Rheumatoid arthritis (RA) is a model of multigenic inflammatory disorder in which tumor necrosis factor-alpha (TNF-alpha) plays an important role. Genetic factors may be implicated in the susceptibility to disease initiation as well as in severity of disease course. Elevated levels of TNF-alpha in the plasma and synovial fluid from RA patients may be associated with polymorphisms in the promoter region of the TNF-alpha gene. The aim of this study was to elucidate putative association between the -308 G/A polymorphism in the promoter region of the TNF-alpha gene and susceptibility to onset and severity of RA. A total of 130 RA patients and a control group of 150 healthy subjects with similar age and sex distribution were available for the study. All patients fulfilled the American College of Rheumatology revised criteria for RA. RA patients had a disease duration of at least 2 years. Radiographs of both hands of all RA patients were scored with the Steinbrocker method. There were 15 patients of stage I (nonerosive form) of RA and 114 patients of stages II-IV (erosive form). To assess the RA patient's functional ability, the Health Assessment Questionnaire (HAQ) was used. The -308 G/A promoter polymorphism of the TNF-alpha gene was detected by polymerase chain reaction and restriction fragment length polymorphism analysis. No differences in genotype distribution and allelic frequences of -308 G/A TNF-alpha promoter polymorphism have been found between RA patients and the control group. Significant differences have been observed within the RA group divided according to the radiographic progression of disease based on the Steinbrocker radiographic score and functional ability (HAQ). These results suggest an association of the -308 G/A polymorphism of the TNF-alpha gene with the severity of RA.

ObjectivesNeutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP).DesignProspective observational cohort study.SettingOne university/tertiary centre.ParticipantsA total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission.OutcomesPrimary outcome: 1-year mortality. Secondary outcomes: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure.Statistical methodsUsing the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI).ResultsThe NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%.ConclusionsThe measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

BackgroundAccording to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients’ comorbidities, NYHA and NT-proBNP levels.Methods and resultsA total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40–49%) were enrolled consecutively. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (EP). The occurrence of EP was 14.9% and grew with higher NYHA, namely 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III–IV) (p<0.001). The occurrence of EP was 3%, 10% and 15–37% in patients with NT-proBNP levels ≤125 ng/L, 126–1000 ng/L and >1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p<0.001) and AUC 0.722 (p<0.001) respectively. The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and being on a higher dose of furosemide (>40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790).ConclusionThe use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation.

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Our findings suggest that polymorphisms in the MMP-2 gene promoter do not contribute significantly to the interindividual periodontitis susceptibility and/or severity in European Caucasians, and they are not regulatory variants in this disease.