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Objectives To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease ( MD) and to compare them with the clinical subgroups found in bilateral MD. Design A cross-sectional study with a two-step cluster analysis. Settings A tertiary referral multicenter study. Participants Nine hundred and eighty-eight adult patients with unilateral MD. Main outcome measures: best predictors to define clinical subgroups with potential different aetiologies. Results We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder ( AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Conclusions Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. [ABSTRACT FROM AUTHOR]

Background Patients with systemic lupus erythematosus (SLE) have a higher risk for cardiovascular disease (CVD), not fully explained by the conventional risk factors. These patients have endothelial dysfunction (ED) as an early process of atherosclerosis, which can be reversed with therapy. Objective To determine the effect of ezetimibe plus pravastatin on endothelial function in patients with SLE after 12 months of treatment. Patients and methods An open study, before and after, which assessed the effect of ezetimibe plus pravastatin treatment, was performed. Twenty two patients (21 women and one man) with diagnosis of SLE were studied, with a mean age 40 ± 5 years. Endothelial dysfunction was evaluated using vascular ultrasound of the brachial artery in order to measure the flow-mediated vasodilation (FMV) basal and after 12 months of treatment with pravastatin 40 mg/day plus ezetimibe 10 mg/day. In addition, a lipid profile: total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and serum C-reactive protein (CRP), was done. Results We found a basal FMV of 7.58% and 18.22% after 12 months of treatment, with an improvement of 10.64 points 95% CI (7.58–13.58), p < 0.001. TC decreased from 201.3 ± 58.9 mg/dL to 158.06 ± 50.13 mg/dL (p < 0.01); LDL-C from 125.78 ± 44.4 mg/dL to 78.8 ± 32.9 mg/dL (p < 0.001); HDL-C increased from 49.0 ± 16.8 mg/dL to 52.2 ± 13.8 mg/dL (p = 0.077). The basal and final concentrations of CRP were 4.49 and 2.8, respectively, with a mean decrease of 2.11 mg/dL, 95% CI (0.908–3.32), p < 0.002. Both drugs were well tolerated. Conclusion Ezetimibe plus pravastatin significantly improved FMV in patients with SLE, decreasing ED and the lipid profile. This treatment ameliorated an early process of atherosclerosis and a risk factor for CVD. [ABSTRACT FROM AUTHOR]

Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1–10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti- Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients. [ABSTRACT FROM AUTHOR]

Mortality related to methicillin-resistant Staphylococcus aureus ( MRSA) bloodstream infection ( BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA- BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs ( V- MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex ( CC)5 and carried SCCmec IV and agr2. Microdilution V- MIC50 and V- MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years ( HR 1.88), previous fatal disease ( HR 2.16), Pitt score >1 ( HR 3.45), high-risk source ( HR 1.85) and inappropriate initial treatment ( HR 1.39) as independent predictive factors for mortality. CC5 and CC22 ( HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥1.5 did not have a significant impact on mortality, regardless of the method used to assess it. [ABSTRACT FROM AUTHOR]