BackgroundEvidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed.MethodsThis was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables.ResultsFirst, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity.ConclusionThese results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1345-y) contains supplementary material, which is available to authorized users.

Objectives To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. Methods Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud—which includes scientific, peer-reviewed journals not indexed by other databases—were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. Results From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. Conclusions Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

Objectives: Pen devices offer advantages compared with vial and syringe (VaS). The purpose of this article was to evaluate efficacy of pen devices compared to VaS. Methods: A systematic review of literature was performed in 8 different databases. References were independently screened and selected. Primary observational or experimental studies comparing pen devices with VaS for insulin administrations were included. Studies on specific populations were excluded. Risk of bias was evaluated using appropriate tools. Data on glycosylated hemoglobin (HbA1c), hypoglycemia, adherence, persistence, patient preference, and quality of life (QOL) were collected. Meta-analysis was performed when appropriate. Heterogeneity and risk of publication bias were evaluated. Otherwise, descriptive analyses of the available data was done. Results: In all, 10 348 articles were screened. A total of 17 studies were finally selected: 7 experimental and 10 analytical. The populations of the included articles were mainly composed of adults with type 2 diabetes mellitus. Important risk of bias was found in all of the articles, particularly experimental studies. Meta-analyses were performed for HbA1c, hypoglycemia, adherence and persistence. Pen device showed better results in mean HbA1c change, patients with hypoglycemia, adherence and persistence compared to VaS. No difference was observed in number of patients achieving <7% HbA1c. Preference studies showed a tendency favoring pen devices, however nonvalidated tools were used. One QoL study showed improvements in some subscales of SF-36. Conclusions: There is evidence that pen devices offer benefits in clinical and, less clearly, patient-reported outcomes compared to VaS for insulin administration. However, these results should be taken with caution.

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