ROMP of novel hindered phenol-functionalized norbornenes and preliminary evaluation as stabilizing agents†

A series of new norbornene monomers containing sterically hindered phenol groups have been synthesized and polymerized via ring-opening metathesis polymerization (ROMP) using the Grubbs 3rd generation catalyst (G3’). ROMPs exhibit first-order kinetics and molar masses increase linearly with monomer conversion and well-controlled phenol hindered-functionalized polynorbornenes were obtained with a monomer to initiator ratio up to 1 000. The first-order rate constants show that the ROMP activity is closely associated with the norbornene monomer steric congestion. The antioxidant behavior of these hindered phenol-containing polynorbornenes with different para-bridged side groups in polypropylene (PP) was estimated by onset oxidation temperature (OOT) measurements. The ability of these hindered phenol-containing norbornenes to copolymerize by ROMP with dicyclopentadiene (DCPD) was used to bound covalently the antioxidant moiety onto a polydicyclopentadiene (PDCPD) resin whose thermal ageing has been investigated.We thank Mireille Barthe and Alexandre Bénard for SEC analyses and Sullivan Bricaud for NMR analyses. We acknowledge finan- cial support from Le Mans University, CNRS, and the French National Research Agency (VRPOM project, ANR-15-CE08-0025)

Enhance quality care performance: Determination of the variables for establishing a common database in French paediatric critical care units

Abstract Selected variables for the French Paediatric Intensive Care registry. Rationale, aims, and objectives Providing quality care requires follow-up in regard to clinical and economic activities. Over the past decade, medical databases and patient registries have expanded considerably, particularly in paediatric critical care medicine (eg, the Paediatric Intensive Care Audit Network (PICANet) in the UK, the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry in Australia and New Zealand, and the Virtual Paediatric Intensive Care Unit Performance System (VPS) in the USA). Such a registry is not yet available in France. The aim of this study was to determine variables that ought to be included in a French paediatric critical care registry. Methods Variables, items, and subitems from 3 foreign registries and 2 French local databases were used. Items described each variable, and subitems described items. The Delphi method was used to evaluate and rate 65 variables, 90 items, and 17 subitems taking into account importance or relevance based on input from 28 French physicians affiliated with the French Paediatric Critical Care Group. Two ratings were used between January and May 2013. Results Fifteen files from 10 paediatric intensive care units were included. Out of 65 potential variables, 48 (74%) were considered to be indispensable, 16 (25%) were considered to be optional, and 1 (2%) was considered to be irrelevant. Out of 90 potential items, 62 (69%) were considered to be relevant, 23 (26%) were considered to be of little relevance, and 5 (6%) were considered to be irrelevant. Out of 17 potential subitems, 9 (53%) were considered to be relevant, 6 (35%) were considered to be of little relevance, and 2 (12%) were considered to be irrelevant. Conclusions The necessary variables that ought to be included in a French paediatric critical care registry were identified. The challenge now is to develop the French registry for paediatric intensive care units

Thermal oxidation of poly(Dicyclopentadiene) – Decomposition of hydroperoxides

Thin unstabilized PDCPD film were thermally oxidized in ovens at several temperatures ranging from 50 °C to 120 °C. Hydroperoxide concentration was monitored by DSC. It was observed that hydroperoxides concentration reaches a plateau with short induction times, for example around 8 h at 50 °C. This plateau occurs at very high concentration, around about 1 mol l−1 at 50 °C. In order to study both the chemical mechanisms and the kinetics of hydroperoxides decomposition, oxidized samples were thermally aged in an inert atmosphere to destroy hydroperoxides. For initially high concentrations corresponding to the “plateau”, it was shown that hydroperoxides decompose following a bimolecular process, the rate constant of which being calculated from the hydroperoxide depletion curves. The comparison of samples containing different polymerization catalyst amounts suggested the co-existence of an unimolecular process. This process mainly occurs at low hydroperoxides concentrations and slightly influences the overall oxidation process

Kinetic analysis of polydicyclopentadiene oxidation

The in situ thermal oxidation of thin unstabilized polydicyclopentadiene was studied by TGA to monitor mass gain, and DSC to characterize hydroperoxides concentration. Results were discussed using kinetic analysis, which allowed the estimation of activation energies for key reactions of the oxidation process. Activation energy for termination was shown to be higher than in hydrocarbon liquids, which was discussed from the theory of diffusion controlled reactions, and a possible link with local motions associated with sub-glassy transition. Activation energy of thermal decomposition of hydroperoxides was found lower than for model hydroperoxides, suggesting an accelerating effect of organometallic catalysts. Despite those two results that indicate a poor thermal stability of thin pDCPD films, measurements of oxygen diffusivity at several temperatures show that oxidation remains confined in a relatively thin surface layer which would allow the pDCPD properties to be preserved

Enhanced thermo-oxidative stability of polydicyclopentadiene containing covalently bound nitroxide groups

The antioxidant 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) group was covalently introduced into polydicyclopentadiene (PDCPD) through ring-opening metathesis polymerization (ROMP) copolymerization of dicyclopentadiene (DCPD) with a TEMPO-derived norbornene comonomer. The thermal oxidation of the resulting thin films was monitored by ThermoGravimetric Analyses (TGA) and Fourier-Transform Infra-Red spectroscopy (FT-IR). This new PDCPD stabilized by immobilization of the TEMPO antioxidant shows a better thermo-oxidative stability at 60 °C under air than an industrial formulation of PDCPD stabilized with 2,6-di‑tert‑butyl‑4-methylphenol (BHT). Impact of thermal oxidation on mechanical behaviour of both formulations have been studied by tensile tests and fracture tests, based on the essential work of fracture (EWF) concept. The TEMPO-functionalized PDCPD offers a promising alternative to BHT-stabilized PDCPD with comparable ductility but slower decay and better cracking resistance, confirming the benefit of the TEMPO antioxidant in PDCPD formulation when chemically bound to the matrix

Primary bone diffuse large B-cell lymphoma: a retrospective evaluation on 76 cases from French institutional and LYSA studies

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease

A 4-weekly course of rituximab is safe and improves tumor control for patients with minimal residual disease persisting 3 months after autologous hematopoietic stem-cell transplantation: results of a prospective multicenter phase II study in patients with follicular lymphoma.

International audienceBACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control

MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499