Immune and acute phase markers in exercising adults

Many reports have documented the anti-inflammatory effects of regular exercise in adults. However clinicians and researchers remain uncertain on selecting specific biomarkers that are useful for predicting or monitoring chronic inflammatory states and/or disease. Clearer identification of markers (or clusters of markers) in physically active individuals that vary from established references ranges will indicate the extent of the purported anti-inflammatory effect of regular exercise. Physically active adults were recruited from the community to participate in a prospective study comparing self-reported health outcomes and exercise activity across 150 days of dietary intervention. Of the 450 participants recruited, 64 males (mean age 37.4 y, mean BMI = 25.3) and 59 females (mean age 40.4y, mean BMI= 23.4) agreed to supply a baseline blood sample taken at rest. A total of 187 analytes were measured by standard techniques on these pre-intervention samples including 11 immune markers (cell-types and immunoglobulins) and 11 acute phase reactants (WCC, albumin, haptoglobin, CRP, C3, C4, IGF-1, transferrin, iron, ferritin & ceruloplasmin). We compared baseline values with relevent hospital reference range (RR) values where these are assumed to be more reflective of a much less physically-active community population. A total of 5 out of 11 of the acute phase reactants (Hapt, C3, Fer, Trf (for females), and ceruloplasmin (for males)) had \u3e10% of values below the low ‘cut-off end’ of the relevant RR. Three immune cell-types (CD19, CD8 & CD16/56) had \u3e10% of values below the ‘low-cut-off end’ of the relevant RR. In contrast 25% of subjects had an IgE value that exceeded the RR. Collectively our results support the notion that regular exercise or physical activity exerts an anti-inflammatory affect. The results suggest putative roles for a host of exercise associated adaptive mechanisms beyond the generally accepted role for IL-6 derived from skeletal muscle and\or visceral fat. We conclude that across a host of measures, exercising adults have values for immune and acute phase reactants largely within, but at the non-inflammatory ‘end’ of clinical reference ranges

Neonatal umbilical cord blood cardiac troponin as reflecting fetal growth, age and well being

Objectives: It has been proposed that an elevated concentration of cardiac troponin in umbilical cord blood may function as a surrogate marker of ischemic damage sustained in utero and/or during labour and delivery. The objective of this study is to document the umbilical cord blood concentrations of troponins I (cTnI) and T (cTnT) using high sensitivity assays and correlate these with maternal and fetal clinical history.Methods: Umbilical cord blood was collected immediately following delivery from 416 babies, including 12 sets of twins. Clinical history was obtained from clinical notes. Ethics permission was obtained from ACT Health Human Research and Ethics Committee for the study and consent was obtained from mothers for their participation. Cardiac troponins were assayed using hs- cTnI on Abbott Architect (LoD 1.0 ng/L) and hs-cTnT on Roche E4111 (LoD 5.0 ng/L). Data are expressed as median and 25th and 75th percentiles.Results: Umbilical cord blood consistently has higher median values of cTnT than cTnI such that the median ratios are 6.8 and 5.4 at <32 week gestation and 41 week babies respectively compared with T:I of 0.8 in adults. Babies of early gestation have higher concentrations of cTnT and cTnI as do babies with APGAR scores ≤4 at 1 min. Median cTn concentrations show a 50% decrease between babies born< 32 weeks and those at full term.Relationship of birth weight and umbilical cord cardiac troponin concentrations. Low Birth Weight babies have~50% higher cTn concentrationsConclusions: These findings are consistent with a differential expression of cTnT and cTnI in utero with potential contributions from growth and re-modelling of the heart in addition to “ectopic” production in less differentiated non-cardiac muscle. The effect of intermittent ischemia which occurs as part of normal labour and delivery may superimpose on this increments

Cardiac Biomarkers and the Diagnosis of Myocardial Infarction in Women

PURPOSE OF REVIEW: Women with suspected acute coronary syndrome are less likely to undergo investigation or receive treatment than men, and women consistently have poorer outcomes. This review summarises how the latest development in cardiac biomarkers could improve both diagnosis and outcomes in women. RECENT FINDINGS: Novel high-sensitivity cardiac troponin assays have identified differences in the reference range and therefore diagnostic threshold for myocardial infarction in men and women. These differences are present across multiple populations with different ethnic backgrounds and for a range of assays. The use of a uniform threshold for cardiac troponin does not provide equivalent prediction in men and women, with lower thresholds needed for women to provide comparable risk stratification. SUMMARY: Sex differences in cardiac troponin concentrations are not widely recognised in clinical practice and may be contributing to the under-diagnosis of myocardial infarction in women and discrepancies in patient care and outcomes

Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy

Background Adjuvant radiotherapy (RT) for left-sided breast cancer increases cardiac morbidity and mortality. For the heart, no safe radiation threshold has been established. Troponin T is a sensitive marker of myocardial damage. Our aim was to evaluate the effect of left-sided breast cancer RT on serum high sensitivity troponin T (hscTnT) levels and its association with cardiac radiation doses and echocardiographic parameters. Methods A total of 58 patients with an early stage, left-sided breast cancer or ductal carcinoma in situ (DCIS) who received adjuvant breast RT without prior chemotherapy were included in this prospective, non-randomized study. Serum samples were taken before, during and after RT. An increase of hscTnT >30 % was predefined as significant. A comprehensive 2D echocardiograph and electrocardiogram (ECG) were performed before and after RT. Dose-volume histograms (DVHs) were generated for different cardiac structures. Results The hscTnT increased during RT from baseline in 12/58 patients (21 %). Patients with increased hscTnT values (group A, N = 12) had significantly higher radiation doses for the whole heart (p = 0.02) and left ventricle (p = 0.03) than patients without hscTnT increase (group B, N = 46). For the left anterior descending artery (LAD), differences between groups A and B were found in volumes receiving 15 Gy (p = 0.03) and 20 Gy (p = 0.03) Furthermore, after RT, the interventricular septum thickened (p = 0.01), and the deceleration time was prolonged (p = 0.008) more in group A than in group B. Conclusions The increase in hscTnT level during adjuvant RT was positively associated with the cardiac radiation doses for the whole heart and LV in chemotherapy-naive breast cancer patients. Whether these acute subclinical changes increase the risk of excessive long-term cardiovascular morbidity or mortality, will be addressed in the follow-up of our patients.BioMed Central open acces

Integration of ISO15189 and external quality assurance data to assist the detection of poor laboratory performance in New South Wales

A systematic survey of the peer-reviewed literature was conducted to identify the key international themes that govern laboratory quality management. Informed by the survey results, predictive models utilising assessment data against the ISO 15189 standard, and external quality assurance programme (EQA) data, were assessed. Via PubMed, a systematic survey (SS) of the international pathology quality literature identified more than 100 articles, which were subjected to text-mining and meta-analyses via R statistical programming. Word patterns were examined for indicators of current best practice in quality assurance. Random Forest and ANCOVA models were subsequently developed with data obtained from twenty-one anonymous pathology laboratories in NSW. The SS and text-mining did not show a consistent international consensus for laboratory quality; however, approximately 15% of articles suggested root cause analysis as a means to investigate quality problems. Using the Random Forest algorithm, an integrated ISO 15189 – EQA model was developed, with results further supported by ANCOVA. The combined Random Forest – ANCOVA method succeeded in identifying EQA markers (e.g., serum potassium) that correlated with ISO 15189 audit results, providing a robust predictive model of laboratory quality monitoring superior to that proposed for root cause analyses

The Pharmacokinetics of Simplex-Tobramycin Bone Cement

We prospectively investigated a consecutive series of ten patients undergoing a cemented primary total hip replacement (THR) for osteoarthritis in order to establish the elution characteristics of Simplex-tobramycin bone cement (Howmedica, Limerick, Ireland). Specimens of blood, urine and drainage fluid were collected for 72 hours postoperatively. Very high concentrations of tobramycin were found in the drainage fluid, with mean levels at one hour of 103 mg/l, which steadily declined to 15.1 mg/l after 48 hours. The mean serum tobramycin levels reached a peak of 0.94 mg/l at three hours and declined rapidly to 0.2 mg/l by 48 hours. The mean urinary tobramycin levels peaked at 57.8 mg/l at 12 hours with a rapid decline to 12.6 mg/l by 24 hours. There was a direct correlation between the amount of tobramycin bone cement which was implanted and the amount of tobramycin systemically absorbed. Excellent local delivery was achieved with minimal systemic concentrations. Simplex-tobramycin bone cement is an efficient and safe method for the delivery of antibiotics after THR

Integration of ISO 15189 and external quality assurance data to assist the detection of poor laboratory performance in NSW, Australia

Abstract: A systematic survey (SS) of the peer-reviewed literature was conducted to identify the key international themes that govern quality management for laboratories. Informed by the survey findings, integrated models utilising assessment results against the ISO 15189 standard, and data from external quality assurance (EQA) programs, were developed to predict laboratory performance. Via the PubMed database, a SS of the international pathology quality literature identified over 100 articles, which were subsequently subjected to text mining and meta-analyses via R statistical programing. Word patterns were examined for indicators of current best practice in quality assurance. Random Forest (RF) and ANCOVA models were subsequently developed with combined ISO 15189 standard and EQA data obtained from 21 anonymous pathology laboratories in NSW. The SS and associated text mining showed no consistent international consensus, but a significant minority (15%) of articles suggested root cause analysis as a means of exploring quality problems. Using the RF algorithm, an integrated ISO 15189 external audit—EQA model was developed, with results further supported by ANCOVA. The combined RF—ANCOVA method succeeded in identifying EQA markers [e.g., serum potassium (K+)] that correlated with ISO 15189 external audit results, providing an integrated predictive model of laboratory quality more statistically robust than proposed initiatives to apply root cause analyses as a means to systematically monitor laboratory performance.Many thanks to the Quality Use of Pathology Program (QUPP), the Commonwealth Department of Health (Australia), who awarded funding to support this project (No. 4-2UJWED1)

Statistical considerations for determining high-sensitivity cardiac troponin reference intervals

The troponin 99th percentile is used as the laboratory decision point in the diagnosis of acute myocardial infarction. A recent publication has shown that the statistical treatment for outlier removal may dramatically change the calculated troponin 99th percentile. We have used our large database from the previously reported Canberra Heart Study to independently assess the effect of various methods for removing outliers on the calculated 99th percentile. We have performed the same exercise using the troponin 97.5th percentile as an exercise to assess how outlier removal may affect calculated upper reference intervals for any analyte which uses this boundary. For healthy males aged 3 × depending upon the outlier removal method chosen and for the 97.5th percentile the variation was > 50%. For women the variation in the hs-cTnI 99th percentile varied by a factor of nearly 2 ×. Qualitatively similar results were obtained forhs-cTnT. This is not simply a problem for troponin reference intervals. All analyte reference intervals have the potential to be significantly affected by the method chosen for outlier removal. To ensure that studies can be meaningfully compared, guidance on procedures for removing outliers needs to be standardized as a matter of urgency

Total intra-individual variation in sweat sodium and chloride concentrations for the diagnosis of cystic fibrosis

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