Data integration,analysis, and interpretation of eight academic CLARITY-BPA studies

“Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA) was a comprehensive “industry-standard” Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically – and toxicologically – relevant.     

Autoimmune disease in CMML-the chicken or the egg?

Chronic myelomonocytic leukemia (CMML) is a clonal disorder that is associated with a wide range of systemic inflammatory and autoimmune diseases (SIADs). Approximately 20% of patients with CMML will have an associated SIAD and recognizing this association is critical to the evaluation, prognostication and management of patients with CMML. In this paper, we review the evidence supporting a causative link between these two entities as well as the direction of this relationship. We argue that the data favors CMML as the antecedent and causative disease state with a few notable exceptions. Better understanding of this relationship aids clinicians in the education of their patients and in determining the optimal management approach at the bedside. It is important to recognize opportunities to harmonize the treatments of these disease processes, which may enhance the effectiveness of treatment while reducing the burden of adverse effects from redundant therapies.     

Causas de mortalidad asociadas a enfermedad reumática autoinmune en un hospital de referencia

The causes of mortality among rheumatic diseases vary widely between geographic areas and cannot be generalized, however, they are frequently associated with the aggressiveness of the clinical presentation and the secondary effects of the therapy used. The main purpose of this study was to characterize the causes of death in a group of patients with autoimmune rheumatic disease. For this purpose, a retrospective study was carried out over a period of 10 years (2009 to 2019), deceased patients were included from a referral centre in Guatemala City, the records were reviewed in search of demographic and clinical variables. In total, 185 deceased patients were identified from 898 admissions during that period, 85.9% were women and the main disease reported was systemic lupus erythematosus in 49.7% of the cases. Among the causes of mortality, infections were reported in 53% and those attributed to disease activity in 15% of cases. The main conclusion is that that most of the deaths were of infectious origin.     

Systemic sclerosis and exposure to heavy metals

As a mirror image of the Roman god Janus Bifrons, the environment has a hidden face. To highlight this hidden face of the environment in the field of systemic sclerosis (SSc) will allow to identify responsible agents emerging in the future. To date, there is, in fact, a growing scientific evidence that environmental factors have a crucial impact on both alterations and modulation of epigenetic determinants, resulting in SSc onset and progression. It has been well established that there is a marked correlation between SSc onset and occupational exposure to crystalline silica and organic solvents. More recently, an association between SSc and exposure to heavy metals has further been found, including: antimony, cadmium, lead, mercury. These latter findings interestingly underscore that occupational exposure to heavy metals should be systematically checked in all SSc patients at diagnosis, as the identification of the occupational toxic agent will allow its interruption, which may result in potential improvement of SSc outcome.     

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.