NGAL (neutrophil gelatinase-associated lipocalin) is an acute phase protein, participating in antibacterial immunity. NGAL forms a complex with metalloproteinase 9 (MMP-9), thereby increasing its activity and preventing its degradation. NGAL is freely filtered through the glomerular membrane and reabsorbed by endocytosis in the proximal tubule. NGAL detected in urine is produced mainly in the distal nephron. Elevated serum and urine NGAL allows diagnosis of acute kidney injury approximately 24 hours earlier than plasma creatinine concentration. Increased levels of NGAL were detected in patients with acute myocardial infarction, heart failure or stroke and were demonstrated to be strong predictors of adverse prognosis.

Introduction:Patients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers.Methods:Eighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock.Results:Infection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875.Conclusion:The prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections did not prolong statistically significantly the duration of mechanical ventilation and did not increase the prevalence of hospital mortality in this high-risk CS population. CS due to acute myocardial infarction was accompanied by a strong and highly variable inflammatory response, but it did not reach the intensity of the inflammatory response observed in patients with septic shock. An extensive immune/inflammatory response in patients with CS is linked to a poor prognosis.

Accurate evaluation of the appearance of QTc sex differences during childhood and adolescence is intricate. Inter-subject differences of individual QT/RR patterns make generic heart rate corrections inaccurate because of fast resting heart rates in children. The study investigated 527 healthy children and adolescents aged 4–19 years (268 females, 50.9%). All underwent continuous ECG 12-lead monitoring while performing postural changes during a 70-min investigative protocol to obtain QT interval measurements at different heart rates. On average, more than 1200 ECG measurements (QT interval and its 5-min history of preceding RR intervals) were made in each subject. Curvilinear QT/RR regression involving intra-individual correction for QT/RR hysteresis were calculated in each subject. The projection of the QT/RR regressions to the heart rate of 60 beats per minute defined individually corrected QTc intervals. In males, gradual QTc shortening by about 15 ms appeared during the ages of 13–19 years synchronously with the incidence of secondary sex signs ( p = 0.016). On the contrary, whilst gradual QTc prolongation by about 10 ms appeared in females, it occurred only during ages 16–19 years and was not related to the incidence of secondary sex signs ( p = 0.18). The study also showed that in children and adolescents, linear QT/RR models fit the intra-subject data significantly more closely than the log-linear models ( p < 0.001). The study speculates that hormonal shifts during puberty might be directly responsible for the QTc shortening in males but that QTc prolongation in females is likely more complex since it was noted to follow the appearance of secondary sex signs only after a considerable delay.

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.

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2′-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker’s ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin.

Background/Aims: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients. Methods: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model. Results: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1–20.6) for AKI. Conclusion: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

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Limited evidence suggests that specificity of cardiac troponin T (cTnT), a highly sensitive biomarker of myocardial injury, is reduced in patients with skeletal myopathies. Whether amyotrophic lateral sclerosis (ALS)-the most common motor neuron disease-could be also associated with abnormal plasma or serum cTnT levels remains unclear. Our objective was to assess cTnT levels in patients with ALS without known cTnT elevating conditions. Among ALS patients seen at our institution until 2012 we identified those who had their cTnT measured. Patients who suffered from conditions known to elevate cTnT were excluded. A case-control analysis comparing cTnT levels of these ALS patients to matched non-ALS controls fulfilling the same inclusion criteria was performed. We included 40 ALS patients of whom 27 (68 %) patients had a positive cTnT. In the control group (n = 40), 2 (5 %) tested as cTnT positive (p < 0.001). Among the ALS patients who underwent cTnT evaluation on more occasions (n = 7; median follow-up = 1.08 years), 2 (29 %) patients tested positive during the initial measurement while 6 (86 %) of them had positive cTnT at the subsequent evaluations. ALS patients with increased cTnT had been diagnosed with ALS significantly earlier than those without the elevation. Our findings raise the possibility that ALS may cause cTnT elevations. Further studies are needed to confirm these findings, clarify the pathophysiological mechanism, and establish the significance of cTnT elevations in patients with ALS.