Abstract Objectives To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a biologic ...DMARD (bDMARD) in the treatment of early rheumatoid arthritis. Methods A systematic literature search was performed using the PubMed and Cochrane databases, and abstracts presented at rheumatology scientific meetings until December 2013. Randomized controlled trials comparing the efficacy and the safety of biologic DMARD with the triple combination were included. Outcome measures were Van der Heijde modified Sharp score (SHS), remission rate, ACR criteria response, adverse events. Results A total of 1225 abstracts were screened. We extracted data from 5 trials including patients (515 in the triple combination group and 710 in the bDMARD group). We showed higher ACR70 response (OR = 1.79, 95% CI 1.17, 2.72) in patients treated with bDMARDs, whereas radiological progression was not different from patient with triple combination (OR = 1.10, 95% CI –0.04, 0.28). At year 2, ACR70 response and remission rate, the results were similar in both groups with respectively OR = 1.44 (95% CI 0.86, 2.43) and SMD = 0.45 (95% CI 0.17, 0.72). The proportion of serious adverse events was similar in both groups OR = 1.02 (95% CI 0.68, 1.52, P = 0.92, I2 = 0%). Gastro-intestinal adverse events were higher in the triple combination group (OR = 1.75, 95% CI 0.73, 4.21, P = 0.21, I2 = 75%). Infectious adverse events were more frequent in the bDMARD group (OR = 0.50, 95% CI 0.35, 0.70, P < 0.0001, I2 = 36%). Conclusion Biological treatment seems to be more efficient than triple combination in terms of radiological progression in RA with inadequate response to methotrexate.
•Strategies aimed at improving medication adherence are of central important to prevent relapse and enhance prognosis of patients suffering from schizophrenia.•When using electronic medication ...monitoring as an objective measure of adherence, easily-implemented or lower-cost strategies may not result in significant improvements in adherence in community-dwelling patients at high risk for relapse.•The promising findings observed for previous adherence interventions should be pursued with a greater emphasis on new tools that improve reporting accuracy.
Poor medication adherence remains frequent in schizophrenia. The present study examined the efficacy of two month-long pilot interventions using the Medication Event Monitoring System (MEMS®). Thirty-three outpatients at high risk for relapse were randomized to receive a smartphone-based intervention, a nurse-based intervention, or treatment as usual. All patients then used the MEMS® to objectively measure medication adherence over six months. No differences were observed in adherence measures or relapse rates across the three groups. When using electronic medication monitoring as an objective measure of adherence, easily-implemented interventions may not significantly improve adherence in patients at high risk for relapse.
Risk-based approaches to managing allergens in foods are being developed by the food industry and regulatory authorities to support food-allergic consumers to avoid ingestion of their problem food, ...especially in relation to the traces of unintended allergens. the application of such approaches requires access to good quality data from clinical studies to support identification of levels of allergens in foods that are generally safe for most food-allergic consumers as well as analytical tools that are able to quantify allergenic food protein. the ThRAII project aims to support the application of risk-based approaches to food-allergen management in two ways. First, a harmonized quantitative MS-based prototype reference method will be developed for the detection of multiple food allergens in standardized incurred food matrices. This will be undertaken for cow's milk, hen's egg, peanut, soybean, hazelnut, and almond incurred into two highly processed food matrices, chocolate and broth powder. This activity is complemented by a second objective to support the development and curation of data on oral food challenges, which are used to define thresholds and minimum eliciting doses. This will be achieved through the development of common protocols for collection and curation of data that will be applied to allergenic foods for which there are currently data gaps.
Abstract Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence ...support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190 mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.
Lymphatic endothelium serves as a barrier to control fluid balance and immune cell trafficking to maintain tissue homeostasis. Long-term alteration of lymphatic vasculature promotes edema and ...fibrosis, which is an aggravating factor in the onset of cardiovascular diseases such as myocardial infarction. Apelin is a bioactive peptide that plays a central role in angiogenesis and cardiac contractility. Despite an established role of apelin in lymphangiogenesis, little is known about its function in the cardiac lymphatic endothelium. Here, we show that apelin and its receptor APJ were exclusively expressed on newly formed lymphatic vasculature in a pathological model of myocardial infarction. Using an apelin-knockout mouse model, we identified morphological and functional defects in lymphatic vasculature associated with a proinflammatory status. Surprisingly, apelin deficiency increased the expression of lymphangiogenic growth factors VEGF-C and VEGF-D and exacerbated lymphangiogenesis after myocardial infarction. Conversely, the overexpression of apelin in ischemic heart was sufficient to restore a functional lymphatic vasculature and to reduce matrix remodeling and inflammation. In vitro, the expression of apelin prevented the alteration of cellular junctions in lymphatic endothelial cells induced by hypoxia. In addition, we demonstrated that apelin controls the secretion of the lipid mediator sphingosine-1-phosphate in lymphatic endothelial cells by regulating the level of expression of sphingosine kinase 2 and the transporter SPNS2. Taken together, our results show that apelin plays a key role in lymphatic vessel maturation and stability in pathological settings. Thus, apelin may represent a novel candidate to prevent pathological lymphatic remodeling in diseases.
Abstract
Aims
The effect of MitraClip implantation on left ventricular (LV) remodelling has been shown to be highly variable. The present study wants to assess patterns of LV remodelling and its ...relationship with outcome.
Methods and results
Serial echocardiography before, 1 and 6 months after MitraClip implantation was performed in 79 pts with severe mitral regurgitation (MR) (age 74 ± 10 years, New York Heart Association III/IV 80%, LV ejection fraction 38 ± 13%, logistic EuroSCORE 21 ± 15, and functional MR 81%). LV reverse/adverse remodelling was defined as a >15% decrease/>10% increase in LV end-diastolic volume (LVEDV), respectively. Patients were followed over a period of 32 ± 16 months with all-cause mortality as the primary endpoint. A sustained (6 month) reduction of MR ≤ 2 post-MitraClip implantation was observed in 83% of patients. The average decrease in LVEDV 6 months after intervention was 13% ± 16%. Reverse remodelling at 6 months occurred in 40 patients (51%), and adverse remodelling occurred in 6 patients (8%). Patients with adverse remodelling showed a 38% increase of LVEDV at 1 month vs. no early change in LVEDV in patients with reverse remodelling. During follow-up, a total of 25 patients (32%) died. Patients with adverse remodelling died more frequently than patients with reverse remodelling 67% vs. 27%, adjusted odds ratio of 5.6 (95% CI 1.5–21).
Conclusion
The majority of patients undergoing MitraClip implantation for severe MR showed LV reverse remodelling. However, there was a small group in whom afterload mismatch resulted in sustained adverse remodelling with subsequent high mortality.
BLyS and APRIL share two receptors – transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B‐cell maturation antigen (BCMA) – and BLyS binds to a third receptor, ...BAFF‐R. We previously reported that TACI gene expression is a good indicator of a BLyS‐binding receptor in human multiple myeloma cell lines (HMCLs), unlike BCMA, which is expressed by all HMCLs or BAFF‐R which is typically not expressed by late‐stage B cells. We hypothesised a link between APRIL and TACI through syndecan‐1, similar to the situation reported for FGF and FGFR. We observed very strong binding of APRIL, but not BLyS, at the surface of all syndecan‐1+ HMCLs and primary multiple myeloma cells (MMC). All syndecan‐1+ HMCLs and MMC could also bind TACI‐Fc, but not BCMA‐Fc or BAFF‐R‐Fc molecules. Binding of APRIL or TACI‐Fc was abrogated by heparin or cell pretreatment with heparitinase, which cleaves heparan sulfate chains. The growth factor activity of APRIL on MMC was also inhibited by heparin. Our data identify syndecan‐1 as a co‐receptor for APRIL and TACI at the cell surface of MMC, promoting the activation of an APRIL/TACI pathway that induces survival and proliferation in MMC.
Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical ...trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest. Mono- and multicistronic lentivectors expressing fibroblast growth factor 2 (angiogenesis), apelin (cardioprotection), and/or SERCA2a (contractile function) were produced and administrated by intramyocardial injection into a mouse model of myocardial infarction. Data reveal that combined treatment simultaneously improves vessel number, heart function parameters, and fibrosis prevention, due to FGF2, SERCA2a, and apelin, respectively. Furthermore, addition of SERCA2a in the combination decreases cardiomyocyte hypertrophy. Large-scale transcriptome analysis reveals that the triple treatment is the most efficient in restoring angiogenic balance as well as expression of genes involved in cardiac function and remodeling. Our study validates the concept of combined treatment of ischemic heart disease with apelin, FGF2, and SERCA2a and shows that such therapeutic benefit is mediated by a more effective recovery of gene network regulation.
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A.-C. Prats and co-authors demonstrate the therapeutic benefit of an IRES-based lentivector co-expressing FGF2, apelin, and SERCA2a to treat ischemic heart disease in a mouse model of infarcted myocardium. This therapeutic molecule combination acts by restoring the angiogenic balance as well as heart function and fibrosis gene network regulation.
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