Cardiac perforation following transcatheter PFO closure.

From December 1998 to August 2001, transcatheter closure of patent foramen ovale (PFO) with an Amplatzer PFO occluder has been successfully performed in our center in 102 patients without severe complications. We are reporting the first known case of cardiac perforation by an Amplatzer PFO occluder.     

Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin

Bivalirudin is a synthetic antithrombin sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether antilepirudin antibodies recognize epitopes on bivalirudin. Antilepirudin antibody-positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analyzed. Lepirudin- and bivalirudin-coated microtiter plates were used for antibody testing in an enzyme-linked immunosorbent assay (ELISA) system. Of the 43 sera-containing antibodies binding to lepirudin, 22 (51.2%) contained antibodies that also recognized bivalirudin. Binding of these antibodies to bivalirudin was inhibited by more than 70% by preincubation with high doses of bivalirudin. However, if lepirudin-coated microtiter plates were used, high concentrations of bivalirudin inhibited only 2 of the 43 positive sera by more than 30%. Therefore antihirudin antibodies must be polyspecific. The clinical consequences of this cross-reactivity are unknown but bivalirudin, targeted by antibodies of patients treated with lepirudin previously, could potentially boost antibody titers in such patients or even trigger an immune response by itself. Clinically significant antibody formation in response to bivalirudin monotherapy has not been observed, however. Yet, as lepirudin and antilepirudin antibodies have recently been implicated in severe anaphylactic reactions, caution is warranted when using bivalirudin in patients previously treated with lepirudin.     

Peer environment mediates parental history and individual risk in the etiology of cannabis use disorder in boys: a 10-year prospective study

Previous research has shown that a trait termed neurobehavior disinhibition (ND) measured in childhood predicts substance use disorder by young adulthood. The present investigation extends these findings by determining the degree to which peer environment mediates the association between ND and development of cannabis use disorder (CUD). ND was measured in a sample of 216 boys 10-12 years of age. The peer environment was assessed at age 16. Current CUD was determined at age 22. Paternal and maternal SUD predicted son's ND which, in turn, predicted son's peer environment and, subsequently, son's cannabis use frequency and CUD. Peer environment mediated the association between ND and cannabis use and ND and CUD. Maternal and paternal SUD predicted the peer environment. Parental SUD, son's ND, and son's peer environment predicted CUD at age 22 with 84% accuracy.     

Copolymerization of CO2 and epoxides mediated by zinc organyls

Herein we report the copolymerization of CHO with CO₂ in the presence of various zinc compounds R₂Zn (R = Et, Bu, iPr, Cy and Ph). Several zinc organyls proved to be efficient catalysts for this reaction in the absence of water and co-catalyst. Notably, readily available Bu₂Zn reached a TON up to 269 and an initial TOF up to 91 h⁻¹. The effect of various parameters on the reaction outcome has been investigated. Poly(ether)carbonates with molecular weights up to 79.3 kg mol⁻¹ and a CO₂ content of up to 97% were obtained. Under standard reaction conditions (100 °C, 2.0 MPa, 16 h) the influence of commonly employed co-catalysts such as PPNCl and TBAB has been investigated in the presence of Et₂Zn (0.5 mol%). The reaction of other epoxides (e.g. propylene and styrene oxide) under these conditions led to no significant conversion or to the formation of the respective cyclic carbonate as the main product.

Simple zinc organyls (R₂Zn) efficiently catalyze the copolymerization of CO₂ and cyclohexene oxide. The effect of various reaction parameters has been studied. The reaction proceeds under halogen-free conditions and no co-catalyst is required.     

Preoperative anemia and extensive transfusion during stay-in-hospital are critical for patient`s mortality: A retrospective multicenter cohort study of oncological patients undergoing radical cystectomy

Background

Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany.

Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study

Background

Venous thromboembolism (VTE) is a relatively rare condition in childhood with treatment mainly based on extrapolation from studies in adults. Therefore, clinical trials of anticoagulation in children require novel approaches to deal with numerous challenges. The EINSTEIN-Jr program identified pediatric rivaroxaban regimens commencing with in vitro dose finding studies followed by evaluation of children of different ages through phase I and II studies using extensive modeling to determine bodyweight-related doses. Use of this approach resulted in drug exposure similar to that observed in young adults treated with rivaroxaban 20?mg once-daily.

Methods

EINSTEIN-Jr phase III is a randomized, open-label, study comparing the efficacy and safety of rivaroxaban 20?mg-equivalent dose regimens with those of standard anticoagulation for the treatment of any types of acute VTE in children aged 0–18?years.A total of approximately 500 children are expected to be included during the 4-year study window. Flexibility of treatment duration is allowed with study treatment to be given for 3?months with the option to continue treatment in 3-month increments, up to a total of 12?months. However, based on most common current practice, children younger than 2?years with catheter-related thrombosis will have a main treatment period of 1?month with the option to prolong treatment in 1-month increments, up to a total of 3?months.

Conclusions

EINSTEIN-Jr will compare previously established 20?mg-equivalent rivaroxaban dosing regimens with standard anticoagulation for the treatment of VTE in children. Demonstration of similarity of disease, as well as equivalent rivaroxaban exposure and exposure-response will enable extrapolation of efficacy from adult trials, which is critical given the challenges of enrollment in pediatric anticoagulation trials.

Trial registration

Clinicaltrials.gov NCT02234843, registered on 9 September 2014.