Two cases with discrepancy in the quantitative cytological assessment of cerebrospinal fluid in neonatal samples using light microscopy in comparison with Sysmex XN-1000.

We present two cases from the neonatal department with cerebrospinal fluid examination. We revealed a striking discrepancy in polymorphonuclear (PMN) and mononuclear (MN) cell counts using conventional light microscopy in comparison with automated analyzer Sysmex XN-1000 (PMNs - 13 vs. 173x106/L, MNs - 200 vs. 67x106/L in case 1 and PMNs - 13 vs. 372x106/L, MNs - 411 vs. 179x106/L in case 2). We revealed the dominant presence of hemosiderophages in both cases in cytospin slide. Even though Sysmex XN-1000 offers fast examination with a low sample volume, there is possibility of misdiagnosis, with negative impact on the patient.

Comparison of two methods for dimethylarginines quantification.

Objectives: Both dimethylarginines are widely bound to chronic kidney disease (CKD). This study was focused to validate published LC-MS/MS method and compared the measured data with an immunoassay. Design and methods: The analysis was performed on a Dionex UltiMate 3000 UHPLC-Standard (Thermo Fisher Scientific, Waltham, Massachusetts, USA) with an amaZon SL ion trap (Bruker, Billerica, Massachusetts, USA). Comparison was evaluated by using Passing Bablok regression and Bland Altman plot. Healthy volunteers (n = 40) were used for validation and as control group to patients group (n = 40) with different stages of CKD. Results: The results in healthy controls determined by the LC-MS/MS (ELISA) method were 0.52 ± 0.0892 with 95 % CI: 0.49-0.55 (0.61 ± 0.1213 with 95 % CI: 0.57-0.64) µmol/L for AD MA and 0.56 ± 0.0810 with 95 % CI: 0.53-0.58 (0.62 ± 0.0752 with 95 % CI: 0.57-0.65) µmol/L for SDMA. In the same way, the patient group values determined by the LC-MS/MS (ELISA) method were 0.82 ± 0.1604 with 95 % CI: 0.75-0.88 (1.06 ± 0.3002 with 95 % CI: 0.94-1.19) µmol/L and 2.14 ± 0.8778 with 95 % CI: 1.47-2.58 (1.65 ± 0.5160 with 95 % CI: 1.40-1.98) µmol/L for ADMA and SDMA, respectively. The correlation between the methods, expressed as the Spearman correlation coefficient (R), was 0.858 (0.8059) for ADMA (p < 0.0001) and 0.895 (0.9607) for SDMA (p < 0.0001). Conclusions: ADMA levels determined by the immunoassay were almost 30 % overestimated, in contrast to SDMA levels, which were 3 % underestimated. According to our findings, a better correlation could be obtained by simple sample dilution.

Arrhythmias and laboratory abnormalities after an electrical accident: a single-center, retrospective study of 333 cases.

BACKGROUND: Even though electrical injuries are common in the emergency room, guidelines, consensus, and general recommendations for the management of these patients do not exist in Europe. Documented cases of delayed arrhythmias are rare and their connection with electrical injury has not been fully confirmed. We also use cardio-specific markers for the risk stratification of myocardial injury, but there is no significant study referring to their utility in this clinical situation. These reasons led us to retrospectively analyze all cases of electrical injuries over 23 years to determine the prevalence of cardiac arrhythmias (mainly malignant arrhythmias and delayed arrhythmias). METHODS: We retrospectively searched all patients admitted to the University Hospital in Pilsen, CZ, with a diagnosis of electric injury (ICD diagnostic code T754) from 1997 to 2020. The hospital´s information system was used to research the injury; data were drawn from patient medical records. RESULTS: We identified 333 cases of electrical injury in our hospital. Men accounted for about two-thirds, and women one-third. Children accounted for about one-third of cases. Most were low-voltage injuries (< 1000 V, 91.6%). All participants had an initial ECG, and 77.5% of patients had continuous ECG monitoring, usually lasting 24 h. Cardiac arrhythmias were noticed in 39 patients (11.7%). The most frequent arrhythmias were: ventricular fibrillation, sinus tachycardia, bradycardia and arrhythmia, atrial fibrillation, and supraventricular tachycardia. The ECG showed cardiac conduction abnormalities in 28 patients (8.1%), and ten patients (3%) had supraventricular or ventricular extrasystoles. In ten cases (3%), we found changes in ST segments and T waves on the initial ECG. Thirty-one patients (9.3%) suffered a loss of consciousness and 50 patients (15.02%) reported paresthesia. The most frequent ion disbalances were hypokalemia (18%) and hypocalcemia (3.3%). Patients with an ion disbalance had significantly more arrhythmias and newly diagnosed cardiac conduction abnormalities. Troponin levels (cTnI or hs-cTnT) were measured in 258 cases (77.48%) and found to be elevated above the 99th percentile in 19 cases (5.7%). Almost one-third of patients had burns of various degrees of seriousness, and 41 patients (12.3%) had concomitant traumatic injuries. Eleven patients underwent pre-hospital resuscitation, three died in the hospital, and another died as result of intracranial hemorrhage. CONCLUSION: All malignant arrhythmias occurred immediately after the electrical injury, delayed life-threatening arrhythmias were not observed, and no predictive factors of malignant arrhythmias were found. While elevations of cardiac troponins were observed sporadically, they did not appear helpful for risk stratification. In patients with arrhythmias, ion disbalance may be more critical. We concluded that asymptomatic, uninjured adult and pediatric patients with normal initial ECG findings do not need continuous ECG monitoring and may be discharged home. Recommendations for high-risk patients and patients with mild ECG abnormalities at admission are less obvious.

False positive result of human chorionic gonadotropin caused by human anti-mouse antibodies.

Immunochemical reactions are fast, can be automated, and generally do not require pretreatment of biological material. Based on these advantages, they are widely used. On the other hand, they are susceptible to analytical interference that can lead to inaccurate results. These factors include the presence of anti-mouse antibodies, causing false positive (or sometimes false negative) results. Although the anti-mouse antibodies over many decades have been repeatedly identified to be the causative source but due to the rarity of such encounters they remain insufficiently considered. Here we show a case, a 45 year-old female who was mis-diagnosed with pregnancy due to falsely elevated human chorionic gonadotropin (hCG) due to anti-mouse antibodies. This led to the patient undergoing two ultrasound examinations and laparoscopy before the hCG was repeated on alternative assays which showed negative results, preventing the patient from methotrexate treatment. Here we describe the details of the case, outline the assay principal, supporting the finding from literature and outlining a process on how to identify such interferences in timely manner.

Macrotroponins cause discrepancy in high-sensitivity examination.

AIM: We present two cases with clearly discrepant results of clinical examination and cardiac troponin I (cTnI) and cardiac troponin T (cTnT) concentrations. In similar cases with discrepant results, the possibility of interference should be considered. METHODS: Due to the suspicion of the presence of macrotroponin I in both of the presented cases, the patients were invited to our laboratory and both cTnI (Architect i1000, Abbott) and cTnT (Cobas 8000, Roche) concentrations were analysed. The samples were treated by preincubation in a heterophilic antibodies blocking tube (HBT) and analysed. Precipitation with polyethylene glycol solution (PEG) and molecular weight separation by gel filtration on Sephadex G100 was performed and concentrations of cTnI were analysed. RESULTS: In the same blood sample, the cTnT and cTnI concentrations were 7 and 1782 ng/L, respectively, in Case 1, and 6 and 96 ng/L, respectively, in Case 2. Incubation of samples in HBT had no significant effect. CTnI concentrations after precipitation with PEG - presented as the percentage of initial concentrations - were 7.4% in Case 1 (and 26.8% in the control sample) and 1.4% in Case 2 (and 56.0% in the control sample). These results indicate a significant decrease in both cases, supporting presence of macrotroponin I. Finally, analyses of cTnI concentrations after gel filtration also supported the presence of macrotroponin I. CONCLUSION: The present cases show that the presence of macrotroponin can lead to unnecessary investigation of the patient. When the possibility of interference is suspected, cooperation with laboratory staff to help with interpretation or to perform more detailed analysis is crucial.

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. BACKGROUND: We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. METHODS: Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. RESULTS: MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. CONCLUSIONS: Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study.

Introduction: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. Background: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. Methods: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. Results: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. Conclusions: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.

TdP Incidence in Methoxamine-Sensitized Rabbit Model Is Reduced With Age but Not Influenced by Hypercholesterolemia.

Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling, and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to torsades de pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in three experimental groups of Carlsson's rabbit model: (1) young rabbits (YC, young control, age 12-16 weeks), older rabbits (AC, adult control, age 20-24 weeks), and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20-24 weeks). TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits, and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low-risk individuals.

Practical guide for identifying unmet clinical needs for biomarkers.

The development and evaluation of novel biomarkers and testing strategies requires a close examination of existing clinical pathways, including mapping of current pathways and identifying areas of unmet need. This approach enables early recognition of analytical and clinical performance criteria to guide evaluation studies, in a cyclical and iterative manner, all the time keeping the clinical pathway and patient health outcomes as the key drivers in the process. The Test Evaluation Working Group of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM TE-WG) https://www.eflm.eu/site/page/a/1158 has published a conceptual framework of the test evaluation cycle which is driven by the clinical pathway, inherent to which is the test purpose and role within the pathway that are defined by clinical need. To supplement this framework, the EFLM TE-WG has also published an interactive checklist for identifying unmet clinical needs for new biomarkers; a practical tool that laboratories, clinicians, researchers and industry can equally use in a consistent manner when new tests are developed and before they are released to the market. It is hoped that these practical tools will provide consistent and appropriate terminology in this diverse field and offer a platform that facilitates greater consultation and collaboration between all stakeholders. The checklist should assist the work of all colleagues involved in the discovery of novel biomarkers and implementation of new medical tests. The tool is aligned with the IOM recommendations and the FDA and CE regulating body's requirements.

High-sensitivity Troponins after a Standardized 2-hour Treadmill Run.

BACKGROUND: The aim of this study was to examine high-sensitivity troponin T and I (hsTnT and hsTnI) after a treadmill run under laboratory conditions and to find a possible connection with echocardiographic, laboratory and other assessed parameters. METHODS: Nineteen trained men underwent a standardized 2-hour-long treadmill run. Concentrations of hsTnT and hsTnI were assessed before the run, 60, 120 and 180 minutes after the start and 24 hours after the run. Changes in troponins were tested using non-parametric analysis of variance (ANOVA). The multiple linear regression model was used to find the explanatory variables for hsTnT and hsTnI changes. Values of troponins were evaluated using the 0h/1h algorithm. RESULTS: Changes in hsTnT and hsTnI levels were statistically significant (p<0.0001 and p<0.0001, respectively). In a multiple regression model (adjusted R2: 0.60, p=0.005 for hsTnT and adjusted R2: 0.60, p=0.005 for hsTnI), changes in both troponins can be explained by relative left wall thickness (LV), training volume, body temperature after the run and creatinine changes. According to the 0h/1h algorithm, none of the runners was evaluated as negative. CONCLUSIONS: Relative LV wall thickness, creatinine changes, training volume and body temperature after the run can predict changes in hsTnT and hsTnI levels. When medical attention is needed after physical exercise, hsTn levels should be tested only when clinical suspicion and the patient's history indicate a high probability of myocardial damage.

Myocardial fibrosis detected by magnetic resonance in systemic sclerosis patients - Relationship with biochemical and echocardiography parameters.

OBJECTIVES: Systemic scleroderma (SSc) is a rare connective tissue disease presenting with fibrosis affecting skin and internal organs. Cardiovascular magnetic resonance (CMR) with quantification of extracellular volume (ECV) and T1 mapping might help to detect heart involvement. We aimed to evaluate whether myocardial involvement correlates with functional and laboratory parameters. METHODS: Thirty-three asymptomatic SSc patients (29 women, aged 56.6±12.2years) and 20 controls (10 women, 53.7±13.1years) were examined using CMR, echocardiography, functional pulmonary test and laboratory assessment. RESULTS: SSc patients had higher ECV (27.5±2.8 vs. 22.8±1.9%, P<0.0001) and native T1 values (1258.9±51.2 vs. 1192.2±32.6, P<0.0001) compared to controls. Plasma level of growth differentiation factor 15 (GDF-15) and galectin-3 correlated with ECV (r=0.35; P=0.0076 and r=0.38; P=0.0081) and native T1 (r=0.31; P=0.023 and r=0.35; P=0.012). GDF-15 was also negatively correlated with diffusing capacity of the lung for carbon monoxide (r=-0.58; P=0.0004) and positively correlated with modified Rodnan skin score (r=0.59; P=0.0003). Conventional echocardiography parameters were similar in SSc patients and controls. However, the global longitudinal peak systolic strain (GLPS) was lower in SSc patients compared to controls (18.6±1.6 vs. 21.1±1.2%; P<0.0001). GLPS also negatively correlated with native T1 (r=-0.35; P=0.0097), ECV (r=-0.33; P=0.014), GDF 15 (r=-0.31; P=0.022), and galectin-3 (r=-0.37; P=0.0076). CONCLUSIONS: Asymptomatic heart involvement is common in SSc patients and includes focal and diffuse myocardial fibrosis. GDF-15 and galectin-3 were positively correlated with myocardial fibrosis parameters. Future outcome studies must show whether measurement of GDF-15 and galectin-3 in SSC patients might be may be useful in clinical practice.

Influence of pneumatic tube system transport on routinely assessed and spectrophotometric cerebrospinal fluid parameters.

BACKGROUND: Pneumatic tube systems (PTS) are widely used in many hospitals. Using PTS reduces turnaround time (TAT) and can improve patients' outcome. METHODS: We investigated whether clinically significant differences could be observed in CSF samples transported by pneumatic tube in comparison with samples transported by hand. Two aliquots from one sample were sent by PTS and by hand from the department of neurology or neurosurgery and compared. RESULTS: Routine cytological and biochemical assessment was compared in 27 cases. There were no statistically significant changes (transport by hand vs. PTS) in glucose levels [data are expressed as median (minimum-maximum)] at 3.7 (2.5-8.6) mmol/L vs. 3.6 (2.7-8.6) mmol/L, p=0.96 or lactate levels at 1.8 mmol/L (1.1-5.5) vs. 1.8 mmol/L (1.1-5.4). We observed a statistically significant decline in total protein levels in samples transported by PTS at 0.56 g/L (0.19-4.29) vs. 0.49 g/L (0.18-4.3), p=0.008. We observed no changes in erythrocyte count at 5/µL (0-40,000) vs. 5/µL (0-40,106), mononuclear cells at 2/µL (1-145) vs. 3/µL (1-152), or polynuclear cells at 0/µL (0-235) vs. 0/µL (0-352). Spectrophotometric examination was performed in 20 cases. There were no statistically significant differences (transport by hand vs. transport by PTS) in NOA at 0.002 (0.001-1.537) vs. 0.001 (0.001-1.528), p=0.95 or NBA at 0.001 (0.001-0.231) vs. 0.001 (0.001-0.276), p=0.675. Samples transported by PTS were delivered faster than samples transported by courier (transport by hand vs. PTS) at 25 min (10-153) vs. 15 min (4-110), p=0.002. CONCLUSIONS: We found no significant changes in glucose, lactate levels and in any of the cytological parameters assessed, nor were statistically significant changes observed in the spectrophotometric parameters. We found a statistically significant decrease in total protein levels in samples transported by PTS. Transport by PTS can be faster than transport by hand.

Relationship between hsTnI and coronary stenosis in asymptomatic women with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a condition associated with accelerated progression of atherosclerosis in affected individuals. Myocardial assessment using exercise testing in such patients, however, is often difficult to perform. Our objective was to determine the factors associated with severe coronary stenosis using computed tomography (CT) angiography of the coronary arteries in asymptomatic patients with RA. METHODS: Forty-four women with RA were examined using CT angiography to detect atherosclerotic involvement and significant coronary stenosis (>50 %). CT findings were correlated with the cardiovascular risk score, and with classical and most recent parameters of atherosclerosis. RESULTS: CT angiography of the coronary arteries revealed severe stenosis (>70 %) in 9 % of patients. High-sensitivity troponin I level was associated with severe coronary stenosis (odds ratio 6.37; 95 % confidence interval 1.53 - 26.48; P = 0.011). Adjustment for confounders did not alter this result (P = 0.039). In contrast, classical and modified Systemic Coronary Risk Evaluation scores had no value in predicting severe stenosis (P ≥ 0.49). CONCLUSION: The present study showed the possible benefits of a coronary CT angiography in women with RA and asymptomatic ischemic coronary heart disease. Increased levels of high-sensitivity troponin I may be a potential indication for this type of examination. However, further studies are needed to confirm these results.

Prolonged Corrected QT Interval as a Predictor of Clinical Outcome in Acute Ischemic Stroke.

BACKGROUND: This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality. METHODS: We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization. Neurological outcome was assessed by modified Rankin scale (mRS) at discharge. RESULTS: Forty-five (65.2%) patients had prolonged QTc at baseline; only 18 (26.1%) patients had prolonged QTc after 48 hours. Baseline QTc was not associated with neurological outcome (P = .27). However, prolonged QTc after 48 hours was associated with worse mRS at discharge (4.5 [4.0-6.0] versus 2.0 [1.0-3.0]; P < .0001). Patients who deceased during hospitalization (n = 7 [10.1%]) as compared with survivors had more frequently prolonged QTc after 48 hours (38.9 versus 0%; P < .0001), higher level of hsTnI (48.4 [36.1-75.0] versus 8.6 [3.4-26.5]; P = .003), and BNP (334 [224-866] versus 109 [30-190]; P = .014). In univariate analysis, 1-year mortality was associated with prolonged QTc after 48 hours, hsTnI, and BNP. In multivariate analysis, only BNP remained to be associated with 1-year mortality (odds ratio 3.41, 95% confidence interval 1.06-11.03). CONCLUSIONS: QTc interval in patients with acute ischemic stroke is a dynamic parameter. Prolonged QTc after 48 hours, but not baseline QTc, correlated with neurological outcome and 1-year mortality. Patients with prolonged QTc had higher level of hsTnI.

Previous Vaccination and Age are More Important Predictors of Immune Response to Influenza Vaccine than Inflammation and Iron Status in Dialysis Patients.

BACKGROUND/AIMS: The immune response to influenza vaccine may be influenced by many factors, e.g. age, comorbidities or inflammation, and iron status. METHODS: We studied the vaccine-induced production of hemagglutination-inhibition antibodies (HI) in 133 hemodialysis patients (HD) and 40 controls. To identify variables associated with the immune response, uni- and multivariate regression analyses were performed with seroconversion in HI titers as a dependent variable, with demographics, comorbidities, previous vaccination, inflammation, and iron status as independent variables. RESULTS: Seroconversion rates were lower in HD than in controls [43% versus 73% (H1N1 strain; p < 0.05); 43% versus 53% (H3N2; P=NS); 36% versus 62% (B; p < 0.05)]. In both HD and control groups, the predictors of the inferior HI production were pre-vaccination seroprotection, vaccination in the previous season, and old age. We did not find associations between seroconversion rates and inflammation and iron status in the studied populations. This was also true for a subanalysis of patients without pre-vaccination seroprotection. CONCLUSION: The influenza vaccine-induced antibody production was lower in HD than in controls and was independent of inflammation and iron status in both groups. Besides dependence on dialysis, the variables associated with inferior seroconversion rates included pre-vaccination seroprotection, previous vaccination, and old age.

Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine.

UNLABELLED: Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. METHODS: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.

Incidence of severe coronary stenosis in asymptomatic patients with peripheral arterial disease scheduled for major vascular surgery.

BACKGROUND: Peripheral arterial disease (PAD) has the risk equivalent of coronary heart disease. The biochemical parameters associated with functionally significant coronary artery stenosis were investigated in asymptomatic patients with PAD who were scheduled for major vascular intervention. METHODS: A total of 50 PAD patients asymptomatic for coronary heart disease were examined using coronary computed tomography angiography (CTA). A stress myocardial CT perfusion (CTP) test was performed in patients who exhibited coronary stenosis >40%. In patients with stress-induced perfusion defects, the severity of stenosis was assessed using invasive coronary angiography including fractional flow reserve assessment. The CT findings were correlated with both classical and more recently developed parameters of atherosclerosis. RESULTS: According to the combined CT examination (CTA and stress CT perfusion), 36% of patients exhibited significant coronary stenosis. Stress-induced hypoperfusion was observed in 95.7% of severe stenotic lesions. After adjustment for confounders, the level of high-sensitivity troponin I was associated with severe coronary stenosis (OR 1.260 [95% CI 1.054 to 1.505]). Other biochemical parameters did not correlate with coronary stenosis. The annual mortality rate was 4%. CONCLUSIONS: The results of the present study confirm a significant diagnostic contribution of a complex cardiac CT examination in patients scheduled for major vascular surgery. A high prevalence of asymptomatic coronary heart disease was observed in this particular patient group. High-sensitivity measurements of troponin I correlated with the extent of the coronary stenosis.

Asymmetric dimethylarginine and progression of chronic kidney disease: a one-year follow-up study.

BACKGROUND/AIMS: Asymmetric dimethylarginine (ADMA) is a prognostic factor in patients with chronic kidney disease (CKD). However, the relationships among factors influencing the metabolism of ADMA and the CKD progression are not fully understood. METHODS: Serum ADMA, and variables related to the metabolism of ADMA were measured in 181 non-dialysis patients (CKD stages 3-5) and in 46 controls. Patients were assessed at baseline, and 6 and 12 months after the initiation of the study. RESULTS: Patients had increased baseline ADMA, advanced glycation end products (AGE), and advanced oxidation protein products (AOPP) compared with controls (P<0.001). In a total of 164 patients who completed a one-year study, the estimated GFR (eGFR) declined from 23.5 (17.7-36) mL/min/1.73m(2) to 21 (14.7-31.5) (P=0.018), AGE rose from 1.58 (1.38-1.90) µmol/L to 1.76 (1.52-2.21) (P<0.001), while ADMA, AOPP, tubular function, and proteinuria remained stable. In a multiple regression model (adjusted R(2) = 0.49, P<0.0001), the interaction of relatively higher baseline eGFR, i.e. > 25 mL/min/1.73m(2), with higher ADMA (P=0.02) and higher AOPP (P=0.04) predicted the severest decrease in eGFR per year. Other predictors of progression were higher baseline AGE (P<0.001), proteinuria (P=0.003), hypertension (P=0.01), and higher baseline eGFR (P=0.03). CONCLUSION: Elevated ADMA and markers of oxidative stress were strong predictors of progression in patients with eGFR between 25-40 mL/min/1.73m(2) , i.e. at the borderline of CKD stages 3-4.