Reference intervals of 24 trace elements in blood, plasma and erythrocytes for the Slovenian adult population.

OBJECTIVES: The aim of the present study was to establish the population- and laboratory-specific reference intervals (RIs) for the Slovenian adult population for 24 trace elements (TEs) in blood, plasma and erythrocytes and to evaluate the impact of gender, age, seafood consumption, smoking habits and amalgam fillings on TEs levels. METHODS: TEs (Mn, Co, Cu, Zn, Se and Mo, Li, Be, V, Cr, Ni, Ga, As, Rb, Sr, Ag, Cd, Sn, Cs, Au, Hg, Tl, Pb and U) were determined in 192 a priori selected blood donors (107 women and 85 men, aged 18-65 years), using inductively coupled plasma mass spectrometry (ICP-MS) with the Octopole Reaction System. Participants filled out a questionnaire, and RIs were established according to the Clinical and Laboratory Standards Institute (CLSI) guidelines for TEs. RESULTS: Uniform RIs for non-essential and gender-specific for essential TEs in blood, plasma and erythrocytes were established. In our population, higher blood and plasma Cu, and erythrocyte Mn levels in women were found. In men, blood Zn, plasma Zn, Mn and Se, and erythrocyte Cu levels were higher. Zn levels were higher in 30-39 years age group. Pb and Sr increased with age. Smoking positively affected Cd, Pb, Cs and Rb; seafood consumption increased As, Hg and Zn; and amalgam increased Hg, Ag and Cu levels. CONCLUSIONS: Essential TEs were inside recommended levels, and the non-essential ones were far below critical levels. Established RIs will provide an important foundation for clinical diagnostics, safety erythrocyte transfusions assessment, toxicology and epidemiological studies.

Verification and Comparison of Qualitative Serological Assays for Anti-SARS-COV-2 IgM and IgG Antibodies Detection.

Background: Due to their wide application in the SARS-CoV-2 pandemic, we verified and compared three qualitative serological methods in order to select the most optimal that will best serve its purpose under laboratory conditions. Methods: We assessed the diagnostic characteristics of two automated serological methods (Roche Elecsys® Anti-SARS-CoV-2 and Abbott SARS-CoV-2 IgG) and a POCT test (Colloidal Gold Method SARS-CoV-2 IgM/IgG Antibody Assay Kit). In the process of verification, analytical precision was also assessed for the automated assays. Results: Diagnostic characteristics were determined by measuring antibodies against SARS-CoV-2 in 91 RT-PCR-negative and 60 RT-PCR-positive samples. The POCT test gave the highest number of false positive cases (8.61%). Roche Elecsys® Anti-SARS-CoV-2 gave only 2.65% false positivity and showed the highest diagnostic sensitivity of 98.33% (95% CI: 91.06-99.96), while Abbott SARS-CoV-2 IgG method showed 100.00% (95% CI: 96.03-100.00) diagnostic specificity and an almost perfect agreement with Roche Elecsys® Anti-SARS-CoV-2. When assessing the precision of the automated methods, we observed some variability in the positive control samples, but the values did not affect clinical interpretation. Conclusion: Both automated methods demonstrate superior diagnostic characteristics compared to the Colloidal Gold Method, and this POCT test is not considered as an appropriate choice for routine testing. The two automated methods showed low variability without altering the results and their interpretation.

Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function.

We have recently shown that minor subclinical creatinine dynamic changes enable the excellent detection of acute kidney injury (AKI) within 6-12 h after cardiac surgery. The aim of the present study was to examine a combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine were determined after the induction of general anesthesia, at the termination of the cardiopulmonary bypass and 2 h thereafter. Out of 119 enrolled patients, 51 (43%) developed AKI. A model utilizing an NGAL, CysC and creatinine triple biomarker panel including sequential relative changes provides a better prediction of cardiac surgery-associated acute kidney injury than any biomarker alone already 2 h after the termination of the cardiopulmonary bypass. The area under the receiver-operator curve was 0.77, sensitivity 77% and specificity 68%.

How to Really Understand and Improve the System of Internal Quality Control and External Quality Assessment in the Accreditation Process of the Medical Laboratory?

Internal quality control (IQC) regarding process to monitor analytical stability has a long tradition in laboratory medicine. The satisfactory results with different quality specifications of the IQC ensure the acceptability of the examination results. Although the statistical IQC is satisfactory some problems exist, resulting in unreliable patients' results due several reasons (non-commutable control materials, lot to lot difference of reagents, false interpreting test results regarding autovalidation or autoverification, different analytical and clinical specifications or goals etc.). Therefore, the results and findings of IQC have to be connected with external quality assessment (EQA) in order to provide the system of measurement of uncertainty (MU) with correct interpretation of laboratory result and detection relevant and significant shifts and drifts in medical laboratory.

Serum Klotho as a marker for early diagnosis of acute kidney injury after cardiac surgery.

BACKGROUND: Early diagnosis of acute kidney injury (AKI) after cardiac surgery is based on serum creatinine which is neither a specific nor a sensitive biomarker. In our study, we investigated the role of serum Klotho in early prediction of AKI after cardiac surgery using cardiopulmonary bypass (CPB). METHODS: The included patients were classified into three groups according to AKI stages using KDIGO criteria. The measurements of creatinine and Klotho levels in serum were performed before surgery, at the end of CPB, 2 hours after the end of CPB, 24 hours and 48 hours postoperatively. RESULTS: Seventy-eight patients were included in the study. A significant increase of creatinine levels (p<0.001) was measured on the first day after the surgery in both AKI groups compared to the non-AKI group. However, a significant difference between AKI-2 and AKI-1 groups (p=0.006) was not measured until the second day after the operation. Using decision trees for classification of patients with a higher or lower risk of AKI we found out that Klotho discriminated between the patients at low risk of developing more severe kidney injury in the first hours after surgery and the patients at high risk better than creatinine. Adding also the early measurements of creatinine in the decision tree model further improved the prediction of AKI. CONCLUSIONS: Serum Klotho may be useful to discriminate between the patients at lower and the patients at higher risk of developing severe kidney injury after cardiac surgery using CPB already in the first hours after surgery.

Association of biomarker S100B and cerebral oximetry with neurological changes during carotid endarterectomy performed in awake patients.

Background: This study attempted to correlate neurological symptoms in awake patients undergoing carotid endarterectomy (CEA) under local anaesthesia (LA) with serum concentration of S100B protein and measurement of cerebral oximetry with near-infrared spectroscopy (NIRS). Patients and methods: A total of 64 consecutive CEAs in 60 patients operated under LA during an 18-month period were prospectively evaluated. A cerebral oximeter was used to measure cerebral oxygen saturation (rSO2) before and after cross-clamping along with serum concentration of the S100B protein. Selective shunting was performed when neurological changes occurred, regardless of NIRS. Neurological deterioration occurred (neurological symptoms group) in 7 (10.9 %) operations. In 57 (89.1 %) operations, the patients were neurologically stable (no neurological symptoms group). Results: The neurological symptoms that occurred after clamping correlated with an increase in the serum level of S100B (P = .040). The cut-off of 22.5 % of S100B increase was determined to be optimal for identifying patients with neurological symptoms. There was no correlation between rSO2 decline and neurological symptoms (P = .675). Two (3.1 %) perioperative strokes occurred. Conclusions: We found a correlation between neurological symptoms and serum S100B protein increase. However, because of the long evaluation time of serum S100B, this monitoring technique cannot be performed during CEA.

The top-down approach to measurement uncertainty: which formula should we use in laboratory medicine?

INTRODUCTION: By quantifying the measurement uncertainty (MU), both the laboratory and the physician can have an objective estimate of the results' quality. There is significant flexibility on how to determine the MU in laboratory medicine and different approaches have been proposed by Nordtest, Eurolab and Cofrac to obtain the data and apply them in formulas. The purpose of this study is to compare three different top-down approaches for the estimation of the MU and to suggest which of these approaches could be the most suitable choice for routine use in clinical laboratories. MATERIALS AND METHODS: Imprecision and bias of the methods were considered as components of the MU. The bias was obtained from certified reference calibrators (CRC), proficiency tests (PT), and inter-laboratory internal quality control scheme (IQCS) programs. The bias uncertainty, the combined and the expanded uncertainty were estimated using the Nordtest, Eurolab and Cofrac approaches. RESULTS: Using different approaches, the expanded uncertainty estimates ranged from 18.9-40.4%, 18.2-22.8%, 9.3-20.9%, and 7.1-18.6% for cancer antigen (CA) 19-9, testosterone, alkaline phosphatase (ALP), and creatinine, respectively. Permissible values for MU and total error ranged from 16.0-46.1%, 13.1-21.6%, 10.7-26.2%, and 7.5-17.3%, respectively. CONCLUSION: The bias was highest using PT, followed by CRC and IQCS data, which were similar. The Cofrac approach showed the highest uncertainties, followed by Eurolab and Nordtest. However, the Eurolab approach requires additional measurements to obtain uncertainty data. In summary, the Nordtest approach using IQCS data was therefore found to be the most practical formula.

Defining the Optimal Size of Medical Laboratories at the Primary Level of Health Care with Data Envelopment Analysis: Defining the Efficiency of Medical Laboratories.

INTRODUCTION: As an integral part of health care, biomedical laboratories are an important contributor to quality patient care. There are only few studies on technical and economic efficiency in the field of laboratory medicine. Nevertheless, such research is crucial to further optimize public resources. AIM: The aim of our research is to create and verify a model for defining the scale efficiency of medical laboratories at the primary level of health care. METHODS: Twenty-one laboratories at the primary level of health care in Slovenia were included in the analysis. The efficiency of medical laboratories was determined using data envelopment analysis. We additionally used hierarchical cluster analysis to determine the homogeneous groups within the analyzed sample of units. RESULTS: We determined the high technical and pure technical efficiency of the analyzed laboratories. The analysis results showed that changes in work processes represent only a minuscule improvement in efficiency, while more can be achieved through a proper scaling of laboratory services. The impact of the operating scale on the efficiency of laboratories is up to twice as high as the process inefficiency. If we take into account the operating modes of laboratories, the optimal scale of services starts at 237,570 automatic tests. CONCLUSIONS: We note that increased automation and consolidation of laboratory activities could contribute to a greater efficiency of medical laboratories and consequently reduce public spending. DEA is an appropriate tool for the efficiency analysis of public medical laboratories and of appropriate support for policy creation and evaluation in the field of laboratory medicine.

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

BACKGROUND: Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. METHODS: Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. RESULTS: Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. CONCLUSION: Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance.

Validity of Klotho, CYR61 and YKL-40 as ideal predictive biomarkers for acute kidney injury: review study / Validade de Klotho, CYR61 e YKL-40 como biomarcadores preditivos ideais para lesão renal aguda: estudo de revisão

ABSTRACT CONTEXT AND OBJECTIVE: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity. Here, we reviewed previous studies conducted on the Klotho, CYR61 and YKL-40 biomarkers in relation to AKI. DESIGN AND SETTING: Review of the literature conducted in the Institute of Clinical Chemistry & Biochemistry, Ljubljana University Medical Center, Slovenia. METHODS: The literature was searched in PubMed and the Cochrane Library. From the database of this specialty, we selected 17 references that matched our context for detailed analysis and further investigation. RESULTS: The studies reviewed showed notable differences in their results relating to the diagnostic impact of Klotho, CYR61 and YKL-40 on early prediction of AKI. CONCLUSIONS: The results regarding the Klotho, CYR61 and YKL-40 biomarkers showed markedly equivocal performance in the previous studies and did not fulfill the expectations that these factors would form valid possible biomarkers for AKI.

RESUMO CONTEXTO E OBJETIVO: A lesão renal aguda (LRA) ainda é uma dor de cabeça para os clínicos e cientistas como possível razão para o aumento da mortalidade entre os pacientes de unidade de terapia intensiva (UTI) após cirurgia cardíaca invasiva. Além disso, o processo de diagnóstico para LRA usando biomarcadores convencionais não é suficiente para garantir um alerta precoce desta condição, devido à influência mórbida de fatores não renais que podem retardar o tempo para o prognóstico. Essas limitações geraram quantidades significativas de pesquisas orientadas para identificar novos biomarcadores para LRA com um grau adequado de sensibilidade e especificidade. Revisamos estudos anteriores realizados sobre os biomarcadores Klotho, CYR61, YKL-40 para LRA. TIPO DE ESTUDO E LOCAL: Revisão da literatura realizada no Instituto de Química Clínica e Bioquímica, Centro Médico da Universidade de Ljubljana, Eslovênia. MÉTODOS: A literatura foi pesquisada no PubMed e Cochrane Library. A partir da base de dados da especialidade, selecionamos 17 referências que combinavam com o contexto para uma análise detalhada e mais investigação. RESULTADOS: Os estudos revisados mostraram diferenças notáveis nos resultados sobre o impacto diagnóstico de Klotho, CYR61 e YKL-40 sobre a detecção precoce do LRA. CONCLUSÃO: Os resultados em relação aos biomarcadores Klotho, CYR61 e YKL-40 mostraram desempenho marcadamente equívoco nos estudos anteriores e não cumpriram as expectativas de que estes fatores constituam possíveis biomarcadores válidos para LRA.

Validity of Klotho, CYR61 and YKL-40 as ideal predictive biomarkers for acute kidney injury: review study.

CONTEXT AND OBJECTIVE:: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity. Here, we reviewed previous studies conducted on the Klotho, CYR61 and YKL-40 biomarkers in relation to AKI. DESIGN AND SETTING:: Review of the literature conducted in the Institute of Clinical Chemistry & Biochemistry, Ljubljana University Medical Center, Slovenia. METHODS:: The literature was searched in PubMed and the Cochrane Library. From the database of this specialty, we selected 17 references that matched our context for detailed analysis and further investigation. RESULTS:: The studies reviewed showed notable differences in their results relating to the diagnostic impact of Klotho, CYR61 and YKL-40 on early prediction of AKI. CONCLUSIONS:: The results regarding the Klotho, CYR61 and YKL-40 biomarkers showed markedly equivocal performance in the previous studies and did not fulfill the expectations that these factors would form valid possible biomarkers for AKI.

Creatinine, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C in Determining Acute Kidney Injury After Heart Operations Using Cardiopulmonary Bypass.

Acute kidney injury (AKI) represents frequent complication after cardiac surgery using cardiopulmonary bypass (CPB). In the hope to enhance earlier more reliable characterization of AKI, we tested the utility of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in addition to standard creatinine for early determination of AKI after cardiac surgery using CPB. Forty-one patients met the inclusion criteria. Arterial blood samples collected after induction of general anesthesia were used as baseline, further sampling occurred at CPB termination, 2 h after CPB, on the first and second day after surgery. According to AKIN classification 18 patients (44%) developed AKI (AKI1-2 groups) and 23 (56%) did not (non-AKI group). Groups were similar regarding demographics and operative characteristics. CysC levels differed already preoperatively (non-AKI vs. AKI2; P = 0.045; AKI1 vs. AKI2; P = 0.011), while postoperatively AKI2 group differed on the first day and AKI1 on the second regarding non-AKI group (P = 0.004; P = 0.021, respectively). NGAL and creatinine showed significant difference already 2 h after CPB between groups AKI2 and non-AKI and later on the first postoperative day between groups AKI1 and AKI2 (P = 0.028; P = 0.014, respectively). This study shows similar performance of early plasma creatinine and NGAL in patients with preserved preoperative renal function. It demonstrates that creatinine, as well as NGAL, differentiate subsets of patients developing AKI of clinically more advanced grade early after 2 h, also when used single and uncombined.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

AIM: To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). METHODS: The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. RESULTS: Patients with T1D had significantly higher levels of blood glucose (P<0.001), fructosamine (P<0.001), and 8-OHdG (P<0.001), but there were no significant differences in triglycerides (P=0.108), cholesterol (P=0.531), and LDL (P=0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11±0.15 vs 1.24±0.23; P=0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r=0.58; P<0.001), fructosamine (r=0.46; P=0.003), 8-OHdG (r=0.48; P=0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2=0.38, P<0.001). CONCLUSION: Higher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

The "Rise-Peak-Fall" Pattern of Time Dependency of the Cardiovascular Pleiotropic Effects of Treatment With Low-dose Atorvastatin, Losartan, and a Combination Thereof in Rats.

Treatment with low, subtherapeutic doses of statins and sartans expresses beneficial pleiotropic effects on the arterial wall. The present study explored whether these effects depend on treatment duration. Wistar rats were randomly divided into 4 groups and received low-dose atorvastatin, low-dose losartan, their combination, or saline (control) daily. After 4, 6, 8, and 10 weeks of treatment, the animals were anesthetized, blood samples taken, and hearts and thoracic aortas isolated. Thoracic aorta endothelium-dependent relaxation and parameters of the isolated heart exposed to ischemic-reperfusion injury were assessed along with blood serum parameters and vasoactive genes expression. Low-dose atorvastatin, losartan, and especially their combination showed the characteristic time dependency of all studied parameters (thoracic aorta relaxation, isolated heart parameters, C-reactive protein values, genes encoding endothelial nitric oxide synthase, and CD40). The peak in efficacy was observed after 6 weeks of treatment and subsequently steadily declined. The peak versus control values were significant for all measured parameters. Only a combination of atorvastatin and losartan increased nitric oxide and decreased asymmetric dimethylarginine. A characteristic time-dependent "rise-peak-fall" pattern of the cardiovascular pleiotropic effects of statins and sartans in subtherapeutic low doses was revealed. Evidently, resistance to the explored treatment occurs after a certain period.

Evaluation of serum cysteine-rich protein 61 and cystatin C levels for assessment of acute kidney injury after cardiac surgery.

Objective The occurrence of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) can lead to morbidity and mortality. We hypothesized that cysteine-rich protein 61 (CYR61) and cystatin C (CysC) may be potential novel biomarkers of AKI after cardiopulmonary bypass. Methods Patients were classified into AKI and non-AKI group depending on serum creatinine. Levels of creatinine, CysC, and CYR61 were measured at five time-points before and within 48 h after the surgery. Results Fifty patients were included in the study. Serum creatinine pre-operative values were 74.0 ± 43.3 µmol/L in AKI group vs. 64.8 ± 17.9 µmol/L in non-AKI group. During 48 h, the values increased to 124.6 ± 67.2 µmol/L in AKI group (p < 0.001) but in non-AKI group they did not change significantly. Serum CysC values were significantly increased already 2 h after CBP in AKI group (949 ± 557 µg/L, p < 0.05) compared to non-AKI group (700 ± 170 µg/L). Pre-operative serum CYR61 tended to be lower in AKI group (12.4 µg/L) than in non-AKI group (20.3 µg/L), but 24 h after the surgery, the levels in AKI group tended to be higher than non-AKI group. Conclusion Serum CYR61 does not seem to be an early predictor of AKI in patients after cardiac surgery with CPB, but it might possibly identify patients at risk of developing more severe kidney injury. Serum CysC could be a promising biomarker of AKI, differentiating patients at risk of developing AKI after cardiac surgery as early as 2 h after surgery.

Proenkefalin A and protachykinin in ischemic neurological complications after cardiac surgery.

AIM: The evaluation of biomarkers of acute ischemic brain injury following surgical revascularization of the heart with the use of the heart-lung machine (cardiopulmonary bypass, CPB). METHODS: Twenty consecutive patients were divided into two groups: the first 10 patients received a potential neuroprotective human recombinant erythropoietin, while the remaining 10 comprised the control group. Neurological complications were monitored by measuring serum concentrations of neuropeptide proenkephalin A(PENK-A) and protachykinin A (PTA) before and in the first 5 days after surgery, comparing the neurological outcome with MRI examinations. RESULTS: Both the erythropoietin-treated group and control group were comparable with a non-significant difference shown for the postoperative concentrations of PENK-A and PTA. A comparison of serum concentrations of the biomarkers of 16 patients without brain ischemia and 4 patients with acute ischemia also displayed no significant differences, regardless of erythropoietin therapy. CONCLUSION: In our pilot study the analysis of PENK-A and PTA serum concentrations might not be the strategy to enable the monitoring and evaluation of neuroprotective stroke treatment, but further studies are required to investigate its role in acute ischemic brain injury.

Glycogen phosphorylase isoenzyme BB, creatine kinase isoenzyme MB and troponin I for monitoring patients with percutaneous coronary intervention - a pilot study.

AIM: The glycogen phosphorylase isoenzyme BB (GPBB), as an ischemic marker, has not yet been investigated after elective percutaneous coronary intervention (PCI). ose aim of the study was to monitor GPBB, creatine kinase myocardial isoform (CK-MB) mass) and troponin I (TnI) value after PCI in correlation with ischemic incidents. METHODS: Forty-two consecutive patients undergoing elective PCI were included in the study. Baseline blood samples and two more after the PCI (3 and 24 hours) were taken. The significance of cardiac markers in twenty-ththe stable patients with baseline values of CK-MB mass and TnI below the upper reference limit (URL) was evaluated based on ischemic incidents after PCI. RESULTS: TnI value was the only biomarker that was statistically significant at 3 and 24 hours after PCI in group of 23 stable patients. An overall comparisonthe biomarkers of 18 patients without and five patients with ischemic incidents displayed significant differences only for the baseline GPBB (p=0.019) and CK-MB mass 24 hours after PCI (p=0.034). Ischemic incidents were independently predictable only based on overall CK-MB mass measurements (OR=1.680, p=0.041) and particularly GPBB at baseline (OR=1.899, p=0.008) and CK-MB mass 24 hours after PCI (OR=2.111, p=0.022). CONCLUSIONS: Only significant increases in TnI were observed after elective PCI with ischemic incidents predicted using GPBB and CK-MB mass measurements.

Antiinflammatory effect of sevoflurane in open lung surgery with one-lung ventilation.

AIM: To prospectively assess the antiinflammatory effect of volatile anesthetic sevoflurane in patients undergoing open lung surgery with one lung ventilation (OLV). METHODS: This prospective, randomized study included 40 patients undergoing thoracic surgery with OLV (NCT02188407). The patients were randomly allocated into two equal groups that received either propofol or sevoflurane. Four patients were excluded from the study because after surgery they received blood transfusion or non-steroid antiinflammatory drugs. Inflammatory mediators (interleukins 6, 8, and 10, C-reactive protein [CRP], and procalcitonin) were measured perioperatively. The infiltration of the nonoperated lung was assessed on chest x-rays and the oxygenation index was calculated. The major postoperative complications were counted. RESULTS: Interleukin 6 levels were significantly higher in propofol than in sevoflurane group (P=0.014). Preoperative CRP levels did not differ between the groups (P=0.351) and in all patients they were lower than 20 mg/L, but postoperative CRP was significantly higher in propofol group (31±6 vs 15±7 ng/L; P=0.035); Pre- and postoperative procalcitonin was within the reference range (<0.04 µg/L) in both groups. The oxygenation index was significantly lower in propofol group (339±139 vs 465±140; P=0.021). There was no significant difference between the groups in lung infiltrates (P=0.5849). The number of postoperative adverse events was higher in propofol group, but the difference was not-significant (5 vs 1; P=0.115). CONCLUSION: The study suggests an antiinflammatory effect of sevoflurane in patients undergoing thoracotomy with OLV.

Low-dose atorvastatin, losartan, and particularly their combination, provide cardiovascular protection in isolated rat heart and aorta.

Statins and angiotensin receptor blockers at therapeutic doses have beneficial cardiovascular effects, which can be applied for cardiovascular protection. We explored whether low doses of atorvastatin, losartan, and particularly their combination, possess important pleiotropic vasodilatory effects. Wistar rats were treated daily with low-dose atorvastatin (2 mg/kg, n = 15), low-dose losartan (5 mg/kg, n = 15), their combination (n = 15), or saline (n = 15). After 4, 6, or 8 weeks the animals were anesthetized, blood samples taken, and their hearts and thoracic aortas isolated. Two kinds of experiments were performed: the measurement of coronary flow rate after ischemia/reperfusion myocardial injury and endothelium-dependent relaxation of thoracic aorta. In both models, maximal vasodilation activity was obtained in rats treated for 6 weeks. In the ischemia/reperfusion myocardial injury model, coronary flow increased (atorvastatin or losartan 1.9-fold, P < 0.01; combination 2.4-fold, P < 0.001) compared with controls. In the thoracic aorta model, endothelium-dependent relaxation significantly increased only in the combination group compared with the control group (up to 1.4-fold; P < 0.01). Simultaneously, we detected increased anti-inflammatory activity and increased nitric oxide concentration, but no changes in lipids and blood pressure. In a rat model we showed important vasodilatory activity of low-dose atorvastatin, losartan, and particularly their combination. The effects of the low-dose combination were accompanied by, and probably at least partly achieved by, anti-inflammatory and nitric oxide pathways. Overall, these results could be valuable for the development of new vascular protective strategies focusing on a low-dose regimen of statins and sartans, and particularly their combination.

The effects of 8 weeks of endurance running on hepcidin concentrations, inflammatory parameters, and iron status in female runners.

Exercise-associated iron deficiency is a common disorder in endurance athletes. The authors investigated the effects of long-term endurance exercise on hepcidin concentrations, inflammatory parameters, and iron status in moderately trained female long-distance runners. Eighteen runners were assigned to either an interval- or a continuous-training exercise group. The physical training consisted of two 3-week progressive overload periods, each followed by a week's recovery, and concluded with a 10- or 21-km competitive run. Samples were taken 6 times during the 8-wk training program, first at baseline (BPre), then after the first and second 3-wk training loads (TPost1, TPost2), after each recovery week (Recovery1 and Recovery2), and poststudy (BPost). Soluble transferrin receptor (sTfR) concentrations were increased in Recovery2 and BPost compared with BPre (p=.02), hemoglobin decreased in TPost1 and TPost2 (p<.001), and red blood cells decreased in TPost2 (p=.01). Hepcidin decreased with time in TPost1 and in BPost compared with BPre (p<.001) and increased in TPost2 compared with TPost1 (p<.001). No differences over time were found for high-sensitivity C-reactive protein. The main findings of the current study indicate that serum hepcidin and sTfR were affected after 8 weeks of endurance running in women. No positive relation was found with inflammation.