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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.

ObjectivesThe aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE).BackgroundThere is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available.MethodsThe multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0%) allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29), or SAVR with the Edwards Perimount bioprosthesis (n = 13). Standardized endpoints were prospectively followed during the 12-month follow-up.ResultsThe clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis) = 0.872 for TAVI group, resp. 0.765 (p<0.05) for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1), ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750–0.948; p<0.05 for all). The addition of MDA to a currently used clinical model (EuroSCORE) significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0–365 days) by the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) (p<0.05).Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up.ConclusionWe identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical “TAVIscore” would be highly appreciated. Such dedicated scoring system would enable further testing of adjunctive value of various biomarkers.

Targeting cholinergic anti-inflammatory pathway is a promising way of immunomodulation which attenuates inflammation in a complex manner without causing immunosuppression.

The main objective was to evaluate, whether the subarachnoid hemorrhage (SAH)-associated early inflammatory response has focal or global character, i.e., whether areas distant to hematoma may be affected by an early inflammatory response. The second objective was to evaluate the association of anesthesia recovery time for basic reflexes/neurological functions with severity of SAH. SAH was induced in rats using an endovascular perforation model. Anesthesia recovery time was evaluated for pain reaction recovery time (spinal level), spontaneous ventilation recovery time (brain stem level), and consciousness recovery time (neocortical level). mRNA expressions of TNFα, IL-1β, IL-6, ICAM-1, and VCAM-1 in areas adjacent and distant to hematoma were evaluated between 2 and 8 h after SAH. Serum levels of TNFα, IL-1β, and IL-6 were assessed at 4 and 8 h after SAH. Anesthesia recovery time of all selected parameters was associated with severity of SAH. The consciousness recovery time test had the best predictive value, while the spontaneous ventilation recovery time test was able to bring information in the shortest time. The mRNA expressions of pro-inflammatory cytokines were significantly increased in severe SAH groups in both adjacent and distant areas. The inflammatory response in mild/moderate SAH groups was less strong, peaking at 4 h after SAH. Serum levels of pro-inflammatory cytokines were ambiguous. Anesthesia recovery time may be useful for bleeding severity prediction in the SAH model; however, further validation is needed. Severe subarachnoid hemorrhage is associated with the strong early inflammatory response, which has a global character, while mild subarachnoid hemorrhage is accompanied by a weaker inflammation.