations, a major thrombophilic risk factor. Aim of this study was to assess to what extent AT mutations impair thrombin inhibition kinetics.

Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?

Hemostasis is a complex process in which abnormalities can cause shifts toward prothrombotic or prohemorrhagic states resulting in thrombosis or bleeding, respectively. Several coagulation tests may be required to characterize these defects but may yet not always reflect a patient's true hemostatic capacity. Thus, global coagulation tests aiming to simulate the coagulation process in vitro instead of measuring single components thereof are certainly of interest to assess prothrombotic or prohemorrhagic tendencies.

Functional lupus anticoagulant testing in a large retrospective cohort of thrombosis patients with direct oral anticoagulants.

Functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. There is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DOACs). In this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVT), LA-sensitive aPTT, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs).

CD8 Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma.

Background: Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35-80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options.

Increased Activated Protein C Response Rates Reduce the Thrombotic Risk of Factor V Leiden Carriers But Not of Prothrombin 20210G>A Carriers.

Rationale: Carriers of the most common prothrombotic mutations FVL (factor V Leiden) and FII (prothrombin) 20210G>A show a highly variable clinical phenotype. Using standardized in vivo coagulation activation followed by activity pattern analysis we have recently shown, that the FVL mutation accelerates thrombin and APC (activated protein C) formation in carriers without a history of venous thromboembolism (VTE).

Objective: The aim of this prospective cohort study was to investigate, if the FII 20210G>A mutation induces a similar reaction pattern, and if the response rates differ in FVL and FII 20210G>A mutation carriers with prior VTE (VTE+).

Activated Factor X-Based versus Thrombin-Based Antithrombin Testing in Thrombophilia Workup in the DOAC Era.

Antithrombin (AT) activity tests are used for diagnosing hereditary AT deficiency, a main genetic determinant of thrombophilia. They are either based on inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have been suggested to be preferable to FIIa-based assays due to their higher sensitivity for certain AT deficiency causing mutations.

Programmed death ligand-1 expression as immunotherapeutic target in sinonasal cancer.

Background: Sinonasal cancer carries a poor prognosis, especially in recurrent stages, and it is a disease with very limited treatment options.

Methods: The expression of programmed death ligand-1 (PD-L1) as a marker for immunotherapy was evaluated in 53 sinonasal squamous cell carcinoma (SCC) and 126 intestinal-type adenocarcinoma (ITAC) samples. Results were correlated to clinicopathological characteristics and follow-up data.

Through modulation of cardiac Ca handling, UCP2 affects cardiac electrophysiology and influences the susceptibility for Ca -mediated arrhythmias.

What is the central question of this study? Knockdown of UCP2 reduces mitochondrial Ca uptake. This suggests that Ucp2 knockout mice need to have additional effects on cytosolic Ca handling to prevent Ca overload. However, the specific mechanisms and their impact on cardiac electrophysiology remain speculative.

Characteristics of coronary artery disease among patients with atrial fibrillation compared to patients with sinus rhythm.

Background: With a high prevalence of coronary artery disease (CAD) among patients with atrial fibrillation (AF), CAD is one of the main risk factors for AF. However, little is known about the characteristics of CAD in AF patients, especially whether a specific anatomical distribution of coronary artery stenoses might predispose an individual to AF via atrial ischemia remains speculative. To address this issue, we evaluated the potential associations between angiographic characteristics of CAD and AF.

UCP3 Regulates Single-Channel Activity of the Cardiac mCa1.

Mitochondrial Ca(2+) uptake (mCa(2+) uptake) is thought to be mediated by the mitochondrial Ca(2+) uniporter (MCU). UCP2 and UCP3 belong to a superfamily of mitochondrial ion transporters. Both proteins are expressed in the inner mitochondrial membrane of the heart.