Prospective Evaluation of the Pre-, Intra-, and Postoperative Kinetics of ADAMTS-13, von Willebrand Factor, and Interleukin-6 in Vascular Surgery.

Postoperative thrombotic thrombocytopenic purpura (TTP) shows clinical presentation similar to classical TTP, whereas exact pathophysiological contexts remain unexplained. In this study, we investigated intraoperative and postoperative changes in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13), von Willebrand factor (VWF), large VWF multimers, and interleukin-6 (IL-6) in vascular surgery patients. The objective was to compare the impact of endovascular, peripheral, and aortic surgery on target parameters which are supposed to play a role in surgery-associated TTP. A total of 93 vascular surgery patients were included and divided into 4 groups according to the specific type of intervention they underwent. Blood samples were taken preoperatively, intraoperatively, and postoperatively on days 2 and 4. The ADAMTS-13 activity decreased significantly in 3 of the 4 groups during surgery (from median 81% to 49%, P < .001, in the group undergoing aortoiliacal interventions), whereas the percentage of large VWF multimers increased in all groups of patients. von Willebrand factor antigen increased significantly in all groups on postoperative day 2 and IL-6 increased significantly in the intraoperative and early postoperative period. There was no significant correlation between the intraoperative decrease in ADAMTS-13 and the increase in VWF or IL-6. No patient in this study showed clinical picture of TTP; the precise cause and clinical significance of moderately reduced ADAMTS-13 activity in the perioperative setting have not yet been definitely determined.

Impact of pantoprazole on absorption and disposition of hydroxychloroquine, a drug used in Corona Virus Disease-19 (Covid-19): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes). TRIAL DESIGN: Single centre, open-label, parallel group, two-arm, phase I drug-drug interaction trial. PARTICIPANTS: Healthy volunteers (18-60 years old) are treated in the Clinical Pharmacological Trial Center of Heidelberg University Hospital, Germany. INTERVENTION AND COMPARATOR: • Participants are randomized in a group to either receive a nine-day course of pantoprazole, or to a control group without pantoprazole. All participants receive a single dose of HCQ 400 mg. • Additionally, CYP3A4 and CYP2D6 phenotyping with microdosed probe drugs is performed using midazolam and yohimbine as enzyme activity markers, respectively. MAIN OUTCOMES: Primary endpoint: Area under the curve (AUC)0-72 h and maximum concentration (Cmax) of a single oral dose of 400 mg HCQ with and without pantoprazole (changes in these two values describe relevant aspects of exposure to HCQ with and without administration of pantoprazole). Secondary endpoints: • AUC2-4 h, AUC0-6 h and Cmax of midazolam and yohimbine. • Correlation of HCQ concentrations in whole blood with concentrations in plasma and peripheral blood mononuclear cells (PBMC). RANDOMISATION: Participants are assigned to treatment groups by using a randomisation list (1:1, block size = 4) and consecutive enrolment. BLINDING (MASKING): The trial is an open-label trial, participants and investigators are not blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 24 participants (12 per group) are planned to be randomised. TRIAL STATUS: Protocol version 2.1 dated 24/04/2020, first patient first visit. April 30th, 2020, recruitment ongoing, anticipated end of study June 30th, 2020. TRIAL REGISTRATION: EudraCT Number: 2020-001470-30 , registered on 31 March 2020 German Clinical trials register number / International Clinical Trials Registry Platform: DRKS00021573, registered on 27 April 2020 FULL PROTOCOL: The full trial protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full trial protocol. The trial protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).