Trained immunity is a process in which innate immune cells undergo functional reprogramming in response to pathogens or damage‐associated molecules leading to an enhanced non‐specific immune response to subsequent stimulation. While this capacity to respond more strongly to stimuli is beneficial for host defense, in some circumstances it can lead to maladaptive programming and chronic inflammation. Gout is characterized by persistent low‐grade inflammation and is associated with an increased number of comorbidities. Hyperuricemia is the main risk factor for gout and is linked to the development of comorbidities. Several experimental studies have shown that urate can mechanistically alter the inflammatory capacity of myeloid cells, while observational studies have indicated an association of hyperuricemia to a wide spectrum of common adult inflammatory diseases. In this review, we argue that hyperuricemia is a main culprit in the development of the long‐term systemic inflammation seen in gout. We revisit existing evidence for urate‐induced transcriptional and epigenetic reprogramming that could lead to an altered functional state of circulating monocytes consisting in enhanced responsiveness and maladaptive immune responses. By discussing specific functional adaptations of monocytes and macrophages induced by soluble urate or monosodium urate crystals and their contribution to inflammation in vitro and in vivo, we further enforce that urate is a metabolite that can induce innate immune memory and we discuss future research and possible new therapeutic approaches for gout and its comorbidities.

There is a consistent relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. It is already recognized that OSA may influence the geometry and function of the right ventricle (RV). This has encouraged the development of echocardiographic evaluation for screening of OSA and its severity. Three-dimensional speckle tracking echocardiography (3D STE) is in assumption better, compared with 2D STE, because it overcomes the standard 2D echo limitations. Thus, the purpose of our study is to evaluate whether 3D STE measurements, could predict the positive diagnosis and severity of OSA. We enrolled 69 patients with OSA and 37 healthy volunteers who underwent a cardiorespiratory sleep study. 2DE was performed in all patients. RVEF and 3D RVGLS were measured by 3DSTE. NT pro BNP plasma level was also assessed in all participants. 3D RV GLS (− 13.5% vs. − 22.3%, p < 0.001) and 3D RVEF (31.9% vs. 50%, p < 0.001) were reduced in patients with OSA, compared with normal individuals. 3D Strain parameters showed better correlation to standard 2D variables, than 3D RVEF. Except for NT pro BNP (p = 0.059), all parameters served to distinguish between severe and mild-moderate cases of OSA. 3D STE may be a reliable and accurate method for predicting OSA. Consequently, 3D RV GLS is a good tool of assessing the RV global function in OSA, because it correlates well with other established measurements of RV systolic function. Furthermore, 3D RV GLS was a precise parameter in identifying severe cases of OSA, while NT pro BNP showed no association.

Background: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven in randomized controlled trials to be an effective therapy for this condition. The impact of CPAP on the cardiovascular pathology associated with OSA remains, however, unclear. Although the effect of CPAP has been previously studied in relation to cardiovascular outcome, follow-up of the treatment impact on cardiovascular risk factors at one year of therapy is lacking in a Romanian population. Thus, we aimed to evaluate the one-year effect of CPAP therapy on lipid profile, inflammatory state, blood pressure and cardiac function, assessed by echocardiography, on a cohort of Romanian OSA patients. Methods: We enrolled 163 participants and recorded their baseline demographic and clinical characteristics with a follow-up after 12 months. Inflammatory and cardiovascular risk factors were assessed at baseline and follow up. Results: Our results show that CPAP therapy leads to attenuation of cardiovascular risk factors including echocardiographic parameters, while having no effect on inflammatory markers. Conclusion: Treatment of OSA with CPAP proved to have beneficial effects on some of the cardiovascular risk factors while others remained unchanged, raising new questions for research into the treatment and management of OSA patients.

Introduction: GAD2 gene encodes the glutamate decarboxylase enzyme which catalyses the transformation of glutamate into γ-aminobutyric acid, GABA. It is suggested that some polymorphic alleles of GAD2 gene, such as -243A>G, have an increased transcriptional effect compared with the wild type, which results in an increase of GABA in the hypothalamus with the subsequent increase of the neuropeptide Y, thus exacerbating the hunger centre and the appetite. The aim of this study was to observe an association between the -243A>G polymorphism with obesity, comparatively studying a group of obese patients and a group of patients with normal weight. Patients and method: 127 patients were clinically evaluated in the Genetic and Endocrine Department of Children’s Emergency Clinical Hospital, Cluj. The patients were included in two study groups, case group, with obesity (BMI higher than 97 kg/m2) and control group, with normal weight (BMI less than 97 kg/m2). Genotyping for GAD2-243A>G polymorphism was performed using PCR-RFLP technique, the two groups being compared regarding the genotypes and phenotypes. Results and conclusions: In the obesity group, there is a statistically significant difference in BMI (kg/m2) between the subgroups with different genotypes (p=0.01), the AA genotype being less severely affected than AG and GG genotypes. In the normal weight group there is no association between BMI and different genotypes (AA, AG or GG). Also, there is a greater distribution of GG genotypes and G allele in the obesity group compared with the control group, with an odds ratio which suggest that -243A>G polymorphism is a risk factor in obesity development (GG genotype OR=3.76, G allele OR=1.73, p=0.04). The finding of our study is important in explaining the multifactorial model of obesity, our research demonstrating that the GAD2-243 A> G variant could be a risk factor that added to other obesogenic factors would potentiate their effect.

Background Soluble urate leads to a pro-inflammatory phenotype in human monocytes characterized by increased production of IL-1β and downregulation of IL-1 receptor antagonist, the mechanism of which remains to be fully elucidated. Previous transcriptomic data identified differential expression of genes in the transforming growth factor (TGF)-β pathway in monocytes exposed to urate in vitro. In this study, we explore the role of TGF-β in urate-induced hyperinflammation in peripheral blood mononuclear cells (PBMCs). Methods TGF-β mRNA in unstimulated PBMCs and protein levels in plasma were measured in individuals with normouricemia, hyperuricemia and gout. For in vitro validation, PBMCs of healthy volunteers were isolated and treated with a dose ranging concentration of urate for assessment of mRNA and pSMAD2. Urate and TGF-β priming experiments were performed with three inhibitors of TGF-β signalling: SB-505124, 5Z-7-oxozeaenol and a blocking antibody against TGF-β receptor II. Results TGF-β mRNA levels were elevated in gout patients compared to healthy controls. TGF-β-LAP levels in serum were significantly higher in individuals with hyperuricemia compared to controls. In both cases, TGF-β correlated positively to serum urate levels. In vitro, urate exposure of PBMCs did not directly induce TGF-β but did enhance SMAD2 phosphorylation. The urate-induced pro-inflammatory phenotype of monocytes was partly reversed by blocking TGF-β. Conclusions TGF-β is elevated in individuals with hyperuricemia and correlated to serum urate concentrations. In addition, the urate-induced pro-inflammatory phenotype in human monocytes is mediated by TGF-β signalling. Future studies are warranted to explore the intracellular pathways involved and to assess the clinical significance of urate-TGF-β relation.