Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.     

Fibrous hamartoma of infancy. A study of eight cases with immunohistochemical and electron microscopical findings.

Eight cases of fibrous hamartomas of infancy are presented. Actin positivity and desmin negativity in collagen forming spindle-shaped cells and electron microscopical findings point to the myofibroblastic nature of this entity. "Dark cells" which spread regularly in all but one of our tumors were immunohistochemically determined to be a mixture of B and T cell lymphocytes. Their selective location and possible role are discussed.     

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.     

In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia

In chronic myelomonocytic leukemia (CMML), colony‐forming units granulocyte/macrophage (CFU‐GM), which grow in vitro in the absence of exogenous growth factors, arise from the abnormal clone that is responsible for the overproduction of granulomonocytic cells. Previous in vitro findings including ours suggest that divergent molecular aberrations in CMML seem to converge within the GM‐CSF signaling pathway. As JAK2 is a sentinel kinase in this pathway, JAK2 inhibition may be an attractive treatment approach in CMML. We investigated the in vitro effects of the specific JAK2 inhibitor TG101209 on the autonomous CFU‐GM formation from peripheral blood mononuclear cells of patients with CMML. TG101209 was found to either block or strongly inhibit spontaneous CFU‐GM growth in all 10 patients tested. This inhibitory effect was dose dependent and significantly more pronounced as compared to the inhibitory effect on stimulated CFU‐GM growth from normal individuals. In a CMML patient with splenomegaly, who was treated with the JAK1/2 inhibitor ruxolitinib off label, we can demonstrate a spleen response and the disappearance of constitutional symptoms which was associated with a decrease in autonomous CFU‐GM formation ex vivo. Pharmacological JAK2 inhibition may be an interesting approach to be systematically studied in patients with CMML.     

Is prevention of atopic eczema with hydrolyzed formulas cost-effective? A health economic evaluation from Germany

To cite this article: Mertens J, Stock S, Lüngen M, Berg AV, Kr?mer U, Filipiak-Pittroff B, Heinrich J, Koletzko S, Grübl A, Wichmann H-E, Bauer C-P, Reinhardt D, Berdel D, Gerber A. Is Prevention of Atopic Eczema with Hydrolyzed Formulas Cost-Effective? A Health Economic Evaluation from Germany. Pediatr Allergy Immunol 2012: 23: 597-604. ABSTRACT: Objective: The German Infant Nutritional Intervention (GINI) trial, a prospective, randomized, double-blind intervention, enrolled children with a hereditary risk for atopy. When fed with certain hydrolyzed formulas for the first 4?months of life, the risk was reduced by 26-45% in PP and 8-29% in intention-to-treat (ITT) analyses compared with children fed with regular cow's milk at age 6. The objective was to assess the cost-effectiveness of feeding hydrolyzed formulas. Patients and Methods: Cost-effectiveness was assessed with a decision tree model programmed in TreeAge. Costs and effects over a 6-yr period were analyzed from the perspective of the German statutory health insurance (SHI) and a societal perspective at a 3% effective discount rate followed by sensitivity analyses. Results: The extensively hydrolyzed casein formula would be the most cost-saving strategy with savings of 478?€ per child treated in the ITT analysis (CI95%: 12?€; 852?€) and 979?€ in the PP analysis (95%CI: 355?€; 1455?€) from a societal perspective. If prevented cases are considered, the partially whey hydrolyzed formula is cost-saving (ITT -5404?€, PP -6358?€). From an SHI perspective, the partially whey hydrolyzed formula is cost-effective, but may also be cost-saving depending on the scenario. An extensively hydrolyzed whey formula also included into the analysis was dominated in all analyses. Conclusions: For the prevention of AE, two formulas can be cost-effective or even cost-saving. We recommend that SHI should reimburse formula feeding or at least the difference between costs for cow's milk formula and the most cost-effective formula.