Nebojsa Radovanovic

Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer.

Colorectal cancer is one of the leading causes of cancer related death in developed countries. One of the reasons is the absence of tumor specific diagnostic and prognostic markers. The aim of this study was to examine the correlation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expressions in serum and clinicopathological features of the colorectal adenocarcinoma. Another aim was to examine expression of MMP-9 in the tissue of the colorectal carcinoma in MMP-9 serum positive patients. In addition, we tried to establish the correlation between preoperative levels of serum markers (CEA and CA 19-9) and presence of MMP-2 or MMP-9. The study was performed on 32 patients with colorectal adenocarcinoma who underwent surgery and 11 patients in a control group who were operated for benign diseases. The samples were analyzed by SDS-PAGE to determine the molecular mass and SDS-PAGE zymography to determine levels of MMP-2 and MMP-9. Expression of MMP-9 was determined immunohistochemically in the tissue of the colorectal carcinoma of MMP-9 serum positive patients. MMP-2 and MMP-9 levels were increased in the serum of the patients with colorectal cancer compared to the control group. There was significant correlation in MMPs levels among the patients with tumor stage I and II and the patients with tumor stage III and IV. Obtained results did not demonstrate correlation between levels of CEA, CA 19-9 and presence of MMP-2 or MMP-9. MMP-9 expression was positive in 85% of MMP-9 serum positive patients with colorectal carcinoma. The overexpression of MMP-2 and MMP-9 strongly suggests its association with colorectal adenocarcinoma. Detection of MMP-2 and MMP-9 in serum might be useful for identification of patients with higher risk for colorectal cancer recurrence.

Glycogen phosphorylase BB in myocardial infarction

Early experimental and clinical reports on glycogen phosphorylase BB (GPBB) kinetics following myocardial ischemic injury suggested that it could be a useful diagnostic marker for early detection of acute myocardial infarction (AMI). After more than two decades of investigation, there is now overwhelming body of evidence that do not support the use of GPBB measurement in diagnosis of acute AMI in patients presenting with acute chest pain. Currently, GPBB cannot be recommended as a diagnostic marker of AMI either as a stand-alone test or as an addition to (high-sensitive) troponin testing. It should be noted that these considerations apply to the early diagnosis of AMI, not to the prognostic stratification, which is also suggested but it warrants further investigation. The aim of this review is to summarize available evidence of GPBB measurement in early diagnosis of myocardial infarction.

The Timing of Infarction Pain in Patients with Acute Myocardial Infarction after Previous Revascularization

Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.

In-Hospital and Long-Term Prognosis after Myocardial Infarction in Patients with Prior Coronary Artery Bypass Surgery; 19-Year Experience

To present a 19-year experience of the prognosis of patients with acute myocardial infarction (AMI) and prior coronary artery bypass surgery (CABS), 748 patients with AMI after prior CABS (postbypass group) and a control group of 1080 patients with AMI, but without prior CABS, were analyzed. All indexes of infarct size were lower in the postbypass group. There was more ventricular fibrillation in the postbypass group. In-hospital mortality was similar (p = 0.3675). In the follow-up period, postbypass patients had more heart failure, recurrent CABS, reinfarction, and unstable angina than did control patients. Cumulative survival was better in the control group than in the postbypass group (p = 0.0403). Multiple logistic regression model showed that previous angina (p = 0.0005), diabetes (p = 0.0058), and age (p = 0.0102) were independent predictor factors for survival. Use of digitalis and diuretics, together with previous angina, also influenced survival (p = 0.0092), as well as male gender, older patients, and diabetes together (p = 0.0420). Patients with AMI after prior CABS had smaller infarct, but more reinfarction, reoperation, heart failure, and angina. Previous angina, diabetes, and age, independently, as well as use of digitalis and diuretics together with angina, and male gender, older patients, and diabetes together, influenced a worse survival rate in these patients.

Practical Aspects of Monitoring of Antiplatelet Therapy.

&NA; Despite the application of new antiplatelet drugs (prasugrel and ticagrelor), dual antiplatelet therapy with clopidogrel and aspirin remains the standard for patients with acute coronary syndrome undergoing percutaneous coronary intervention, especially in countries of low socioeconomic status. Regardless of the proven benefits, numerous studies have shown that certain groups of patients who receive standard doses of clopidogrel and aspirin do not respond adequately, and many of them also exhibit adverse cardiovascular events. Studies have shown that the risk of stent thrombosis and ischemic complications is higher in patients with: acute coronary syndrome, diabetes mellitus, thrombocytosis, reduced systolic function of the left ventricle with ejection fraction less than 30%, presence of multiple stents, longer and thinner stents, and renal failure. In these patients it is particularly important to assess the response to clopidogrel and selecting adequate antiplatelet therapy; this provides an impetus for platelet function tests. The second especially significant group to target for laboratory evaluation includes patients with increased risk of bleeding, such as elderly patients, patients with low body weight, anemia, thrombocytopenia, renal failure, past or current ventricular or duodenal ulcer, coagulopathy, or liver disease. The third important application of platelet function tests entails the preparation and evaluation of the time for surgical interventions or invasive diagnostic procedures in patients on antiplatelet therapy. These tests can also be helpful for monitoring the effects of therapy of bleeding due to platelet dysfunction. For high‐risk patients the careful selection of optimal antiplatelet drug(s) on the basis of estimated individual risk of thrombosis and bleeding, pharmacodynamic characteristics of each drug, and patiens comorbidity remains essential.

Usefulness of NT-proBNP in the Follow-Up of Patients after Myocardial Infarction

Summary Background: Since serial analyses of NT-proBNP in patients with acute coronary syndromes have shown that levels measured during a chronic, later phase are a better predictor of prognosis and indicator of left ventricular function than the levels measured during an acute phase, we sought to assess the association of NT-proBNP, measured 6 months after acute myocardial infarction (AMI), with traditional risk factors, characteristics of in-hospital and early postinfarction course, as well as its prognostic value and optimal cut-points in the ensuing 1-year follow-up. Methods: Fasting venous blood samples were drawn from 100 ambulatory patients and NT-proBNP concentrations in lithium-heparin plasma were determined using a one-step enzyme immunoassay based on the »sandwich« principle on a Dimension RxL clinical chemistry system (DADE Behring-Siemens). Patients were followed-up for the next 1 year, for the occurrence of new cardiac events. Results: Median (IQR) level of NT-proBNP was 521 (335–1095) pg/mL. Highest values were mostly associated with cardiac events during the first 6 months after AMI. Negative association with reperfusion therapy for index infarction confirmed its long-term beneficial effect. In the next one-year follow-up of stable patients, multivariate Cox regression analysis revealed the independent prognostic value of NT-proBNP for new-onset heart failure prediction (p=0.014), as well as for new coronary events prediction (p=0.035). Calculation of the AUCs revealed the optimal NT-proBNP cut-points of 800 pg/mL and 516 pg/mL, respectively. Conclusions: NT-proBNP values 6 months after AMI are mainly associated with the characteristics of early infarction and postinfarction course and can predict new cardiac events in the next one-year follow-up.

Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer

AIM To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer. METHODS Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocarcinoma suspected of local recurrence and metastatic disease. The results were compared with conventional diagnostics. RESULTS Immunoscintigraphic investigation was done in 53 patients. Tumor recurrence occurred in 38 patients, and was confirmed by other diagnostic modalities in 35. In 15 patients, immunoscintigraphic findings were negative, and confirmed in 14 with other diagnostic methods. Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen. Statistical analysis of parameters of radiopharmaceutical groups imacis, indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals. The analysis of immunoscintigraphic target focus was clearly improved using tomography. CONCLUSION Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.

Gallbladder motility disorders estimated by non-invasive methods.

BACKGROUND/AIMS The aim is to compare the radionuclide (DC) and ultrasonographic (US) method in the assessment of gallbladder (GB) motility. METHODOLOGY The study was performed in 15 controls (C), 10 patients with acute cholecystitis (AC), 20 patients with chronic acalculous cholecystitis (CAC), 26 patients with chronic cholecystitis with calculosis (CCC) as well as in 15 patients with GB dyskinesia (D). GB emptying period (EP), ejection fraction (EF) and ejection rate (ER) were estimated with dynamic cholescintigraphy (DC) and US. RESULTS The DC and US finding in the patients with AC was typical in all the patients, i.e. GB was not visualized at all on DC, while on US, stone was visible in the cystic duct. There were significant differences (p<0.05) between the EF and ER values obtained between C and the three groups of patients CAC, CCC and D, using both methods. However, there were no significant differences in EF, EP and ER values among CAC, CCC and D (p>0.05). There was also high correlation between the results obtained with both methods in all the groups of patients studied. CONCLUSIONS The results obtained by both methods are valuable for the assessment of GB motility. Although there are no significant differences and there is a high correlation between the values, radionuclide method is more precise, because it can register motility continuously.

B-type natriuretic peptide in outpatients after myocardial infarction: Optimized cut-off value for incident heart failure prediction

Higher levels of natriuretic peptides were identified in outpatients after myocardial infarction (MI) compared to the healthy population, even in the absence of heart failure (HF). Therefore, we assessed the optimal cut-off value of B-type natriuretic peptide (BNP) in relation to new-onset HF prediction in 79 post-MI patients with preserved left ventricular systolic function (ejection fraction >40%). Plasma BNP was measured by enzyme immunoassay, 6 months after MI and patients were followed-up for the next one year. Cox proportional regression model analysis revealed the independent prognostic value of BNP for HF prediction (p=0.005). As assessed by ROC analysis the optimal cut-off value of BNP was 175 pg/mL (sensitivity 82%; specificity 77%, AUC 0.77), associated with significantly different rates of incident HF by Kaplan-Meier analysis (p=0.001). In this population of outpatients with preserved left ventricular systolic function after MI, BNP strongly correlated with new-onset HF development at the optimal cut-off value of 175 pg/mL.

Sex and age differences and outcomes in acute coronary syndromes

BACKGROUND There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). METHODS From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.