Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that preferentially affects the spinal cord and optic nerve. Most patients with NMOSD experience severe relapses that lead to permanent neurologic disability; therefore, limiting frequency and severity of these attacks is the primary goal of disease management. Currently, patients are treated with immunosuppressants. Interleukin-6 (IL-6) is a pleiotropic cytokine that is significantly elevated in the serum and the CSF of patients with NMOSD. IL-6 may have multiple roles in NMOSD pathophysiology by promoting plasmablast survival, stimulating the production of antibodies against aquaporin-4, disrupting blood-brain barrier integrity and functionality, and enhancing proinflammatory T-lymphocyte differentiation and activation. Case series have shown decreased relapse rates following IL-6 receptor (IL-6R) blockade in patients with NMOSD, and 2 recent phase 3 randomized controlled trials confirmed that IL-6R inhibition reduces the risk of relapses in NMOSD. As such, inhibition of IL-6 activity represents a promising emerging therapy for the management of NMOSD manifestations. In this review, we summarize the role of IL-6 in the context of NMOSD.

Relationship between circulating endothelial cells and the predicted risk of cardiovascular events in acute coronary syndromes.

AIMS: The quantification of circulating endothelial cells (CECs) in whole blood is a novel marker of direct endothelial injury and shows promise as a potential biomarker of cardiovascular (CV) risk. The inter-relationship(s) between CECs and predicted CV risk has not been explored in large cohort of 'high-risk' patients. We hypothesized that there would be a significant relationship between increasing CEC counts and predicted CV risk in a broad spectrum of patients presenting with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 197 patients (aged 40-80 years) admitted with a confirmed diagnosis of unstable angina (UA), non-ST-elevation myocardial infarction (MI, NSTEMI), or ST-elevation MI (STEMI). CEC counts were performed on venous whole blood using the immunobead technique. Four well-validated ACS risk scores [(PURSUIT and TIMI for NSTEMI/UA) TIMI (STEMI) and GRACE (all ACS)] were calculated from the initial clinical history and electrocardiogram, as well as from values of laboratory parameters collected within 12 h of admission. We included a healthy control (HC) group of 50 matched patients in order to quantify the accuracy of CEC counts for the diagnosis of ACS and to compare disease vs. HC counts. CEC counts were significantly higher in the disease group when compared with the HC group. CEC counts significantly increased with increasing severity of disease (that is, UA vs. NSTEMI vs. STEMI; P = 0.002). CEC counts were higher among patients with clinical evidence of heart failure (Killip Class II-IV) when compared with those without (Killip Class I) on admission (P < 0.0001). There was a significant correlation between CEC counts and predicted CV risk for each of the four ACS risk scoring schemes (all P < 0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for the entire ACS cohort was 0.82 (95% CI: 0.76-0.88; P < 0.0001). A CEC count of >or=7/mL provided a positive predictive value of 90.6% (95% CI: 85.6-95.7%) and a negative predictive value of 53.5% (41.9-65.1%) for the diagnosis of MI (NSTEMI/STEMI) in the presence of an appropriate clinical presentation. CONCLUSION: There is a significant and positive correlation between increasing CECs and increasing CV risk in ACS. The diagnostic accuracy of CECs in this setting is only 'moderate'. Whilst it is good at confirming the presence of MI, a CEC value of <7.0/mL is less reliable at confidently excluding patients without disease.

Temporal and venepuncture-related decline in circulating endothelial cell capture from mixed venous blood.

BACKGROUND: The quantification of circulating endothelial cells (CECs) in whole blood has evolved as a novel method for the assessment of endothelial function, although major methodological issues remain. We hypothesized that there is a temporal decline in CEC counts in static venesected blood and that venepuncture itself may lead to increased CEC detachment. METHODS: CEC isolation was performed using the immunobead method. For the temporal decline experiment, we included 52 patients presenting with acute coronary syndrome (ACS). We performed CEC counts immediately and at 4 and 24 h later. For the venepuncture decline experiment, we studied 40 patients with stable cardiovascular disease (CVD). CEC counts were determined from the first 4 mL of aspirated venous blood and compared with counts obtained from a subsequent 4 mL sample of blood after at least 7.5 mL of blood had been collected. RESULTS: Among the ACS patients there was a significant temporal decline in CEC counts in static venous blood over a 24 h period (p = 0.013). Among the patients with stable CVD, the median CEC counts obtained from the initial 4 mL of aspirated venous blood were significantly higher (by 32%) than that obtained from the later 4 mL of aspirated venous blood (p = 0.041). CONCLUSIONS: We demonstrated a significant temporal fall in CEC numbers in static venous blood over 24 h following venesection. Furthermore, we have shown that CEC counts are higher in the initial aspirated blood compared with that aspirated from the same needle subsequently. These data would have implications for how CEC determination is undertaken by researchers in studies related to ACS or CVD.