No abstract

Background: Non-cardiac surgery is associated with major vascular complications and higher incidences of elevated plasma troponin (cTn) concentration. Goal-directed therapy (GDT) is a stroke volume (SV)-guided approach to intravenous (IV) fluid therapy that improves tissue perfusion, oxygenation and reduces post-operative complications. In patients undergoing major gastro-intestinal surgery, we compared high sensitive and contemporary troponin assays and correlated results with patient outcome. Methods: Patients (n ¼ 135) were randomized to receive IV fluid, guided by either the central venous pressure (CVP group, n ¼ 45) or SV (AE dopexamine inotrope, n ¼ 45 per group). Serum was obtained pre-and post-operatively (0, 8 and 24 h) for troponin analysis by a prototype hs-cTnI assay (Abbott Laboratories), hs-cTnT (Roche Diagnostics) and contemporary cTnI (Beckman Coulter) assays. Results: All troponin measurements were increased (P 4 0.05) post-operatively but there was no difference (P > 0.05) amongst treatments. Post-operative increases were reported more frequently (P 4 0.05) and earlier with hs-cTnI. Temporal increases (P 4 0.05) were reported in patients with and without complications for hs-cTnI/T assays but only in the complications group for cTnI measurements. Elevations 599th centile occurred most often (P 4 0.05) for hs-cTnT measurements but with similar frequency for both outcome groups (all assays). Only the hs-cTnI assay showed an increased relative risk of mortality (P 4 0.05) for elevations 599th centile Conclusions: Our study may suggest a possible preference for the hs-cTnI assay in the peri-operative setting; however, our findings should be verified for larger cohort studies where emerging reference range data is incorporated for improving risk prediction with hs-cTn assays.

Hypertensive retinopathy manifests itself as progressive retinal microvascular pathology in response to aberrant blood flow. The current study sought to evaluate whether dysfunction of the vasoactive endothelin-1 (ET-1) system is involved in the pathogenesis of hypertension-induced retinopathy in an animal model of systemic hypertension. The endothelin receptor antagonist, bosentan, was administered to spontaneously hypertensive rats (SHRs) and comparisons were made with untreated SHRs and normotensive Wistar Kyoto (WKY) rats. The retinal mRNA expression of ET-1, ET-converting enzyme-1, ET_A and ET_B receptors and the basement membrane proteins, laminin β1, collagen IV and fibronectin was quantified using real-time RT-PCR. In addition, retinal arteriole and/or capillary bed damage was assessed by qualitative and quantitative microscopy. mRNA for the ET_A receptor was increased in SHRs, when compared to WKY control animals (p < 0.001). Treatment with bosentan in SHRs significantly reduced the expression of ET-1 (p < 0.05), and both the ET_A (p < 0.0001) and ET_B (p < 0.05) receptor subtypes. The laminin β1, collagen IV and fibronectin mRNA expression was significantly higher in SHRs when compared to WKY control animals (p < 0.001). Treatment with bosentan abolished these responses and also the appearance of various microvascular lesions. ET-mediated vasoregulation abnormalities in the retinal microvasculature could play an associative role in lesion formation during hypertensive retinopathy.

ObjectivesHigh sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study.Design and methodsAnalytical verification included assessment of critical outlier frequency, for hs-cTnI and cTnI assays. Concordance for paired cTnI and hs-cTnI measurements (n=1096) was verified using 99th percentiles for both genders (cTnI: 30 ng/L, hs-cTnI: 25 ng/L) and for men and women separately (hs-cTnI: M: 34;F: 16 ng/L). Discordant data was correlated with clinical and laboratory information. Diagnosis of Acute Coronary Syndrome (ACS) or Non-ACS was adjudicated by two cardiologists independently.ResultsThe hs-cTnI assay showed a lower (10-fold) critical outlier rate (0.091%) and more detectable results above the limit of detection (LOD) (23.4%) and 99th percentile (2.4%), compared to cTnI. Analytical concordance between the two assays was high (94.5%) but decreased (91.7%) when gender-specific hs-cTnI cut-offs were used. The hs-cTnI assay gave fewer false negatives (up to 1.0%) but disproportionately more false positives (up to 6.7%) overall, which improved (3.9%) for serial measurements.ConclusionsLaboratories should analytically and clinically verify hs-cTn assays before use, with attention to performance and the clinical and diagnostic algorithms that support appropriate testing and result interpretation. Work in the pre- and post-analytical phases is necessary to augment the analytical improvement in the new era of troponin testing.

ObjectivesWhen laboratory Reference Ranges (RR) do not reflect analytical methodology, result interpretation can cause misclassification of patients and inappropriate management. This can be mitigated by determining and implementing method-specific RRs, which was the main objective of this study.Design and methodsSerum was obtained from healthy volunteers (Male + Female, n > 120) attending hospital health-check sessions during June and July 2011. Pseudo-anonymised aliquots were stored (at − 70 °C) prior t° analysis on Abbott ARCHITECT c16000 chemistry and i2000SR immunoassay analysers. Data were stratified by gender where appropriate. Outliers were excluded statistically (Tukey method) to generate non-parametric RRs (2.5th + 97.5th percentiles). RRs were compared to those quoted by Abbott and UK Pathology Harmony (PH) where possible. For 7 selected tests, RRs were verified using a data mining approach.ResultsFor chemistry tests (n = 23), Upper or Lower Reference Limits (LRL or URL) were > 20% different from Abbott ranges in 25% of tests (11% from PH ranges) but in 38% for immunoassay tests (n = 13). RRs (mmol/L) for sodium (138−144), potassium (3.8–4.9) and chloride (102−110) were considerably narrower than PH ranges (133–146, 3.5–5.0 and 95–108, respectively). The gender difference for ferritin (M: 29–441, F: 8–193 ng/mL) was more pronounced than reported by Abbott (M: 22–275, F: 5–204 ng/mL). Verification studies showed good agreement for chemistry tests (mean [SD] difference = 0.4% [1.2%]) but less so for immunoassay tests (27% [29%]), particularly for TSH (LRL).ConclusionWhere resource permits, we advocate using method-specific RRs in preference to other sources, particularly where method bias and lack of standardisation limits RR transferability and harmonisation.