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Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%-10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented., Methods: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis., Results: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours., Conclusions: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [POC: Honoria Siemens Healthineers, Abbott Laboratories; Advisory Boards Radiometer, Psyros diagnostics, LumiraRx, Siemens Healthineers; Consultant to IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB). AHL: Honoraria Siemens Healthineers, Abbott Laboratories; Research support from Abbott Laboratories, Beckman Coulter and Siemens Healthineers. KA: Research Grants Siemens Healthineers, Roche Diagnostics; Consultancy CardiNor; Honoraria Siemens Healthineers, SNIBE; Advisory Boards Roche Diagnostics, Siemens Healthineers, SpinChip; Associate Editor Clinical Biochemistry, Chair International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers. DG: None. JS: None. KP: None. SS: Honoria Roche Diagnostics, Abbott Laboratories, SNIBE; President Serbian Society for Clinical Laboratory and Science (SCLM). HB: Grants Roche Diagnostics, Beckman Coulter. MTHL Clinical Research Training Fellowships (MR/W000598/1) from the Medical Research Council. NLM Chair Award (CH/F/21/90010), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation; Honoraria Abbott Laboratories, Siemens Healthineers, Roche Diagnostics; Advisory Boards Psyros Diagnostics, Roche Diagnostics, LumiraDx; Research Support Siemens Healthineers. PL. Chair Science Committee LabQuality Days.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Commonly used indicators of sepsis are nonspecific and insufficient for predicting the course of febrile neutropenia (FN) in hematological patients. We analyzed data from 91 adult FN patients who received intensive chemotherapy for acute myeloid leukemia or autologous stem cell transplantation. Compared to patients with non-severe sepsis, patients with severe sepsis had significantly higher serum levels of tissue inhibitor of metalloproteinases-1 on the day of first occurrence of fever (day 0: 172 vs. 112 µg/L, p = .002) and for the two following days (day 1: 219 vs. 128 µg/L, p < .001; day 2: 443 vs. 128 µg/L, p = .001), and significantly higher serum levels of matrix metalloproteinase-10 on day 1 (1975 vs. 876 ng/L, p = .001) and day 2 (2020 vs. 841 ng/L, p < .001). We conclude that the measurement of these biomarkers may be useful in predicting the severity of sepsis in FN patients.

The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), with a focus on heart failure., (© 2019 American Association for Clinical Chemistry.)

Aim: To evaluate whether the overall satisfaction, as measured by numeric rating scale (NRS), regarding rectus sheath block (RSB) analgesia is associated with the plasma glutathione peroxidase (GPX1) level. The second end-point of the study was to evaluate the differences in GPX1 levels in patients with and without RSB analgesia, with special emphasis on benign or malign disease status., Patients and Methods: Initially, 56 patients were randomized to the placebo group (n=12) and to one of three active RSB analgesia groups: single-dose (n=16), repeated-dose (n=12) and continuous infusion (n=16) groups. The plasma level of GPX1 was measured at three time points: just before, immediately after and 24 h after surgery. The overall satisfaction and an opinion on the success of the analgesic procedure were surveyed using an 11-point numeric rating scale 24 h postoperatively (NRS from 0, completely dissatisfied, to 10, fully satisfied)., Results: The placebo group and the three active groups were similar in terms of their perioperative data. The plasma level of GPX1 decreased postoperatively in all four groups. No differences were detected in the GPX1 values between the placebo and the three active groups combined preoperatively and immediately after operation. However, the patients in the single-dose group had a significantly lower median GPX1 values 24 h after surgery compared to the three other groups separately (p=0.032). The median (interquartile range) plasma level of GPX1 differed significantly between patients with benign disease and those with cancer preoperatively (18.0, 12.5-22.0 versus 10.0, 6.3-18.8 pg/ml, p=0.006) and cancer diagnosis was correlated with lower individual plasma GPX1 values (r=-0.42, p=0.004)., Conclusion: The placement of RSB analgesia does not significantly affect the level of oxidative stress biomarker GPX1 in patients with benign disease or cancer. A new finding with possible clinical relevance is that patients with cancer appeared to have a trend for lower plasma GPX1 values., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of the study was to evaluate whether the post-surgery placement of the rectus sheath block (RSB) analgesia could alter the oxidative stress response. The main hypothesis of our study was to find some correlation between patients' pain experience, numeric rating scale (NRS) and the concentration of oxidative stress marker, 8-OHdG (8-hydroxy-2'-deoxyguanosine) in patients with benign disease and cancer., Materials and Methods: Initially, 46 patients were randomized to the placebo group (n=11) and to one of the three active groups; single-dose (n=12), repeated-dose (n=12) and continuous infusion (n=11) RSB analgesia group. The plasma concentrations of the hs-C-reactive protein (CRP) and 8-OHdG were measured at three time points: just before, immediately after and 24 h after operation. The primary end-point was to compare plasma concentrations of the hs-CRP and 8-OHdG in the placebo group and in the three different RSB analgesia groups in patients with benign disease and cancer., Results: The placebo group and three active groups were similar in terms of demographic variables and the perioperative data. The patients in the continuous infusion group had a trend for lower median 8-OHdG values post-operatively than the three other study groups (p=0.147; in all patients with benign disease and cancer). The patients in the cancer group showed a trend for higher median 8-OHdG values in the repeated-dose group than the patients in the benign group (p=0.241). There was a significant inverse correlation between the individual values of the plasma hs-CRP and 8-OHdG in patients with benign disease and cancer (r=-0.40, p=0.02). However, there was no significant correlation between the individual values of the NRS score and 8-OHdG post-surgery in patients with benign disease and cancer., Conclusion: The results suggest that the placement of RSB analgesia does not significantly alter the oxidative stress marker 8-OHdG concentrations in patients with benign disease or cancer patients. A new finding with possible clinical relevance is a significant inverse correlation between the individual plasma values of the hs-CRP and 8-OHdG in patients with benign disease and cancer., (Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)

Neutropenic sepsis is a common clinical problem in hematological patients receiving intensive chemotherapy. Complications will develop in a minority of these patients. Biomarkers can be used for the recognition of infection as well as to estimate its severity and risk of complications and also to assess treatment response. Experience gained from other patient groups or sepsis patients treated in intensive care units cannot be directly extrapolated to hematological patients. Numerous biomarkers of infections have been investigated in hematological patients, but no optimal marker has been found. C-reactive protein is still the most commonly used biomarker in hematological patients, but procalcitonin may be a real challenger, although more studies are still needed.

We compared biomarkers and their changes as predictors for bacteremia and severe sepsis during neutropenic fever after intensive chemotherapy in hematological patients. Serum C-reactive protein (CRP), semi-quantative procalcitonin, aminoterminal pro-brain natriuretic peptide (NT-proBNP), cortisol, lactate, plasma antithrombin and fibrinogen were measured daily from day 0 to day 3/day 4 in 89 neutropenic fever episodes of 65 hematological patients. The best predictors for bacteremia and gram-negative bacteremia were procalcitonin and its change, with odds ratios (ORs) and 95% confidence intervals of 2.63 (1.56-4.44) and 3.20 (1.77-5.80) for bacteremia and 4.14 (2.00-8.58) and 5.04 (2.18-11.63) for gram-negative bacteremia, respectively. For severe sepsis, the best predictors were CRP and fibrinogen, with ORs of 1.94 (1.07-3.52) and 1.92 (1.05-3.54). Factor analysis provided two predictive factors: procalcitonin-NT-proBNP-antithrombin factor predicted gram-negative bacteremia and CRP-fibrinogen predicted severe sepsis. Applying a combination of markers reflecting different aspects of infection might improve the recognition of risk for complications in patients with neutropenic fever.

Objective: To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever., Methods: A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4., Results: Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively., Conclusions: An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background/Aim: We aimed to analyze the diagnostic value of total tau (T- tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. Patients and Methods: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8±50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. Results: T-tau was higher in patients with stroke [1.0 pg/ml (IQR=0.3-2.2)] than with TIA [0.5 pg/ml (IQR=0.2-1.0), p=0.02]. The levels of S100B were also increased in stroke [0.082 μg/l (IQR=0.049-0.157)] patients compared to TIA patients [0.045 μg/l (IQR=0.03-0.073), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 μg/l (IQR=9.30-16.14)] compared to those with TIA [10.96 μg/l (IQR=7.98-15.33), p=0.30] were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). Conclusion: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the levels, kinetics, and prognostic value of growth differentiation factor 15 (GDF-15) in cardiogenic shock (CS).Methods and Results: Levels of GDF-15 were determined in serial plasma samples (0-120 h) from 177 CS patients in the CardShock study. Kinetics of GDF-15, its association with 90-day mortality, and incremental value for risk stratification were assessed. The median GDF-150h level was 9647 ng/L (IQR 4500-19,270 ng/L) and levels above median were significantly associated with acidosis, hyperlactatemia, renal dysfunction, and higher 90-day mortality (56% vs 28%, P < .001). Serial sampling showed that non-survivors had significantly higher GDF-15 levels at all time points (P < .001 for all). Furthermore, non-survivors displayed increasing and survivors declining GDF-15 levels during the first days in CS. Higher levels of GDF-15 were independently associated with mortality. A GDF-1512h cutoff >7000 ng/L was identified as a strong predictor of death (OR 5.0; 95% CI 1.9-3.8, P = .002). Adding GDF-1512h >7000 ng/L to the CardShock risk score improved discrimination and risk stratification for 90-day mortality.Conclusions: GDF-15 levels are highly elevated in CS and associated with markers of systemic hypoperfusion and end-organ dysfunction. GDF-15 helps to discriminate survivors from non-survivors very early in CS. [ABSTRACT FROM AUTHOR]

Background: The aim of this survey was to investigate how well heart failure (HF) guidelines for use of natriuretic peptides (NPs) have been implemented in laboratory practice in Europe and North America. Methods: In 2013 and 2014, a web-based questionnaire was distributed via North American and European biochemical societies. Questions covered assay performed, reason for method choice, decision limits for HF, and laboratory accreditation status. Results: There were 442 European Union and 91 North American participating laboratories with response rates of 50% and 64% from major or university hospitals, respectively. NP measurements were offered in 67% of European Union and 58% of North American respondents. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was most widely used in Europe (68%) and B-type natriuretic peptide (BNP) was more commonly used (58%) in North America. The most frequent reason for use of a specific assay was the availability of instruments that measure either NT-proBNP (51%) or BNP (67%). For diagnosis of acute HF, NT-proBNP decision limits were diverse; age-dependent limits based on the 2012 European Society of Cardiology (ESC) recommendations were used in only 17% of European sites and 26% of North American sites. For BNP, the guideline-recommended acute HF decision limit of 100 ng/L was better adhered to in Europe (48%) and North America (57%). Surprisingly, similar decision limits were stated for acute and chronic HF by >50% of respondents. Conclusions: NP measurement for HF diagnosis was available in >50% of responding laboratories. However, guideline recommended cutoff values for both acute and chronic HF were still implemented in <30% of participating medical centers. [ABSTRACT FROM AUTHOR]

Background and Objective: Based on earlier literature, etoricoxib may have a delayed analgesic effect in postoperative setting when analgesic efficacy of nonselective nonsteroidal anti-inflammatory drug dexketoprofen is rapid. This may be caused by slow penetration of etoricoxib into the central nervous system (CNS). Therefore we decided to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics and pharmacodynamics of dexketoprofen and etoricoxib in patients with hip arthroplasty. Methods: A total of 24 patients, scheduled for an elective primary hip arthroplasty were enrolled. After surgery, 12 subjects were randomized to received a single intravenous dose of dexketoprofen, and 12 subjects were given oral etoricoxib. Paired blood and CSF samples were taken up to 24 h for measurement of drug concentrations, interleukin (IL)-6, IL-1ra and blood for interleukin 10. Results: In CSF the highest measured concentration ( C ) of dexketoprofen was 4.0 (median) ng/mL (minimum-maximum 1.9-13.9) and time to the highest concentration ( t ) 3 h (2-5), and for etoricoxib C 73 ng/mL (36-127) and t 5 h (1-24), respectively. Opioid consumption during the first 24 postoperative hours was similar in the two groups. Dexketoprofen and etoricoxib had a similar effect on the postoperative inflammatory response. No significant differences considering pain relief or adverse events were found between the two groups. Conclusion: Dexketoprofen and etoricoxib entered the CNS readily, already at 30 min after administration dexketoprofen was detected in the CSF in most subjects and etoricoxib after 60 min. A single dose of dexketoprofen and etoricoxib provided a similar anti-inflammatory and analgesic response after major orthopaedic surgery. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which the authors examine the use of a soluble urokinase-type plasminogen activator receptor as a biomarker to diagnose patients suffering from infectious complications and neutropenic fever resulting from intense chemotherapy for hematological malignancies.

Background: Natriuretic peptides (NP) are well-established markers of heart failure (HF). During the past 5 years, analytical and clinical recommendations for measurement of these biomarkers have been published in guidelines. The aim of this follow-up survey was to investigate how well these guidelines for measurement of NP have been implemented in laboratory practice in Europe. Methods: Member societies of the European Federation of Clinical Chemistry and Laboratory Medicine were invited in 2009 to participate in a web-based audit questionnaire. The questionnaire requested information on type of tests performed, decision limits for HF, turn-around time and frequency of testing. Results: There was a moderate increase (12%) of laboratories measuring NP compared to the initial survey in 2006. The most frequently used HF decision limits for B-type NP (BNP) and N-terminal BNP (NT-proBNP) were, respectively, 100 ng/L and 125 ng/L, derived from the package inserts in 55%. Fifty laboratories used a second decision limit. Age or gender dependent decision limits were applied in 10% (8.5% in 2006). The vast majority of laboratories (80%) did not have any criteria regarding frequency of testing, compared to 33% in 2006. Conclusions: The implementation of NP measurement for HF management was a slow process between 2006 and 2009 at a time when guidelines had just been established. The decision limits were derived from package insert information and literature. There was great uncertainty concerning frequency of testing which may reflect the debate about the biological variability which was not published for most of the assays in 2009. [ABSTRACT FROM AUTHOR]

Background: Replacing SFAs with vegetable PUFAs has cardio- metabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory. Objective: We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders. Design: We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined. Results: A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between- group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycérides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged. Conclusions: Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs. This trial was registered at clinicaltrials.gov as NCT01038102. [ABSTRACT FROM AUTHOR]

Background: The performance of first trimester biochemical screening was compared at different pregnancy weeks and maternal ages during 2002-2008 in a screened population of 76,949 women. Methods: The detection rates, as well as the median multiples of a median (MOMs) of free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), were compared between completed gestational weeks 8-13 and between different maternal ages separated into 5-year groupings. Results: The number of singleton Down syndrome pregnancies was 221. The median age of the screened women was 30 years and the proportion of women aged ≥35 years 16.9%. The median age of the women with a Down syndrome pregnancy was 37 years. In women aged <35 years, the biochemical markers provided a detection rate of only 38.6%, whereas in women aged ≥35 years, the biochemical markers detected 82.7% of cases (p<0.01). Conclusions: Biochemical screening works best amongst women aged ≥35 years. For younger mothers aged <35 years, combined screening should be the method of choice. [ABSTRACT FROM AUTHOR]

Aim: There is a need for markers of Th1 and Th2 imbalance in diseases such as asthma. CD30 is an activation marker of Th2 cells, and importance of Th1 marker CD26 was recently found in adult asthma. We studied whether serum-soluble CD30 (sCD30) or serum-soluble CD26 (sCD26) could support early diagnosis of asthma in children at school age. Methods: sCD26 and sCD30 were measured in 34 children with clinically confirmed asthma, 31 with possible asthma and in 147 controls. In addition, the associations of flow volume spirometry, methacholine inhalation challenge and free running test results with serum sCD26 or sCD30 were analysed. Results: Serum sCD30 was significantly higher in children with confirmed asthma (mean 91.5 IU/mL, SD 23.0) than in the controls (78.8 IU/mL, 25.9; p = 0.042). No significant differences were found in serum sCD26 levels between the groups. There was a negative correlation of mean mid expiratory flow values with serum sCD26 (r = −0.22, p = 0.0018). Neither methacholine inhalation challenge nor free running test results were associated with serum sCD26 or sCD30. Conclusion: Serum sCD30 was higher in children with asthma. However, marked overlap in serum sCD30 between asthmatic and healthy children limits the usefulness of sCD30 as a diagnostic marker of asthma. [ABSTRACT FROM AUTHOR]

Objectives . To investigate the diagnostic approach in Nordic hospitals receiving patients suspected of acute myocardial infarction (MI), especially focusing on implementation of the recently proposed criteria by the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) for the definition of MI. Design . A survey with questionnaires of the diagnostic approach was conducted among all relevant departments (220) in the Nordic countries. Results . Seventy-six percent (167) of hospitals responded. Troponins I and T (TnI and TnT) and creatinine kinase monobasic fraction (mass concentration) (CKMB mass ) covered 93 and 65% of hospitals, respectively. Of troponin users, 34% indicated use of TnI vs 66% using TnT. Sporadic use of AST, CK, LD and myoglobin was reported. There was a tendency to lower cut-off levels in Sweden and Finland. Among troponin assays, there was considerable heterogeneity regarding cut-off levels. Conclusions . The Nordic countries are approaching ESC/ACC consensus on cardiac markers. Compared with previous national surveys (1995–1999), there is a shift towards the use of troponins. However, differences in cut-off levels of troponin emphasize the need for harmonization of assays. [ABSTRACT FROM AUTHOR]

The strength of the association between cardiac biomarker release and prognosis is uncertain. We performed a systematic literature search to find articles regarding these markers and death after coronary surgical interventions, and evaluated the results with meta-analytic methods. We found 23 articles concerning 29,483 patients that reported the MB fraction of creatine kinase (CK-MB) and troponin T and I. Heterogeneity of existing studies prevented the pooling of the results of troponin studies. The pooled data of the CK-MB studies suggest that after coronary artery bypass grafting, CK-MB release of more than five to eight times the upper limit of the reference range is associated with an increased risk of death during the next 40 months. [Copyright &y& Elsevier]

Background. Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies. Methods. Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38° and on the next morning. Results. Altogether, 90 differential molecular features were shown to explain the differences between patients with complicated (bacteremia, severe sepsis, or fatal outcome) and noncomplicated courses of febrile neutropenia. The most differential compounds were an androgen hormone, citrulline, and phosphatidylethanolamine PE(18:0/20:4). The clinical relevance of the findings was evaluated by comparing them with conventional biomarkers like C-reactive protein and procalcitonin. Conclusion. These results hold promise to find out novel biomarkers for febrile neutropenia, including citrulline. Furthermore, androgen metabolism merits further studies. [ABSTRACT FROM AUTHOR]

Objectives: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock.Design: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality.Setting: Nine tertiary care university hospitals.Patients: Patients with cardiogenic shock caused by acute coronary syndrome (n=145).Interventions: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement.Measurements and Main Results: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients.Conclusions: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Copeptin, the surrogate marker of arginine vasopressin (AVP), has been suggested to be a useful biomarker in monitoring sepsis reflecting hemodynamic imbalance and stress state. This prospective study conducted at a hematology ward in a Finnish University Hospital aimed to investigate whether plasma copeptin predicts the development of complicated course of neutropenic fever (bacteremia or need for treatment at intensive care unit) in 100 hematological patients experiencing their first neutropenic fever episode after intensive chemotherapy for hematological malignancy. Contrary to study presumptions, not elevated copeptin but the lack of a proper initial increase of plasma copeptin (<0.02ng/mL from day 0 to day 1) predicted blood culture positive sepsis (p =0.023) and gram-negative bacteremia (p =0.045). No correlation was observed with plasma sodium, blood pressure or evaluated osmolality. Plasma copeptin correlated inversely with the same day pentraxin 3 on day 0–day 2 (all p-values <0.001) and with C-reactive protein on day 1 (p =0.015). In conclusion, copeptin did not correlate with disease severity, but the lack of a proper initial increase was associated with bacteremic complications of febrile neutropenia in hematological patients. The findings suggest the possibility of central dysregulation of AVP release and do not support the use of copeptin as a biomarker of septic complications in this patient group. [Copyright &y& Elsevier]

Abstract: Objective: To investigate links between first trimester Down''s syndrome screening markers and adverse pregnancy outcomes; preeclampsia (PE), small for gestational age (SGA), preterm delivery (PD) and placental abruption (PA) in spontaneous, chromosomally normal pregnancies. Study design: Cohort study in a university hospital. Data during pregnancy were routinely collected from a total study population of 2844 pregnant women between 2005 and 2007. Four study groups were pregnancies with PE (N =175), PA (N =17), PD (N =213) and SGA (N =275) plus a reference group with normal outcome (N =2164). The median MOMs of maternal serum concentrations of pregnancy associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) were compared using two-tailed pooled t-tests, continuous variables were compared using Student''s two-way t-tests, and Chi-square tests were used to analyse dichotomous variables. Fisher''s exact test was used when there were fewer than five units in any of the classes. Results: The median MOM of maternal serum PAPP-A was significantly lower in women with PE, PD and SGA (0.79, 0.80 and 0.79 MOM, respectively) than in the reference group (0.99 MOM) (p <0.01). The median MOM of maternal serum fβ-hCG was also significantly lower in the SGA group (0.90 MOM) and in the PE and PD groups (0.86 and 0.92 MOM) than in the reference group (0.99 MOM, p =0.02). There was no detectable difference between the biochemical markers in the PA group and the reference group. No statistical difference was found between NT MOMs in the reference and study groups. Conclusion: The concentrations of first trimester screening (FTS) serum markers were lower in pregnancies where PE, PD and SGA occurred. In the latter two cases, there was an inverse association between incidence and PAPP-A and fβ-hCG values. However, the development of PA during pregnancy could not be predicted from biochemical marker concentrations. The mechanism behind PA is probably less dependent on the placenta than on the decidua. [Copyright &y& Elsevier]

Abstract: Background: We compared the early diagnostic and prognostic performance of a highly sensitive cardiac troponin I (cTnI) assay with heart-type fatty acid binding protein (H-FABP), in the early hours of acute coronary syndrome. Methods: Serum samples of 293 patients were studied using the Abbott Architect cTnI assay and the H-FABP assay. Special attention was paid to the diagnostic and prognostic value of admission blood samples taken <24 h after symptom onset. The prognostic endpoint was total mortality and reinfarction at 6 months. Results: To detect forthcoming myocardial injury, admission samples gave receiver operating curve (ROC) areas (AUC) of 0.908 for cTnI and 0.855 for H-FABP (p =0.068) when the delay from symptom onset was <6 h (60.4% of all patients). When the delay was 6–24 h, the corresponding AUC values were 0.995 for cTnI and 0.849 for H-FABP (p =0.002). In multivariate analysis cTnI but not H-FABP predicted adverse events in all 293 patients (RR 3.02, 95% CI 1.62–5.63) and in those with delays <6 h (RR 2.92, 95% CI 1.47–5.81). Conclusion: In the era of highly sensitive cTnI assays, H-FABP appears to give no additional information even in patients who present within the first 6 h after acute MI. [Copyright &y& Elsevier]