The Significance of Blood and Peritoneal Fluid Biochemical Markers in Identifying Early Anastomotic Leak following Colorectal Resection-Findings from a Single-Center Study.

Background and Objectives: The aim of our study was to evaluate the value of leukocyte, C reactive protein (CRP), procalcitonin, lactate, and carcinoembryonic antigen (CEA) in blood and peritoneal fluid in early recognition of anastomotic leak (AL) after colorectal resections. Materials and Methods: Our pilot prospective cohort study was conducted at the abdominal surgery department at University Medical Center Ljubljana. A total of 43 patients who underwent open or laparoscopic colorectal resection because of benign or malignant etiology were enrolled. All of the patients had primary anastomosis without stoma formation. Results: Three patients in our patient group developed AL (7%). We found a statistically significant elevation of serum lactate levels in patients that developed AL compared to those who did not but noted no statistically relevant difference in the blood or peritoneal fluid levels of other biochemical markers. Conclusions: Elevated lactate levels may be considered a promising biomarker for the early diagnosis of AL, but more research on bigger patient groups is warranted.

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%.

Empagliflozin-Metformin Combination Has Antioxidative and Anti-Inflammatory Properties that Correlate with Vascular Protection in Adults with Type 1 Diabetes.

Methods: 40 individuals with type 1 diabetes (average age of 44.7 ± 2.5 years) were randomized into four groups: (1) control (placebo), (2) empagliflozin 25 mg daily, (3) metformin 2000 mg daily, and (4) empagliflozin-metformin combination (25 mg and 2000 mg daily, respectively). At inclusion and after 12 weeks of treatment, the blood samples were collected, and the oxidative stress (total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, advanced oxidation protein products (AOPP), advanced glycosylation end products ((AGE) and isoprostane), and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) parameters were determined. Results: The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001). Antioxidative action was associated with the improvement in arterial function (obtained in the previous study) in the empagliflozin-metformin combination group. Conclusion: Empagliflozin-metformin combination has strong antioxidative and anti-inflammatory capacity, in adults with type 1 diabetes that is greater than that for the individual drugs. Its antioxidative activity at least partially explains the improvement in arterial function. Therefore, it appears that the combination provides the most powerful vascular protection.

No increase in GFAP and S-100B in very preterm infants with mild periventricular leukomalacia or intraventricular hemorrhage: a pilot study.

AIM: To determine the serum levels of glial fibrillary acidic protein (GFAP) and S-100B in very preterm infants with and without periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH). METHODS: The study enrolled preterm infants born between 23 and 32 weeks of gestation admitted to the Neonatal Intensive Care Unit, University Medical Center Ljubljana. PVL and IVH were determined with cranial ultrasound. Peripheral blood was collected in the first 24 hours after delivery and once between days 4 to 7. GFAP and S-100B concentrations were measured in serum samples. Infants with PVL or IVH were compared with infants without PVL or IVH. RESULTS: Of 40 patients (mean gestational age 29.4 weeks), 7 had IVH and/or PVL. S-100B was detectable in peripheral blood in all patients at every measurement. In the group with IVH or PVL, the median S-100B at the first sampling was 0.43 (IQR 0.29-0.60) ng/mL, and 0.40 (IQR 0.33-1.01) ng/mL at the second sampling. In the group without PVL or IVH, it was 0.40 (IQR 0.29-0.6) ng/mL at the first sampling and 0.43 (IQR 0.34-0.62) ng/mL at the second sampling. The median GFAP was 0 regardless of the group and sampling time. The groups did not significantly differ in serum GFAP or S-100B levels. CONCLUSION: Peripheral blood levels of GFAP and S-100B were not significantly increased in very preterm infants that developed PVL or IVH. The predictive value of GFAP and S-100B as biomarkers of neonatal brain injury should be further explored in a larger cohort of neonates with more extensive IVH or PVL.

The Impact of Laryngopharyngeal Reflux on Occurrence and Clinical Course of Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: Laryngopharyngeal reflux (LPR) has been proposed both as a trigger for recurrent respiratory papillomatosis (RRP) onset and as a factor favoring an aggressive clinical course. STUDY DESIGN: In this prospective study, 106 participants were recruited within a period of 24 months at the Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana. METHODS: This study compared a group of RRP patients (N = 36) with a group of LPR patients (N = 28) and a group of healthy participants (N = 42) based on Reflux Symptom Index (RSI), Reflux Finding Scores (RFS), and saliva analyses (pH, pepsin concentration, bile acid concentration, and pepsin enzymatic activity). RESULTS: The RRP group compared to the LPR group showed a statistically significant difference only in RSI and RFS scores, while the RRP group compared to healthy controls showed significantly higher values in all tested parameters (RSI score, RFS, saliva pH, pepsin concentration, bile acids concentration, pepsin enzymatic activity). CONCLUSIONS: LPR is common in RRP patients and significantly more prevalent compared to healthy controls. Our results show that saliva analyses are a better office-based tool than RSI questionnaires and RFS scores for diagnosing LPR in RRP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:619-625, 2022.

Serum hepcidin and ferritin as markers of iron deficiency in premature infants born at less than 32 weeks of gestation: prospective observational study.

BACKGROUND: Preterm infants born at less than 32 weeks of gestation are at higher risk of low total iron stores (iron deficiency). Serum ferritin is used as a valid total iron stores and iron deficiency biomarker, usually as a combination of ferritin and red blood cell counts. METHODS: Serum hepcidin and ferritin values and red blood cell counts were obtained from 37 of 40 included premature infants born at less than 32 weeks of gestation at risk of iron deficiency. The first sample was obtained in the first week of life, and the second at transfer from the Neonatal intensive care unit to the maternity ward, when serum ferritin level below 25 µg/L has been defined as very low total iron stores (iron deficiency). RESULTS: Ferritin median levels decreased from a median value of 152 µg/L at the first measurement to 54 µg/L at the second measurement. Hepcidin median levels also decreased from 30.1 µg/L to 2.1 µg/L. We found a positive and statistically significant correlation between levels of ferritin and hepcidin at both measurements (r = 0.57; p < 0.001 and r = 0.72; p < 0.001, respectively). Compared to serum hepcidin, ferritin at the first measurement has not statistically significant higher power in predicting children with iron deficiency before discharge from the hospital. CONCLUSIONS: We found a correlation between ferritin and hepcidin levels. Nevertheless, hepcidin does not have a worse power in predicting children with iron deficiency compared to ferritin.

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.

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.

Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial.

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1ß, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p < 0.001), IL-6 (until 48 h after surgery, p < 0.001), and IL-8 (until 24 h after surgery, p < 0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5th postoperative day (p < 0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p < 0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).

The Significance of the Sulfatase Pathway for Local Estrogen Formation in Endometrial Cancer.

Endometrial cancer (EC) is the most common estrogen-dependent gynecological malignancy in the developed World. To investigate the local formation of estradiol (E2), we first measured the concentrations of the steroid precursor androstenedione (A-dione) and the most potent estrogen, E2, and we evaluated the metabolism of A-dione, estrone-sulfate (E1-S), and estrone (E1) in cancerous and adjacent control endometrium. Furthermore, we studied expression of the key genes for estradiol formation via the aromatase and sulfatase pathways. A-dione and E2 were detected in cancerous and adjacent control endometrium. In cancerous endometrium, A-dione was metabolized to testosterone, and no E2 was formed. Both, E1-S and E1 were metabolized to E2, with increased levels of E2 seen in cancerous tissue. There was no significant difference in expression of the key genes of the aromatase (CYP19A1) and the sulfatase (STS, HSD17B1, HSD17B2) pathways in cancerous endometrium compared to adjacent control tissue. The mRNA levels of CYP19A1 and HSD17B1 were low, and HSD17B14, which promotes inactivation of E2, was significantly down-regulated in cancerous endometrium, especially in patients with lymphovascular invasion. At the protein level, there were no differences in the levels of STS and HSD17B2 between cancerous and adjacent control tissue by Western blotting, and immunohistochemistry revealed intense staining for STS and HSD17B2, and weak staining for SULT1E1 and HSD17B1 in cancerous tissue. Our data demonstrate that in cancerous endometrium, E2 is formed from E1-S via the sulfatase pathway, and not from A-dione via the aromatase pathway.

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.

Dexamethasone does not diminish sugammadex reversal of neuromuscular block - clinical study in surgical patients undergoing general anesthesia.

BACKGROUND: Sugammadex reverses neuromuscular block (NMB) through binding aminosteroid neuromuscular blocking agents. Although sugammadex appears to be highly selective, it can interact with other drugs, like corticosteroids. A prospective single-blinded randomized clinical trial was designed to explore the significance of interactions between dexamethasone and sugammadex. METHODS: Sixty-five patients who were anesthetized for elective abdominal or urological surgery were included. NMB was assessed using train-of-four stimulation (TOF), with rocuronium used to maintain the desired NMB depth. NMB reversal at the end of anaesthesia was achieved using sugammadex. According to their received antiemetics, the patients were randomized to either the granisetron or dexamethasone group. Blood samples were taken before and after NMB reversal, for plasma dexamethasone and rocuronium determination. Primary endpoint was time from sugammadex administration to NMB reversal. Secondary endpoints included the ratios of the dexamethasone and rocuronium concentrations after NMB reversal versus before sugammadex administration. RESULTS: There were no differences for time to NMB reversal between the control (mean 121 ± 61 s) and the dexamethasone group (mean 125 ± 57 s; P = 0.760). Time to NMB reversal to a TOF ratio ≥0.9 was significantly longer in patients with lower TOF prior to sugammadex administration (Beta = -0.268; P = 0.038). The ratio between the rocuronium concentrations after NMB reversal versus before sugammadex administration was significantly affected by sugammadex dose (Beta = -0.375; P = 0.004), as was rocuronium dose per hour of operation (Beta = -0.366; p = 0.007), while it was not affected by NMB depth before administration of sugammadex (Beta = -0.089; p = 0.483) and dexamethasone (Beta = -0.186; p = 0.131). There was significant drop in plasma dexamethasone after sugammadex administration and NMB reversal (p < 0.001). CONCLUSIONS: Administration of dexamethasone to anesthetized patients did not delay NMB reversal by sugammadex. TRIAL REGISTRATION: The trial was retrospectively registered with The Australian New Zealand Clinical Trials Registry (ANZCTR) on February 28th 2012 (enrollment of the first patient on February 2nd 2012) and was given a trial ID number ACTRN12612000245897 and universal trial number U1111-1128-5104.

Single fiber EMG as a prognostic tool in myasthenia gravis.

INTRODUCTION: Single fiber electromyography (SFEMG) is the most sensitive diagnostic tool for diagnosis of myasthenia gravis (MG). Its prognostic value is not known. METHODS: We retrospectively analyzed the clinical course of 232 MG patients who presented with only mild symptoms and had SFEMG of the orbicularis oculi muscle. We correlated their SFEMG results with the severity of their later clinical course. RESULTS: During the observation period 39 patients (17%) developed severe disease exacerbations, and 193 (83%) remained stable. Patients with severe disease exacerbation had a significantly higher mean jitter value (P < 0.0001), a greater percentage of fibers with increased jitter (P < 0.0001), and/or impulse blocking (P < 0.0001) on SFEMG. CONCLUSIONS: The extent of the SFEMG abnormalities in this study correlated with the later clinical course of MG. Muscle Nerve 54: 1034-1040, 2016.

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.

Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy.

BACKGROUND: The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response. METHODS: The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40-60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery. RESULTS: Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57). CONCLUSIONS: Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia. CLINICAL TRIAL REGISTRATION: Identified as NCT02229201 at www.clinicaltrials.gov.

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.

Higher levels of total pepsin and bile acids in the saliva as a possible risk factor for early laryngeal cancer.

BACKGROUND: Gastroesophageal reflux is suspected to be an etiological factor in laryngeal and pharyngeal cancer. The aim of this study was to establish, using a non-invasive method, whether laryngopharyngeal reflux (LPR) appears more often in patients with early laryngeal cancer than in a control group. PATIENTS AND METHODS: We compared the pH, the level of bile acids, the total pepsin and the pepsin enzymatic activity in saliva in a group of 30 patients with T1 laryngeal carcinoma and a group of 34 healthy volunteers. RESULTS: The groups differed significantly in terms of levels of total pepsin and bile acids in the saliva sample. Higher levels of total pepsin and bile acids were detected in the group of cancer patients. No significant impact of other known factors influencing laryngeal mucosa (e.g. smoking, alcohol consumption, and the presence of irritating substances in the workplace) on the results of saliva analysis was found. CONCLUSIONS: A higher level of typical components of LPR in the saliva of patients with early laryngeal cancer than in the controls suggests the possibility that LPR, especially biliary reflux, has a role in the development of laryngeal carcinoma.