Effect of the plasticizer on permeability, mechanical resistance and thermal behaviour of composite coating films

Thin layer deposit of a composite material on solid particle surfaces used in the food industry aims to ensure the protection of food powder against aggressive environments such as amoist atmosphere. The layer, having a thickness of a few fractions of millimetre, must have certain physico-chemical properties: it must be compatible with the product, itmust be impermeable to water and oxygen, itmust have goodmechanical strength and good adhesion to the surface of the coated powder. Furthermore the layer must fulfil the regulatory requirements for food ingredients. Film properties like continuity, permeability, and mechanical resistance depend on the choice of the excipients included in the formulation and the operating conditions which can modify the constraints generated at the interface film-powder. As a consequence, the scientific issue consists of combining the local phenomena happening at amicroscopic level on the surface of the particle with the processing technology and the process parameters. In a first step, the attention is focussed on the film and its formulation. For this step, films are prepared separately and they are dried under very smooth conditions. Test samples are taken from the formed composite films and contain hydroxypropyl methylcellulose asmatrix (67% of driedmaterial),micronised stearic acid as hydrophobic filler (20% of driedmaterial) and a plasticizer (13% of driedmaterial). The filmformation procedure and the testmethod are described in detail. The effect of the type of plasticizer (different grades of PEG) onmechanical, thermal and permeability properties of the coating film is studied. The results show that PEG with higher molecular rate provides a better plasticizing effect for the film but increases the water vapour permeability of the film

Outcome of COVID-19 in Patients With Mantle Cell Lymphoma-Report From the European MCL Registry

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort

Parkinsonian Patients Requiring Proteasome Inhibitors for Multiple Myeloma: Exceptional Circumstances Call for Extra Caution

Feedback on the management of patients with both Parkinson’s disease (PD) and multiple myeloma (MM) is not common in the literature, and we would like to report an original possible adverse event (AE) of MM chemotherapy: an increased PD severity induced by ixazomib. The patient, a 68-year-old man with PD (Hoehn and Yahr (HY) stage 3) was effectively and stably treated for 14 years with dopaminergic therapy (levodopa equiva25 lent daily dose (LEDD) 1275 mg). His symptomatic MM was first treated by lenalidomide (25 mg) with dexamethasone (Rd protocol) for 19 months. Then, a second-line therapy combined the proteasome inhibitor (PI) ixazomib (4 mg) with lenalidomide (20 mg) and dexamethasone (IRd protocol, 4-week cycle) due to MM progression

Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

International audienceIntroductionImmune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring.MethodsAll the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included.ResultsSeveral medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies.ConclusionThis detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.IntroductionL’immunomonitoring des anticorps monoclonaux représente une aide pour la prise en charge des patients sous anti-Tumor Necrosis Factor-α, en particulier en gastro-entérologie. En revanche, pour les autres anticorps monoclonaux, dont le rituximab, pourtant utilisé depuis près de quinze ans en auto-immunité, les études évaluant l’intérêt de ce monitoring sont quasiment absentes. Ainsi, l’objectif de cette étude était de décrire les caractéristiques clinicobiologiques des patients pour lesquels un immunomonitoring du rituximab a été prescrit dans notre centre.MéthodesLes données cliniques, biologiques et thérapeutiques disponibles pour les demandes d’immunomonitoring du rituximab (dosages de la rituximabémie et des anticorps antirituximab par une technique « sensible au médicament » LISA-TRACKER Duo Rituximab®) reçues depuis 2015 ont été analysées rétrospectivement. Les suspicions d’hypersensibilité et les non-réponses secondaires ont été incluses.RésultatsSur les 23 demandes reçues, 18 dossiers ont été inclus, impliquant plusieurs spécialités (néphrologie, hématologie, neurologie, rhumatologie, médecine interne), avec 10 suspicions d’hypersensibilité et 8 non-réponses secondaires. Les 6 patients dont la présentation clinique était évocatrice de maladie sérique, ainsi que la moitié des cas de non-réponse secondaire, étaient positifs pour les anticorps anti-rituximab.ConclusionL’analyse des différentes situations cliniques présentées ici ayant conduit à une demande d’immunomonitoring du rituximab suggère que cet examen (en particulier la recherche d’anticorps antirituximab) serait intéressant en cas de suspicion de maladie sérique et/ou de non-réponse secondaire (notamment en l’absence de déplétion lymphocytaire B), et mériterait d’être étudié via des études prospectives de grande taille

Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells

Background: Multiple myeloma (MM) is the second most common hematological cancer after lymphoma. It is characterized by the accumulation of clonal malignant plasma cells within the bone marrow. The development of drug resistance remains a major problem for effective treatment of MM. Understand the mechanisms underlying drug resistance in MM is a focal point to improve MM treatment. Methods: In the current study, we analyzed further the role of redox imbalance induction in melphalan-induced toxicity both in human myeloma cell lines (HMCLs) and primary myeloma cells from patients. Results: We developed an in-vitro model of short-term resistance to high-dose melphalan and identified that pretreatment with physiological concentration of GSH protects HMCLs from melphalan-induced cell cycle arrest and cytotoxicity. We validated these results using primary MM cells from patients co-cultured with their bone marrow microenvironment. GSH did not affect the ability of melphalan to induce DNA damages in MM cells. Interestingly, melphalan induced reactive oxygen species, a significant decrease in GSH concentration, protein and lipd oxydation together with NRF2 (NF-E2-related factor 2) pathway activation. Conclusions: Our data demonstrate that antioxidant defenses confers resistance to high dose melphalan in MM cells, supporting that redox status in MM cells could be determinant for patients’ response to melphalan

Cancer incidence in primary Sjögren's syndrome: Data from the French hospitalization database

International audienceThe relationship between cancer and primary Sjögren's syndrome (pSS) is uncertain. While the increased risk of hematological malignancies is well-known, data on the comparative incidence of solid neoplasms is conflicting. This study aimed to explore the associations between cancer and pSS. This nationwide population-based retrospective study from the French health insurance database (PMSI) evaluated patients hospitalized with new-onset pSS from 2011 to 2018 against age- and sex-matched hospitalized controls (1:10). The incidence of hematological malignancies and solid neoplasms was compared between the two groups. Mortality and multiple cancer incidence were also evaluated. Adjusted Hazard Ratios (aHR) calculations included confounding factors, such as low socioeconomic status. Among 25,661 hospitalized patients with pSS versus 252,543 matched patients (median follow-up of 3.96 years), we observed a higher incidence rate of lymphomas (aHR, 1.97 [95% CI, 1.59-2.43]), Waldenström macroglobulinemia (aHR, 10.8 [6.5-18.0]), and leukemia (aHR, 1.61 [1.1-2.4]). Thyroid cancer incidence was higher (aHR, 1.7 [1.1-2.8]), whereas bladder and breast cancer incidences were lower (aHR, 0.58 [0.37-0.89] and 0.60 [0.49-0.74], respectively). pSS patients with breast cancer exhibited a lower mortality rate. A limitation was that the database only encompasses hospitalized patients, and immunological and histological details are not listed. We confirmed the increased risk of hematological malignancies and thyroid cancers among patients with pSS. The lower risk of breast cancer suggests a role of hormonal factors and raises questions of the concept of immune surveillance within breast tissue. Epidemiological and translational studies are required to elucidate the relationships between pSS and cancer

Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study

International audienceBackgroundPatients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality.MethodsThis retrospective multicentric cohort study used the Programme de Médicalisation des Systèmes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts.FindingsEighty-nine patients were included. The median age was 67 years (range, 19–92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62–81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20–6·85, p = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14–5·66, p = 0·02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3·20, 1·33–7·72, p = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%).InterpretationThirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population

Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy

International audienceProlonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population

Donor Lymphocyte Infusions (DLI): Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Les injections de lymphocytes du donneur (DLI) peuvent être proposées pour traiter ou prévenir la rechute d’une hémopathie maligne après allogreffe de cellules souches hématopoïétiques. L’efficacité est principalement rapportée dans le traitement de la leucémie myéloïde chronique et les lymphomes à caractère indolent. L’activité antitumorale est moindre pour les leucémies aiguës et les syndromes myélodysplasiques. L’effet bénéfique « greffon versus leucémie » (GVL) doit toujours être évalué par rapport à la morbi-mortalité possible liée à la réaction du greffon contre l’hôte (GVHD). Les premières recommandations de la SFGM-TC de 2013 concernant l’utilisation des DLI sont mises à jour. Les doses de DLI dans le cadre des greffes haplo-identiques sont indiquées. L’excédent de cellules souches périphériques mobilisées par rhG-CSF peut être utilisé comme DLI. La définition et la place des DLI préemptives et prophylactiques sont précisées. Des recommandations sont également proposées concernant l’évaluation de la qualité des DLI décongelées et le suivi clinique et biologique après DLI.Donor lymphocyte infusion (DLI) can be proposed to treat or prevent the relapse of malignant hemopathies following allogeneic stem cell transplantation. The efficiency has been mainly reported in the treatment of CML and low-grade lymphomas while the anti-tumoral activity is less in forms of acute leukemia and myelodysplastic syndromes. The GVL benefit should always be compared to the possible toxic effects of GVHD. This article updates the initial SFGM-TC recommendations, proposed in 2013, that were focused on the use of DLI. Doses of DLI in the context of haplo-identical stem cell transplantation are now indicated. We confirm that remaining mobilized stem cells may be used as classical DLI. The definition and the place of preemptive and prophylactic DLI are precisely given. Recommendations regarding the quality of thawed DLI as well as necessary clinical and biological follow-up are also described in detail