Prevalence,clinical correlates and treatment of permanent atrial fibrillation among the elderly: insights from the first prospective population-based study in rural Greece

To investigate the prevalence of permanent atrial fibrillation (AF), its clinical associated conditions and treatment status in the elderly population in rural Greece. 720 people (46.1% males) older than 65 years (mean age: 72.5 ± 5.7 years) living in four villages in rural Greece were screened with an electrocardiogram (response rate: 90.5%) for the presence of permanent AF. They underwent a physical examination, including blood pressure (BP) measurement, and body mass index (BMI) calculation, in addition to an interview about their medical history, physical activity, smoking habits, alcohol consumption and medication use. Subjects with AF for whom anticoagulants were contraindicated were identified and stroke risk stratification was performed using the CHADS2 algorithm. The prevalence of permanent AF was 5% (6.6% among men and 3.6% among women) and it increased with age. In the entire population, ECG evidence of myocardial ischaemia and ventricular premature beats were independently associated with the presence of permanent AF (OR 5.266; 95% CI 2.22–12.49, P = 0.0001 and OR 2.61; 95% CI 1.059–6.432, P = 0.037, respectively), while female sex was independently associated with the absence of the AF (OR 0.327; CI 0.147–0.729, P = 0.006). From those patients who were eligible for anticoagulation, 40.6% were treated with anticoagulants, 34.3% were given antiplatelets therapy and the rest received no antithrombotic treatment. This is the first prospective study demonstrating the prevalence, clinical correlates and treatment status of permanent AF in Greece. These results confirm the high prevalence of permanent AF among the elderly and underscore the issue regarding anticoagulants underutilization.     

Diabetes mellitus and coronary revascularization procedures

Revascularization strategy for coronary artery disease in diabetic patients remains a field of controversy. Percutaneous coronary intervention has a less favourable outcome in these patients, though drug eluting stents have significantly improved the outcome. Although in most series, the outcome with coronary artery bypass grafting is worse in diabetic populations, surgery seems to be superior to angioplasty, particularly in diabetics with multivessel disease. Results from randomized trials such as the ongoing FREEDOM, CARDia and SYNTAX may define the role of each procedure in the treatment of diabetic patients with coronary artery disease.     

Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model

OBJECTIVE: Despite advances in autologous stem cell transplantation and chemotherapy, multiple myeloma (MM) remains an incurable disease. Due to the role of natural killer (NK) cells in host resistance against several tumors, it is of interest to explore the anti-MM activity of NK cells. For this reason, we aimed to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2) administration, and if ex vivo activated and intravenously administered NK cells prolong survival in MM-bearing C57BL/KaLwRij mice. METHODS: The anti-MM effect of IL-2 was tested by intraperitoneal injection into the 5T33MM-inoculated mice. Subsequently, in vivo effector cell depletions were performed by administration of anti-NK1.1 or anti-CD8 monoclonal antibodies. Finally, magnetically separated and activated NK cells from splenocytes of C57BL/KaLwRij mice were adoptively transferred to tumor-bearing mice in conjunction with IL-2 treatment. RESULTS: IL-2 administration into MM-bearing mice significantly prolonged their survival. This effect was diminished by in vivo depletion of NK cells. Adoptive transfer of activated NK cells showed a significant in vivo anti-MM effect that was dependent on cell dose. Biodistribution of the marked adoptively transferred NK cells correlated with MM cells' homing sites. CONCLUSION: These data suggest that activated NK cells have a promising potential in adoptive immunotherapy for MM.     

The incremental effect of obstructive sleep apnoea syndrome on arterial stiffness in newly diagnosed essential hypertensive subjects

OBJECTIVE: Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness. METHODS: Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I-II essential hypertension suffering from OSAS (35 men, aged 49 +/- 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid-femoral pulse wave velocity (c-fPWV) measurements. RESULTS: Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI)>or =5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 +/- 4 versus 29.3 +/- 4 kg/m2, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 +/- 0.06 versus 0.42 +/- 0.07, P=0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c-fPWV by 9% (8.56 +/- 0.49 versus 7.85 +/- 0.93 m/s, P=0.001) and this difference remained significant even after adjustment for confounders (P=0.04). In the total study population, c-fPWV was correlated with age (r=0.35, P=0.015), office systolic blood pressure (r=0.30, P=0.007), RWT (r=0.30, P=0.03), logAHI (r=0.389, P=0.0001) and minimum oxygen saturation (r=-0.418, P=0.0001). CONCLUSIONS: OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk.     

XbaI GLUT1 Gene Polymorphism and the Risk of Type 2 Diabetes with Nephropathy

Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1) contributes to development of microangiopathy in diabetes mellitus type 2 (DM) patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN). Study population (n = 240) consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN)), and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h) and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(−) carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR) 2.08 [95% confidence interval (1.14–3.79)]. However, there was no evidence of association between XbaI(−) and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55–2.26). Thus, the GLUT1 XbaI(−) allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN.     

Relationship between the type I interferon signature and the response to rituximab in rheumatoid arthritis patients

Objective

To analyze the relationship between the type I interferon (IFN) signature and clinical response to rituximab in rheumatoid arthritis (RA) patients.

Methods

Twenty RA patients were treated with rituximab (cohort 1). Clinical response was defined as a decrease in the Disease Activity Score evaluated in 28 joints (DAS28) and as a response according to the European League Against Rheumatism (EULAR) criteria at week 12 and week 24. The presence of an IFN signature was analyzed in peripheral blood mononuclear cells by measuring the expression levels of 3 IFN response genes by quantitative polymerase chain reaction analysis. After comparison with the findings in healthy controls, patients were classified as having an IFN high or an IFN low signature. The data were confirmed in a second independent cohort (n = 31). Serum IFNα bioactivity was analyzed using a reporter assay.

Results

In cohort 1, there was a better clinical response to rituximab in the IFN low signature group. Consistent with these findings, patients with an IFN low signature had a significantly greater reduction in the DAS28 and more often achieved a EULAR response at weeks 12 and 24 as compared with the patients with an IFN high signature in cohort 2 versus cohort 1. The pooled data showed a significantly stronger decrease in the DAS28 in IFN low signature patients at weeks 12 and 24 as compared with the IFN high signature group and a more frequent EULAR response at week 12. Accordingly, serum IFNα bioactivity at baseline was inversely associated with the clinical response, although this result did not reach statistical significance.

Conclusion

The type I IFN signature negatively predicts the clinical response to rituximab treatment in patients with RA. This finding supports the notion that IFN signaling plays a role in the immunopathology of RA.

     

Neuroleptic malignant syndrome without fever after addition of oxcarbazepine to long-term treatment with amisulpride

OBJECTIVE: Our goal was to report a case of malignant neuroleptic syndrome in a patient administered with both oxcarbazepine (OXCBZ) and amisulpride (AM). METHOD: We present a case of a young man who presented with symptoms of malignant neuroleptic syndrome after progressive titration of OXCBZ (1200 mg) added to the long-term treatment with AM (800 mg). RESULTS: After discontinuation of AM and administration of dopaminergic drugs, his clinical symptoms improved gradually. CONCLUSION: This case suggests that clinicians should consider the risk of neuroleptic malignant syndrome when OXCBZ is coadministered to patients undergoing long-term treatment with neuroleptics.