Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia.

Background: Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies.

Methods: In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily.

The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial.

Background: The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor.

Methods: This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial.

Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

Background: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

Methods: Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis.

A randomized trial of budiodarone in paroxysmal atrial fibrillation.

Objective: The aim of this study was to investigate the preliminary safety and efficacy of three doses of budiodarone in patients with paroxysmal atrial fibrillation.

Background: Budiodarone is a chemical analogue of amiodarone and shares its mixed ion channel electrophysiological properties. It has a shorter half-life than amiodarone.

Complexity of inflammatory responses in endothelial cells and vascular smooth muscle cells determined by microarray analysis.

To better understand the molecular basis of vascular cell system behavior in inflammation, we used gene expression microarrays to analyze the expression of 7,075 genes and their response to IL-1beta and TNFalpha in cultures of coronary artery endothelium and smooth muscle derived from a single coronary artery. The most noticeable difference between the cell types was the considerably greater magnitude and complexity of the transcriptional response in the endothelial cells. Two hundred and nine genes were regulated in the endothelium and only 39 in vascular smooth muscle.

Experimental studies on the protective efficacy of a Pseudomonas aeruginosa vaccine.

Pseudomonas aeruginosa vaccine (PV) containing cell proteins with molecular weight (Mr) 20,000-100,000 and up to 0.08% (w/v) admixture of lipopolysaccharide was obtained by water-salt extraction and subsequent ultrafiltration. PV protects mice against experimental P.

[Experimental vaccinal prophylaxis of Pseudomonas aeruginosa burn sepsis].

After the injection of P. aeruginosa live culture under the burned skin of mice sepsis develops within the first 24 hours, finally leading to the death of the animals. The microorganisms can be isolated from the blood, liver, kidneys and mesenterial lymph nodes till day 3 and from the spleen till day 5.

[Characteristics of Pseudomonas aeruginosa pili and an elucidation of their relation to the virulence of the bacteria].

The electron microscopic study of 175 P. aeruginosa museum and newly isolated strains has been made and their virulence has been determined. In 32% of these strains the presence of pili has been established.

[Cell-free Pseudomonas vaccine: its immunochemical characteristics and immunogenicity].

Two variants of cell-free protein vaccine have been prepared from the mixture of 4 P. aeruginosa strains, serovars 02, 06, 07 and 011, and from a single P. aeruginosa strain, serovar 02.