Jana Gottwaldová

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study

Objectives Neutrophil 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). Design Prospective observational cohort study. Setting One university/tertiary centre. Participants A 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. Outcomes Primary 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 methods Using 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). Results The 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%. Conclusions The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

Prognostic Value of Pentraxin-3 Level in Patients with STEMI and Its Relationship with Heart Failure and Markers of Oxidative Stress

Objective. Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). Methods. Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. Results. ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2′-deoxyguanosine, and nitrite/nitrate. Conclusions. Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year.

Determination of asialotransferrin in the cerebrospinal fluid with the HPLC method

Abstract Background: Identification of the content of asialotransferrin in the cerebrospinal fluid is a diagnostic method for childhood-onset ataxia and central nervous system hypomyelination (CACH), also known as vanishing white matter disease (VWM), and also for other types of CNS disorders. Methods: In our work, we have determined the value of the ratio of the asialo form of transferrin to the total transferrin in the CSF using the commercially used VariantTM Bio-Rad system for the determination of carbohydrate-deficient transferrin (CDT) in serum. The peak corresponding to the asialo form of transferrin was identified with electrophoresis with subsequent immunofixation and mass spectrometry (MALDI-TOF/TOF). Results: The intra-assay and inter-assay variations of the asialotransferrin value in CSF were 6.8% and 10.2%, respectively. Analysing CSF samples of 60 subjects (23 men aged 22–68 years and 37 women aged 18–77 years) with normal transferrin values and normal cytology as well as biochemistry parameters in the cerebrospinal fluid, and without apparent signs of neurological disorders, we have found the presence of 25.2 ± 8.2% asialotransferrin. Conclusion: Except for the need to obtain approximately 1.5 mL of cerebrospinal fluid and a tenfold concentrating of the sample, there is no need to conduct any modifications of the preparation procedure for the analytic sample and chromatographic separation normally used for serum samples. The HPLC method of asialotransferrin determination in CSF provides clinically useful results.

Natriuretic peptides, nitrite/nitrate and superoxide dismutase have additional value on top of the GRACE score in prediction of one-year mortality and rehospitalisation for heart failure in STEMI patients — Multiple biomarkers prospective cohort study

BACKGROUND Blood-based biomarkers have a prognostic value in patients with myocardial infarction. The aim of our prospective observational cohort study was to evaluate the prognostic value of biomarkers of different pathophysiological pathways for the occurrence of 1-year all-cause mortality and hospitalisation due to acute heart failure. METHODS AND RESULTS In 593 patients with ST-segment elevation MI (STEMI) treated by primary PCI, biomarkers were evaluated at 24h after MI onset. A minimum of three-year follow-up was achieved in all patients. The combination of 1-year all-cause mortality and hospitalisation due to heart failure was the primary endpoint. A cohort for validation of our combined GRACE-natriuretic peptide (NP) score included 667 STEMI patients. The primary endpoint was reached in 9.3% of patients. Among 21 biomarkers, only B-type natriuretic peptide (BNP), NT-proBNP, superoxide dismutase and nitrite/nitrate, added to clinical GRACE score led to a significant increase in the area under the curve of C statistics, in comparison to GRACE alone (tested by Delongs test). Continuous net reclassification improvement and integrated discrimination index demonstrated an improved reclassification and discrimination of the GRACE model for SOD, BNP and NT-proBNP, and improved reclassification for nitrite/nitrate. Consistent results for this new combined prognostic model GRACE-NP were found also for a validation cohort. CONCLUSIONS The levels of NP have an additional value to the prognostic properties of the GRACE score for the prediction of the combined endpoint of one-year mortality or hospitalisation for AHF. Nitrite/nitrate and SOD are strong prognostic factors, even on top of the GRACE score.

Infectious Complications and Immune/inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study

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.

Interlaboratory study of free monoclonal immunoglobulin light chain quantification

Abstract Background: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. Methods: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. Results: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. Conclusions: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the κ/λ ratio cannot be measured with high precision, κ and λ FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres.

Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?

Abstract Background: The aim of our work was to assess the diagnostic contribution of calprotectin and lactoferrin determinations in the cerebrospinal fluid when distinguishing between bacterial and aseptic meningitides. Methods: In 23 patients with bacterial meningitis (BM) and in 50 patients with aseptic meningitis (AM), we determined the concentrations of calprotectin, lactoferrin and the conventional biomarkers like glucose, total protein, lactate and polynuclear count in the cerebrospinal fluid (CSF). The discriminative power of the various parameters studied was determined by means of receiver operating characteristic (ROC) curves: the area under the curve (AUC), sensitivity, specificity, the positive likelihood ratio (+LR), and the negative likelihood ratio (–LR). Results: The diagnostic efficiency of calprotectin, lactoferrin, lactate, and polynuclear count when distinguishing between bacterial and aseptic meningitides, expressed by ROC curve parameters, was as follows: AUC (0.736, 0.946, 0.932, 0.932), sensitivity (86.2, 96.6, 90.0, 89.7), specificity (58.5, 92.4, 87.0, 90.6), +LR (2.08, 12.8, 6.9, 9.50), –LR (0.24, 0.04, 0.11, 0.11), respectively. The optimal cut point for calprotectin and lactoferrin was 191 ng/mL and 17.8 ng/mL, respectively. Conclusions: Our findings show, that the determination of lactoferrin in the CSF was diagnostically the most efficient marker in distinguishing between bacterial and viral meningitides. Calprotectin was far less efficient diagnostic marker. The polynuclear count and lactate concentration showed a very good diagnostic efficiency as well. The determination of protein and glucose was diagnostically less beneficial.

Unstable angina pectoris prior to ST elevation myocardial infarction in patients treated with primary percutaneous coronary intervention has no influence on prognosis.

BACKGROUND Pre-infarction unstable angina pectoris (UAP) can be considered ischemic preconditioning. The aim of this study was to compare short and long term outcomes in patients with or without pre-infarction UAP and ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS 593 patients with STEMI (388 without and 205 with UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin, endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were assessed. Echocardiography was undertaken on the fourth day after MI and after 12 months. The median follow-up was 37 months. RESULTS We found no significant differences in sex, age or risk factors for atherosclerosis between the UAP and non-UAP group. As the median time from the onset of chest pain to admission was significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a propensity score to obtain comparable matched groups for use in further analyses. The levels of NT-proBNP were significantly higher on admission and after 24 hours in the UAP group. Left ventricular functions according to invasive and echocardiographic parameters were entirely comparable at hospitalization and after 12 months. No differences were found in severity index of acute heart failure during hospitalization. The incidence of major acute coronary events during follow-up was comparable for the groups. CONCLUSIONS In patients with STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical effect during hospitalization or during long-term follow-up.

Efficient use of basic biochemical methods to prove the presence of monoclonal protein in the clinical diagnosis of malignant monoclonal gammopathy.

Background: This retrospective study evaluates the diagnostic sensitivity of biochemistry methods for the clinical diagnosis of malignant monoclonal gammopathy. In patients with renal insufficiency, renal reference interval as well as standard reference interval is used for evaluating the ratio of free light chains. Methods: We examined samples in 281 patients who were diagnosed with malignant monoclonal gammopathy. The samples were taken at baseline, prior to treatment. Serum and urine protein electrophoresis, serum and urine immunofixation electrophoresis (SIFE+UIFE) and levels of free light chains in serum (FLC) were investigated. Results: Combination of methods with the highest diagnostic sensitivity is the use of maximal number of tests (SIFE+ UIFE + FLC), which identified 98.6% of patients. The achieved results do not statistically significantly differ from the procedure recommended by the International Myeloma Working Group (IMWG) which omitts the urine testing (SIFE + FLC) and identifies 97.9 % of patients (p = 0.523). By using the renal reference ratio of free light chains in patients with renal insufficiency the number of patients identified decreased to the border of significance (p = 0.06) but the number of patients identified by the combination with serum immunofixation (SIFE + FLC) remained the same. Conclusions: The testing algorithm recommended by IMWG for screening patients with the diagnosis of monoclonal gammopathy is effective, diagnostic sensitivity is not significantly lower than the maximal available. Using the renal reference ratio of FLC for evaluation in combination with immunofixation in the serum does not reduce the diagnostic sensitivity of the test and has been reported to increase specificity.

Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage

Background Subarachnoid hemorrhage (SAH) is a severe condition associated with high mortality. Early brain injury (EBI) plays an important role in the pathophysiology of SAH, and inflammation is a major contributor to EBI. Inflammation is a widely studied topic in both experimental and clinical conditions; however, just a few clinical studies have focused primarily on the early inflammatory response after SAH, and detailed information about the association between the dynamics of early inflammatory response with main clinical characteristics is lacking. This study analyzes the early dynamics of inflammatory response after SAH and evaluates the possible associations between the markers of early inflammatory response and main clinical characteristics. Patients and Methods A total of 47 patients with a diagnosis of aneurysmal SAH within the last 24 hours were enrolled in the study. All treatments, including treatment of aneurysm (surgery/coiling) and implantation of a drainage system (external ventricular drainage/lumbar catheter), were conducted in the same way as in other patients with this diagnosis. Blood and cerebrospinal fluid (CSF) samples were collected three times a day for 4 days. The dynamics of proinflammatory cytokines were assessed, and associations between levels of the proinflammatory cytokines interleukin (IL)‐6, IL‐1&bgr;, or tumor necrosis factor (TNF)&agr; and main clinical characteristics were evaluated using linear mixed‐effect models. Results The CSF levels of IL‐6 were massively increased initially after SAH (up to 72 hours) with an additional increase in later phases (after 72 hours), but there was high variability in IL‐6 levels. A significant association was noted between the Glasgow Outcome Scale score and both overall levels of IL‐6 (p = 0.0095) and their dynamics (p = 0.0208); the effect of the Hunt and Hess scale was borderline (p = 0.0887). No association was found between IL‐6 levels and Fisher grade, modality of treatment (surgery, coiling, no treatment), and later development of cerebral vasospasm. Plasmatic levels of IL‐6 increased slightly, but no significant association was found. The levels of IL‐1&bgr; and TNF&agr; were within the physiologic range in both CSF and plasma. Conclusions Early dynamics of IL‐6 in CSF are associated with a patienSymbols outcome. But it is difficult to use IL‐6 alone for outcome prediction due to its high variability. The question is whether the dynamics of IL‐6 could be used in combination with other early markers associated with brain injury. More detailed research is required to answer this question. Symbol. No caption available.