Background Major ABO mismatch in allogeneic bone marrow transplant (BMT) can cause clinical problems like severe transfusion reactions, acute haemolysis, and delay of red blood cell (RBC) engraftment or manifestation of pure red cell aplasia, related to circulating isoagglutinin titers. Even there is no increased incidence of graft failure or slower engraftment of neutrophils and platelets ABO mismatch leads to an increase of transplant related mortality. To reduce circulating isoagglutinin titers pre transplant plasma exchange during conditioning period can be performed. This procedure can be wearing for the patient and rebound effects are observed. RBC depletion can cause a loss of CD34+stem cells in bone marrow. A further strategy to reduce circulating isoagglutinin titers is in vivo immunoadsorption due to donor type RBC transfusion pre transplant. Aim of the study The Aim of the retrospective single center study was to investigate the safety and tolerability of donor-type red blood cell transfusion prior to allogeneic stem cell transplantation in children with major ABO mismatch. Methods From 2007-2015 37 children (median age 7 years, range 0.6-18.4) received an ABO mismatched RBC transfusion (2-3 ml KG BW) pre transplant under antihistaminic and steroid cover. Reaction to donor type RBC and graft transfusion, number of donor type RBC transfusions, haemolysis parameters, and trend of isoagglutinin titers, and engraftment data were observed. Wilcoxon signed-rank test was used to examine the difference between the paired values of titers (Conventional test tube, CTT; titration method using nonspecific anti-IgG antibody; Anti-IgG gel titer) before and after donor type RBC transfusion. Age and time until engraftment were reported using median and ranges. The quantitative values were reported using frequency and percentage. All statistical tests were two-sided with a significance level of 5%. Data analysis was performed using commercial software R.Statistical methods. Results Safety of mismatched RBC transfusions Compared with accidentally transfused RBC no severe complications are observed in our cohort. 34 (92%) children presented no reactions (Grade 0), 1 child had a minimal oxygen demand,1 child showed a mild hypertension (Grade 1) and 1 child a moderate hypertension, requiring treatment. Neither severe reactions nor anaphylactic shock were observed. Efficiency of mismatched RBC transfusion A significant reduction of isoagglutinin titers was defined as a final titer of 1:4 or at least a reduction of 3 titer steps was achieved. 23 of 37 (64%) required 1 donor type RBC transfusion to reduce significant the isoagglutinin titers, 8 patients (22%) needed a second and 5 patients (14%) a third transfusion. Figure 1 showed the significant reduction of isoagglutinin titers in the different patients groups after donor type RBC transfusion. The pairwise analysis of isoagglutinin titers indicates that the initial titer of patients required one donor type transfusion of RBC was significant lower than in the patient group required 2 or 3 transfusions. Engraftment data The median time to WBC and platelet engraftment was 21.5 (range 19-24) and 28 (range 26-60) days respectively. Haemolysis parameter post mismatched RBC transfusion Haemolysis parameter lactat dehydrogenase (LDH) and bilirubin was determined on a daily base. In all patients no significant increase of bilirubin levels was observed. Conclusion Donor type RBC transfusion is a safe, tolerable and effective procedure to reduce the isoagglutinin titers prior to allogeneic ABO mismatched bone marrow transplantation in children. In our cohort no severe transfusion reactions, acute haemolysis, delay of engraftment or manifestation of pure red cell aplasia was observed. Figure Figure. Disclosures Jarisch: Novartis: Consultancy. Bader:Novartis: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Medac: Research Funding; Riemser: Research Funding; Neovii: Research Funding.

ObjectiveMucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.DesignA randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.ResultsA comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.ConclusionOur study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.Trial RegistrationClinicalTrials.gov NCT02515799

This multicentre study compares the therapeutic efficacy and safety of minaprine (200 mg) to that of imipramine (50, 75, 100 mg) in the treatment of patients over 40 years suffering from dysthymic disorders as diagnosed according to DSM III. After 4–7 days on placebo, 67 patients were randomly assigned to receive either drug for a period of 6 weeks in a double-blind manner. As rated by the Hamilton Depression Rating Scale and evaluated by exploratory statistics, minaprine showed similar efficacy to imipramine in these patients. Minaprine was better tolerated than imipramine according to the physicians’ tolerance rating (p < 0.05) and produced significantly fewer symptoms of the autonomic nervous system as compared to imipramine (p < 0.01).

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