CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis

BACKGROUND: The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. METHODS AND RESULTS: Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. CONCLUSIONS: Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies

Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: A multi-centre all-case analysis

Aims Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine. Methods and results One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among mate patients after colchicine treatment (36 vs. 17%, P = 0.046), and those with previous corticosteroid treatment (43 vs. 13%, P = 0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% Cl: 1.65-27.02) and mate gender (OR 4.20, 95% Cl: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy. Conclusion Treatment with colchicine is highly effective in preventing recurrent pericarditis, white pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis

Indirect calibration between clinical observers - application to the New York Heart Association functional classification system

<p>Abstract</p> <p>Background</p> <p>Previous studies showed an inter-observer agreement for the NYHA classification of approximately 55%. The aim of this study was to calibrate the New York Heart Association (NYHA) classification system between observers, increasing its reliability.</p> <p>Results</p> <p>Among 1136 community-dwellers in Porto, Portugal, aged ≥ 45 years, 265 reporting breathlessness answered a 4-item questionnaire to characterize symptom severity. The questionnaire was administered by 7 physicians who also classified the subject's functional capacity according to NYHA. Each subject was assessed by one physician. We calibrated NYHA classifications by the concurrent method, using 1-parameter logistic graded response model. Discrepancies between observers were assessed by differences in ability thresholds between NYHA classes I-II and II-III. The ability estimated by the model was used to predict the NYHA classification for each observer.</p> <p>Estimates of the first and second thresholds for each observer ranged from -1.92 to 0.46 and from 1.42 to 2.30, respectively. The agreement between estimated ability and the observers' NYHA classification was 88% (kappa = 0.61).</p> <p>Conclusions</p> <p>The study objectively indicates the main reason why several studies have reported low inter-observer is the existence of discrepant thresholds between observers in the definition of NYHA classes. The concurrent method can be used to minimize the reliability problem of NYHA classification.</p

Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH. METHODS AND RESULTS: In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH. CONCLUSIONS: Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation

The efficacy of colchicine in the treatment of recurrent pericarditis related to postcardiac injury (postpericardiotomy and postinfarcted) syndrome: A multicenter analysis

Background: Pericarditis related to the postcardiac injury syndrome (PCIS) following myocardial infarction or cardiac surgery is a troublesome and often recurrent clinical entity resistant to therapeutic interventions. The usefulness of colchicine in the prevention of recurrent PCIS has not been evaluated. Objective: We performed a cumulative analysis of available multicenter data with the aim of evaluating the efficacy of colchicine in the treatment of recurrent PCIS. Methods and Results: The study was designed as a multicenter all-cases analysis. Researchers who had published studies and case reports on colchicine treatment in recurrent pericarditis related to PCIS during the last 15 years were approached and asked to contribute all available cases to the database. There were 28 patients, 18 male (64%) and 10 female (36%), ranging in age from 21 to 82 years (mean 53 \ub1 15 years). PCIS pericarditis was secondary to pericardiotomy in 19 patients and infarction in 9. In 21 patients (75%), colchicine therapy was discontinued during follow-up and renewed only in the case of relapse. In these patients, the total period of treatment was summed up for analysis. 7 patients (25%) were taking colchicine as a permanent treatment, and no colchicine-free follow-up was documented. In total, 130 recurrences (mean 4.64 \ub1 3.7 per patient, range 2-16) were noted before colchicine therapy was initiated. During colchicine treatment (mean duration of treatment 16.6 \ub1 13.5 months), a significant reduction in the number of recurrences was observed. Only 5 of 28 patients (18%) presented with new recurrences (mean 0.25 \ub1 0.59 vs. 4.64 \ub1 3.7 per patient in the precolchicine period, p < 0.001). The mean follow-up period after colchicine discontinuation (data were available for 21 patients) was 31.9 \ub1 28 months; during follow-up, 13 patients (62%) remained recurrence free and 8 of them (38%) experienced relapses (mean 0.43 \ub1 0.6 per patient, p < 0.001 vs. precolchicine). Conclusions: It seems that colchicine may be effective in preventing new relapses in patients with recurrent pericarditis related to postcardiac injury both during active therapy and after its discontinuation