Colistin Reduces LPS-Triggered Inflammation in a Human Sepsis Model In Vivo: A Randomized Controlled Trial.

The previously described anti-endotoxin effect of colistin has not been investigated in humans yet. We performed a randomized, double-blind, placebo-controlled crossover trial to determine the degree of colistin-driven modulation of inflammatory response in blood of lipopolysaccharide (LPS)-challenged healthy volunteers in a human endotoxemia model. After a single intravenous dose of 2.5 million IU colistin methanesulfonate, interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), and IL-1ß concentrations as well as other biomarkers of inflammation such as C-reactive protein, differential leukocyte counts, and body temperature were measured up to 24 h postdose. Colistin significantly decreased the inflammatory cytokine response to LPS in blood of healthy volunteers. This effect was most evident for IL-6, IL-8, and TNF-α. This study is the first to confirm the anti-endotoxin effect of colistin in humans in vivo. Further studies might increase our knowledge on the interaction between colistin and the effectors of the immune system.

Alemtuzumab-BEAM as conditioning for allogeneic hematopoietic stem cell transplantation in relapsed/refractory Hodgkin lymphoma: a single-center analysis.

PURPOSE: Treatment of refractory Hodgkin disease deserves specific considerations. Recently, alemtuzumab-BEAM has been introduced in allogeneic hematopoietic stem cell transplantation (HSCT) in these patients. METHODS: We retrospectively analyzed the outcome of 20 patients with relapsed/refractory Hodgkin's lymphoma (HL) who received allogeneic HSCT following conditioning therapy with alemtuzumab-BEAM. RESULTS: Treatment-related toxicity was tolerable. Half of the patients (50 %) had infections. Of these, 50 % were found to have pneumonia or catheter-related infections. In 20 %, an oral mucositis was observed. Acute graft-versus-host disease (GvHD) (≥grade 2) was seen in three patients. Complete remission (CR) could be achieved in 17 patients (85 %), 2 patients had persistent Hodgkin disease, and 1 patient died from infection prior to CR evaluation. Median progression-free survival and overall survival were 17.9 and 67.5 months, respectively. From the 17 CR patients, 8 had a relapse after a median of 10 months. Notably, of the eight patients relapsing after HSCT, all patients received another salvage treatment and four patients are still alive, whereas the other four patients died due to further progress. Six out of the remaining nine patients are still in CR, whereas the other three died from chronic GvHD and multi-organ failure. Overall, seven patients experienced chronic GvHD. CONCLUSION: In summary, alemtuzumab-BEAM is a well-tolerated conditioning therapy for allogeneic HSCT with high response rates in refractory HL.

Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects.

UNLABELLED: ESSENTIALS: It is unknown whether single rivaroxaban doses should best be administered in the morning or evening. Circadian rhythm of coagulation/fibrinolysis was measured after morning or evening intake of rivaroxaban. Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations. Evening intake of rivaroxaban better matches the morning hypofibrinolysis. BACKGROUND: A circadian variation of the endogenous coagulation system exists with hypercoagulability and hypofibrinolysis and a corresponding peak of cardiovascular thromboembolic events in the morning. So far, no information is given as to whether single daily doses of the new oral anticoagulant drug rivaroxaban should best be administered in the morning or the evening. MATERIALS AND METHODS: Sixteen healthy male or female volunteers with a mean age of 26 ± 7 years were included in this randomized, controlled, analyst-blinded cross-over clinical trial. All subjects were given three morning and three evening single doses of 10 mg rivaroxaban. Circadian rhythms of prothrombin fragment 1 + 2, plasminogen activator inhibitor, and plasmin-antiplasmin complex were measured before any medication intake, as well as after morning or evening medication intake. Rivaroxaban concentrations were determined by an anti-activated factor X assay and liquid chromatography-mass spectrometry. MAIN RESULTS: Concentrations of rivaroxaban were higher 12 h after evening intake of rivaroxaban than 12 h after morning intake (53.3 ng mL(-1) [95% confidence interval 46.0-67.8] vs. 23.3 ng mL(-1) [19.4-29.1, respectively]). Rivaroxaban intake in the evening reduced morning F1+2 concentrations better at 8:00 AM than did administration on awakening (85 ± 25 nmol L(-1) vs. 106 ± 34 nmol L(-1) , CI: 9.4-32.1). In addition, this suppression effect was longer lasting after evening intake. CONCLUSIONS: Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations and better matches the morning hypofibrinolysis. These results might help to further improve the efficacy and safety of rivaroxaban treatment.