Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma.

INTRODUCTION: Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. METHOD: This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. RESULTS: Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. CONCLUSION: Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody-mediated disease.

AIMS: Both rituximab and plasmapheresis can be associated in the treatment of immune-mediated kidney diseases. The real impact of plasmapheresis on rituximab pharmacokinetics is unknown. The aim of this study was to compare rituximab pharmacokinetics between patients requiring plasmapheresis and others without plasmapheresis. METHODS: The study included 20 patients receiving one or several infusions of rituximab. In 10 patients, plasmapheresis sessions were also performed (between two and six sessions per patient). Rituximab concentrations were measured in blood samples in all patients and in discarded plasma obtained by plasmapheresis using an enzyme-linked immunosorbent assay method. Data were analysed according to a population pharmacokinetic approach. RESULTS: The mean percentage of rituximab removed during the first plasmapheresis session ranged between 47 and 54% when plasmapheresis was performed between 24 and 72 h after rituximab infusion. Rituximab pharmacokinetics was adequately described by a two-compartment model with first-order elimination. Plasmapheresis had a significant impact on rituximab pharmacokinetics, with an increase of rituximab clearance by a factor of 261 (95% confidence interval 146-376), i.e. from 6.64 to 1733 ml h(-1) . Plasmapheresis performed 24 h after rituximab infusion decreased the rituximab area under the curve by 26%. CONCLUSIONS: Plasmapheresis removed an important amount of rituximab when performed less than 3 days after infusion. The removal of rituximab led to a significant decrease of the area under the curve. This pharmacokinetic observation should be taken into account for rituximab dosing, e.g. an additional third rituximab infusion may be recommended when three plasmapheresis sessions are performed after the first rituximab infusion.

Lipid peroxidation in all-in-one admixtures for preterm neonates: impact of amount of lipid, type of lipid emulsion and delivery condition.

AIM: To evaluate the effect of lipid emulsion composition and delivery condition on lipid peroxidation in typical all-in-one parenteral admixtures for preterm neonates. METHODS: Malonedialdehyde (MDA) concentrations were assessed in different all-in-one admixtures. We evaluated the effects of fat blend (three lipid emulsions) and the amount of lipids, as well as the effects of protecting bags and/or tubing from ambient light and storage for 72 h. MDA was measured by liquid chromatography/mass spectrometry. RESULTS: Three hundred and sixty samples were collected from 114 admixtures. Neither the type of lipid (p = 0.43) nor the interaction between light and type of lipid (p = 0.49) had any influence on final MDA concentrations, but the increase in MDA concentration at 24 h (T(24)) was related to light exposure (p < 0.001). The increase in MDA concentration was related to the increase in lipid amount in the admixture at T(0) (r = 0.77) and T(24) (r = 0.86). MDA concentrations in solutions stored for 72 h showed no significant increase, with no difference between the three lipid emulsions (p = 0.69). CONCLUSION: All-in-one admixtures may be interesting for the parenteral nutrition of preterm neonates. Protection from light and restricting the amount of lipid to what is required for appropriate energy provision are essential to limit lipid peroxidation.

Assessment of efficacy of postinfusion tubing flushing in reducing risk of cytotoxic contamination.

PURPOSE: Infusion of cytotoxic drugs carries the risk of occupational exposure of healthcare workers. Since disconnecting an infusion line is a source of contamination, flushing of tubing after infusion of cytotoxic agents is recommended, but the optimal volume of rinsing solution is unknown. The objective of this study was to assess whether postinfusion line flushing completely eliminates cytotoxics. METHODS: Infusions were simulated with 3 cytotoxics (gemcitabine, cytarabine, and paclitaxel) diluted in 5% dextrose injection or 0.9% sodium chloride injection in 250-mL infusion bags. Infusion lines were flushed using 5% dextrose injection or 0.9% sodium chloride solution at 2 different flow rates. The remaining concentration of cytotoxics in the infusion line was measured by a validated high-performance liquid chromatography (HPLC) method after passage of every 10 mL of flushing volume until a total of 100 mL had been flushed through. RESULTS: All cytotoxics remained detectable even after line flushing with 80 mL of flushing solution (a volume 3-fold greater than the dead space volume within the infusion set). Gemcitabine and cytarabine were still quantifiable via HPLC even after flushing with 100 mL of solution. Efficacy of flushing was influenced by the lipophilicity of drugs but not by either the flushing solvent used or the flushing flow rate. After 2-fold dead space volume flushing, the estimated amount of drug remaining in the infusion set was within 0.19% to 0.56% of the prescribed dose for all 3 cytotoxics evaluated. CONCLUSION: Complete elimination of cytotoxics from an infusion line is an unrealistic objective. Two-fold dead space volume flushing could be considered optimal in terms of administered dose but not from an environmental contamination point of view. Even when flushed, the infusion set should still be considered a source of cytotoxic contamination.

Body Mass Index and Calprotectin Blood Level Correlation in Healthy Children: An Individual Patient Data Meta-Analysis.

BACKGROUND: Calprotectin (CP) is a protein complex involved in many inflammatory diseases. Obesity is characterized by low-grade inflammation and elevated circulating levels of calprotectin. However, associations between body mass index (BMI) and calprotectin levels have not been explored in otherwise healthy children. METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and Cochrane Library database up to July 2019. Healthy children's blood calprotectin values were extracted, and potential correlations were explored. RESULTS: A total of six studies that included data on 593 healthy children were identified. Median calprotectin value was 900.0 (482.0; 1700) ng·mL-1. Multivariable analysis showed no significant associations with age, sample type (serum vs. plasma), or sex. In contrast, a significant effect of BMI z-score (p < 0.001) emerged. Indeed, a positive correlation between BMI z-score and CP, was detected in girls (R: 0.48; p < 0.001) and boys (R: 0.39; p < 0.001). CONCLUSION: Calprotectin blood levels correlate with the degree of adiposity in healthy children, but are not affected by age, sex, or sample type (serum or plasma).

The Tissue-Engineered Tendon-Bone Interface: In Vitro and In Vivo Synergistic Effects of Adipose-Derived Stem Cells, Platelet-Rich Plasma, and Extracellular Matrix Hydrogel.

BACKGROUND: Suboptimal healing of the tendon-bone interface remains an unsolved problem. The authors hypothesized that (1) platelet-rich plasma and prolonged in vitro incubation will produce interface scaffolds with greater reseeding of viable adipose-derived stem cells; and (2) when implanted with extracellular matrix hydrogel, constructs will display superior in vivo strength repair and biocompatibility. METHODS: Achilles-calcaneal composite tendon-bone interface scaffold grafts were harvested from 30 Wistar rats. After physicochemical decellularization and lyophilization, scaffolds were revitalized in rat plasma or 100% activated rat platelet-rich plasma and reseeded with viable adipose-derived stem cells. For part 2 of the study, 90 Sprague-Dawley rats underwent reconstruction with one of five decellularized, lyophilized scaffold revitalization/reseeding conditions: (1) phosphate-buffered saline; (2) lyophilized, 100% activated platelet-rich plasma; (3) platelet-rich plasma and extracellular matrix hydrogel; (4) platelet-rich plasma and 14-day reseeding with ASC-luc2-eGFP cells; and (5) plasma, reseeding, and hydrogel. RESULTS: In part 1, platelet-rich plasma-revitalized grafts demonstrated greater live viable adipose-derived stem cell loads at 3, 7, and 14 days and total adipose-derived stem cell loads at 7 and 14 days with visibly greater live surface cellularity, layering, migration, and penetration. In part 2, bioluminescence imaging confirmed cell viability to day 22 after implantation. Biomechanical strength testing demonstrated a significant increase in ultimate failure load for reseeded groups compared with all other groups at week 2, whereas only reseeded grafts with hydrogel remained significantly stronger at weeks 4 and 8. Histologic examination demonstrated most increased tendinous cellular invasion and fibrocartilage repopulation at 8 weeks in the reseeded group with hydrogel. Masson trichrome staining demonstrated persistence of the scaffold structure at week 8 and blinded ImageJ analysis demonstrated significantly more type III collagen in the reseeded/hydrogel group at 2, 4, and 8 weeks. CONCLUSIONS: Decellularized lyophilized allogeneic tendon-bone interface scaffolds can be optimized by revitalization in platelet-rich plasma, reseeding with viable adipose-derived stem cells, and supplemented by an extracellular matrix tendon hydrogel at the time of implantation. When this is done, they display greater repair strength and biocompatibility.

A cladistic re-analysis of the Gadiformes (Teleostei, Paracanthopterygii) using three-item analysis.

In the present paper, we describe LisBeth, a newly published phylogenetic program. LisBeth implements the cladistic three-item analysis for systematics and biogeography. We show how LisBeth handles character representation, character analysis, exact search functions, reconstruction of the intersection tree and other features, such as retention index, completeness index, character history and link with other programs such as PAUP*, version 4.0b10, TNT and Xper2. Using LisBeth, we reanalyze the phylogeny based on morphological characters of the order Gadiformes (Teleostei, Paracanthopterygii) published by Endo (2002) and compare our results. We also describe the generation of hypotheses of homology following Endo's guidelines versus 3ia representation schemes. We compare the topologies of all results and show the implications of the interpretation of character history.

Influence of vitamins, trace elements, and iron on lipid peroxidation reactions in all-in-one admixtures for neonatal parenteral nutrition.

BACKGROUND: The purpose of this study was to evaluate the effect of vitamins, trace elements, or iron on lipid peroxidation in all-in-one parenteral nutrition (PN) admixtures for preterm neonates. METHODS: Malondialdehyde (MDA) concentrations were analyzed over a 24-hour period (H1-H24) in lipid-containing PN solutions that have a composition identical to that used in the routine clinical care of preterm infants. Six different solutions were prepared and evaluated when exposed to ambient light and light-protected conditions as follows: control (without vitamins [Vit], trace elements [TE], or iron [Fe] [Vit-TE-Fe-]), solution 1 (Vit+TE+Fe-), solution 2 (Vit+TE-Fe-), solution 3 (Vit-TE+Fe-), solution 4 (Vit-TE-Fe+), and solution 5 (Vit+TE+Fe+). RESULTS: MDA concentrations in PN solutions were significantly higher at H24 than at H0 when they contained multivitamins (P < .001), trace elements (P = .002), or iron saccharate (P = .018). MDA concentration was particularly high when all 3 micronutrients were present (P < .001) or when the solutions were exposed to ambient light. In solutions containing iron, MDA concentrations were elevated at H0, and levels did not change whether protected from (P < .001) or exposed to (P < .001) from light. CONCLUSIONS: The addition of vitamins and trace elements to PN solutions induces a significant increase in peroxidation products, which are lowered when admixtures are protected from light. Iron should not be included in these solutions, even if solutions are light-protected. By following these conditions it is possible to use all-in-one admixtures in the nutrition management of preterm infants.