Management of ibrutinib treatment in patients with B-cell malignancies: clinical practice in Portugal and multidisciplinary recommendations

Objectives: Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies. Ibrutinib has an established favorable toxicity profile with up to 8 years of experience in clinical trials; however, despite ibrutinib’s favorable toxicity profile, dose reductions and treatment discontinuations are becoming more evident in clinical practice, particularly in the setting of specific clinical contexts and patient characteristics. This manuscript is set to provide practical recommendations on the management of patients treated with this agent in daily practice. Methods: A group of multidisciplinary experts from Portugal met to discuss and highlight practical recommendations, supported on both literature and clinical insights, for the management of the treatment with ibrutinib. Results/discussion: Handling of both toxicities and drug–drug interactions during ibrutinib treatment poses several challenges to healthcare providers and can benefit from a multidisciplinary approach. The involvement of specialties, such as cardiology, infectiology and pharmacology, can bring an added value to patient care, not only in anticipating/managing safety issues and dose adjustments but also in enhancing adherence to treatment, ultimately improving the risk/benefit balance. Conclusion: By involving a multidisciplinary group of experts, this work provides a set of key recommendations to optimize care and outcomes for ibrutinib-treated patients. Despite not being a fully comprehensive review on the topic, it is intended as a framework to hematologists and other healthcare professionals who manage these patients in their daily clinical practice.The project received financial support from Janssen for logistics of expert meetings and editorial support. The sponsor had no influence on the opinions expressed here, which are those of the authors

Valorization, comparison and characterization of coconuts waste and cactus in a biorefinery context using NaClO2-C2H4O2 and sequential NaClO2-C2H4O2/autohydrolysis pretreatment

The search for new sources of lignocellulosic raw materials for the generation of energy and new compounds encourages the search for locations not well known and with a high potential for biomass availability as is the case of the Northeast Region of Brazil. Thus, the cactus (CAC), green coconut shell (GCS), mature coconut fibre and mature coconut shell were pretreated by NaClO2C2H4O2 and sequential NaClO2C2H4O2/autohydrolysis aiming at the obtention of high added-value compounds in the liquid fraction and solid phase. The yield of the solid phase was between 61.42 and 90.97% and the reduction up to 91.63% of lignin in the materials pretreated by NaClO2C2H4O2. After NaClO2C2H4O2/autohydrolysis pretreatment the obtained solids yield was between 43.57 and 52.08%, with a solubilization of the hemicellulose content up to 81.42%. For both pretreatments the cellulosic content remained almost unchanged. The pretreated solids were characterized by SEM, X-ray and crystallinity indexes showing significant modifications when submitted to pretreatments. These results were further confirmed by the enzymatic conversion yields of 81.6890.03 and 86.9790.36% of the LCMs pretreated by NaClO2C2H4O2 and pretreated by NaClO2C2H4O2/autohydrolysis, respectively. The resulting liquors had a total phenolic compounds content between 0.20 and 3.05 g/L, lignin recovered up to 7.40 g/L (absence of sulphur) and xylooligosaccharides between 16.13 and 20.37 g/L. Thus, these pretreatments showed an efficient fractionation of LCMs, especially in the GCS, being an important requirement for the generation of products and byproducts in the context of the biorefinery.The authors gratefully acknowledge the Brazilian research funding agencies CNPq and CAPES for financial support. Financial support from the Energy Sustainability Fund 2014-05 (CONACYT-SENER), Mexican Centre for Innovation in Bioenergy (CemieBio), Cluster of Bioalcohols (Ref. 249564) is gratefully acknowledged. We also gratefully acknowledge support for this research by the Mexican Science and Technology Council (CONACYT, Mexico) for the infrastructure project - INFR201601 (Ref. 269461) and CB-2015-01 (Ref. 254808).info:eu-repo/semantics/publishedVersio

Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes.

Published onlineJournal ArticleThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006, the Swedish Heart-Lung Foundation, the Swedish Research Council and Marianne and Marcus Wallenberg Foundation)

Pathogen-Specific Epitopes as Epidemiological Tools for Defining the Magnitude of Mycobacterium leprae Transmission in Areas Endemic for Leprosy

During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population