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Background: Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays., Methods: Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR., Results: We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C., Conclusions: A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced., (© 2014 The American Association for Clinical Chemistry.)

Background: Cystatin C is a promising new biomarker to determine the estimated glomerular filtration. However, the Siemens' cystatin C assay (Siemens), used in many longitudinal studies, has had limited clinical applicability because it requires a specific, dedicated instrument. Other companies, including Gentian and Roche, have developed cystatin C assays that can be used with most routine clinical chemistry analyzers., Methods: We compared the agreement of Gentian and Roche with Siemens assays in 948 participants at the baseline visit of the Heart and Soul Study, a cohort of participants with established coronary artery disease who were followed for an average of 8 years. We then compared associations of all 3 cystatin C measures and eGFR-Modification of Diet in Renal Disease (MDRD) with clinical outcomes., Results: The Gentian assay had higher correlation with Siemens (r = 0.96) than did Roche (r = 0.93, P < 0.001). After cross-tabulating quartiles of each cystatin C measure, agreements (κ statistic) were higher for Siemens and Gentian (0.73, 95% CI 0.72-0.75) than for Roche and Siemens (0.64, 0.63-0.66) or for Roche and Gentian (0.69, 0.65-0.71). These differences in agreement had minimal impact on associations with clinical outcomes; the hazard ratios (HRs) for mortality comparing the high vs low quartiles were 3.2 (95% CI 2.1-4.8) for Siemens, 3.1 (CI 2.1-4.7) for Gentian, 3.1 (CI 2.1-4.7) for Roche, and 1.6 (CI 1.1-2.3) for eGFR-MDRD, after multivariate adjustment., Conclusions: In summary, agreement with the Siemens' assay was modestly higher for the Gentian compared with the Roche assay, although all 3 methods for cystatin C measurement had similar utility as predictors of clinical outcomes.

Objective: Multilevel somatosensory evoked potentials (SSEP) and the release of biochemical markers in cerebrospinal fluid (CSF) were investigated to identify patients with spinal cord ischemia during thoracoabdominal aortic repair and/or a vulnerable spinal cord during the postoperative period., Methods: Thirty-nine consecutive patients undergoing elective aneurysm repair using distal aortic perfusion and cerebrospinal fluid drainage were studied. Continuous SSEP were monitored using nerve stimulation of the right and left posterior tibial nerves with signal recording at the level of both common peroneal nerves, the cervical cord and at the cortical level. CSF concentrations of the markers glial fibrillary acidic protein (GFAp), the light subunit of neurofilament triplet protein (NFL), and S100B were determined at different time points from before surgery until 3 days postoperatively., Results: SSEP indicated spinal cord ischemia in two patients leading to additional intercostal artery reattachments. In one of them the signal loss was permanent and the patient woke up with paraplegia. In the other the signal returned but the patient later developed delayed paraplegia. Three patients without SSEP indications of spinal cord ischemia during surgery later developed delayed paraplegia. The patients with spinal cord symptoms had significant increases, during the postoperative period of CSF biomarkers GFAp (571-fold), NFL (14-fold) and S100B (18-fold) compared to asymptomatic patients. GFAp increased before or in parallel to onset of symptoms in the patients with delayed paraplegia., Conclusions: Peroperative multilevel SSEP has a high specificity in detecting spinal cord ischemia but does not identify all patients with a postoperative vulnerable spinal cord. Biochemical markers in CSF increase too late for intraoperative monitoring but GFAp is promising for identifying patients at risk for postoperative delayed paraplegia.

During the last decade, capillary electrophoresis (CE) has emerged as an important alternative to traditional analysis of serum and plasma proteins by agarose or celluloseacetate electrophoresis. CE analysis of plasma proteins can now be fully automated and also includes bar-code identification of samples, preseparation steps, and direct post-separation quantitation of individual peaks, which permits short assay times and high throughput. For laboratory work, it is important to have reference values from healthy individuals. Therefore, plasma samples from 156 healthy blood donors (79 females and 77 males) have been analyzed with the Capillarys instrument and the new high resolution buffer, which yields higher resolution than the beta1-beta2+ buffer. Albumin concentrations in samples are measured using nephelometry in order to assign protein concentrations to each peak. The 2.5 and 97.5 percentiles for both the percentages of different peaks and the protein concentrations in the peaks are calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. The Capillarys instrument is a reliable system for plasma protein analysis, combining advantages of full automation with high analytical performances and throughput.

Background: Data are sparse regarding the association between C-reactive protein (CRP) and percutaneous coronary intervention (PCI) in long-term prognosis. Previous studies have shown that PCI evokes an inflammatory response. We tested the hypothesis that the CRP response to PCI has a prognostic value., Methods: We investigated 891 consecutive patients presenting with stable or unstable angina pectoris, with serum concentrations of cardiac troponin T < or =0.03 microg/L, who were undergoing a variety of PCIs. Serum concentrations of CRP and cardiac troponin T were determined before and the day after PCI. The mean follow-up time after PCI was 2.6 years, and the endpoint was death or nonfatal myocardial infarction., Results: Seventy-six patients reached the endpoint (4.6% death, 3.9% nonfatal myocardial infarction), whereas 21% developed myocardial infarction during the procedure. CRP increased more than 2-fold after the procedure. Patients in the third tertile of the CRP response to PCI had an increased risk for death or nonfatal myocardial infarction in multivariate analysis., Conclusions: Increased serum CRP in response to PCI is an independent predictor of death or nonfatal myocardial infarction independent of myocardial injury during the procedure. CRP determinations might be of value in risk stratification after PCI.

Objective: Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and retrograde cerebral perfusion, are used to prolong the tolerated duration of circulatory arrest, and the latter may also decrease the possibility of air/particle embolization. The aim of the current study was to investigate whether the neurochemical marker S-100 is related to the duration of circulatory arrest, when the influence of embolic injury has been minimized by the use of retrograde cerebral perfusion during the last part of circulatory arrest., Methods: Arterial serum levels of S-100 were followed before, during and after reconstructive surgery of the thoracic aorta during deep hypothermic arrest in ten adults. Retrograde cerebral blood perfusion was used during the latter part of the arrest period in eight of the ten patients. Neurologic status was followed daily., Results: All patients survived the operation. The median (range) duration of cardiopulmonary bypass (CPB) was 184.5 (121-386) min. The median duration of circulatory arrest and retrograde cerebral perfusion was 50 (3-118) min and 16 (0-84) min, respectively. S-100 increased from 0.10 (0.02-0.18) microg/l preoperatively to 2.37 (0.64-10.80) microg/l after CPB (P<0.01), followed by a decrease to 0.79 (0.21-2.64) microg/l on the first postoperative day (P<0.01). The duration of circulatory arrest correlated with S-100 levels after CPB (r(S) = 0.71, P<0.05) and even better with the S-100 levels on the first postoperative day (r(S) = 0.83, P<0.01). However, there was no significant correlation between duration of arrest and duration of CPB. The duration of circulatory arrest without retrograde cerebral perfusion correlated well with S-100 levels on the first postoperative day (r(S) = 0.88, P<0.01), but not significantly with S-100 levels after CPB., Conclusions: S-100 levels after aortic surgery with deep hypothermic arrest correlate with the duration of circulatory arrest, indicating that the duration of circulatory arrest is damaging to the brain despite the use of deep hypothermia and partial retrograde cerebral perfusion. The highest correlation between S-100 and duration of arrest was seen on the first postoperative day. S-100 appears to perform well under clinical circumstances as a sensitive and discriminative marker for neuronal injury.