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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. [ABSTRACT FROM AUTHOR]

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]

This article discusses the use of procalcitonin (PCT) in neonatology and pediatrics in Finland between 2016 and 2021. The study collected data on PCT use in Finnish hospitals, evaluated the impact of the COVID-19 pandemic on PCT use, and conducted an online survey to gather physicians' perceptions of PCT. The findings show that PCT use for neonates was low in Finland, and there were significant differences in PCT use among the five tertiary care hospitals. The study also found that PCT use decreased during the COVID-19 pandemic, particularly in younger age groups. The survey revealed that some physicians use PCT for decision-making, but others cited a lack of knowledge about its strengths and limitations. Overall, the study suggests that PCT use is not commonly favored by neonatologists and pediatricians in Finland, despite research indicating its potential as a diagnostic tool. [Extracted from the article]

Paraproteins are a potential source of error for electrolyte analyses. The exclusion effect itself causes a discrepancy between direct and indirect ion selective electrode assays (dISE and iISE, respectively). We tested the applicability of different pretreatment methods and the difference of dISE and iISE with paraprotein-rich samples. We analysed chloride (Cl-), potassium (K+), and sodium (Na+) on 46 samples with paraproteins up to 73 g/L. We compared pretreatment methods of preheating, precipitation, and filtration to the native sample. All induced a statistically significant difference (p-value <0.05). Clinically significant difference was induced by precipitation for all analytes, and filtration for Cl- and Na+, but for none by preheating. The difference in electrolyte measurements with either dISE or iISE on native samples was explained by total protein concentration (TP). There was a statistically significant difference in all electrolyte measurements. On average, there was a clinically significant difference in Na + but not in Cl- and K + measurements. Paraprotein concentration (PP) or heavy chain class did not induce a statistically significant effect. The regression analysis and comparison to the theoretical exclusion effect supported the conclusion that TP is the only explanatory factor in the difference between dISE and iISE. We conclude that preheating is a suitable pretreatment method for all the studied analytes. Precipitation is not valid for any of them, and filtration can be considered only for K+. Because the difference between dISE and iISE was explained by the exclusion effect caused by TP, dISE is the more suitable method to analyse paraprotein-rich samples. [ABSTRACT FROM AUTHOR]

The study aim was to determine the benefit of the measurement of serum caspase-cleaved cytokeratin-18 (CK-18) fragment as a prognostic marker of febrile neutropenia (FN) in hematological patients. The study population consisted of 86 consecutive patients with FN who received intensive chemotherapy for hematological malignancy at the adult hematology ward of Kuopio University Hospital. Twenty-three patients (27%) had acute myeloid leukemia, and 63 patients (73%) were autologous stem cell transplant recipients. Serum caspase-cleaved CK-18 fragment M30, C-reactive protein (CRP) and procalcitonin (PCT) were measured at the onset of FN (d0), on day 1 (d1), and on day 2 (d2). Eight patients (9%) developed severe sepsis, including three patients with septic shock. Eighteen patients (21%) had a blood culture-positive infection. Serum CK-18 fragment peaked on the first day after fever onset in patients with severe sepsis. Higher CK-18 level was associated with severe sepsis, intensive care unit treatment, and fatal outcome, but not with blood culture positivity. In ROC curve analysis, d1 serum CK-18 fragment predicted severe sepsis with an area under the curve (AUC) of 0.767, CRP with an AUC of 0.764, and PCT with an AUC of 0.731. On d2, the best predictive capacity was observed for CRP with an AUC of 0.832. The optimal cutoff of caspase-cleaved CK-18 fragment M30 for predicting severe sepsis was 205 U/L on d1. In hematological patients, serum CK-18 fragment was found to be a potential prognostic marker of severe sepsis at early stages of FN. [ABSTRACT FROM AUTHOR]

Background: Previously, several indexes based on a large number of clinical and laboratory tests to predict mortality and frailty have been produced. However, there is still a need for an easily applicable screening tool for every-day clinical practice.Methods: A prospective study with 10- and 18-year follow-ups. Fourteen common laboratory tests were combined to an index. Cox regression model was used to analyse the association of the laboratory index with institutionalization and mortality.Results: The mean age of the participants (n = 1153) was 73.6 (SD 6.8, range 64.0-100.0) years. Altogether, 151 (14.8%) and 305 (29.9%) subjects were institutionalized and 422 (36.6%) and 806 (69.9%) subjects deceased during the 10- and 18-year follow-ups, respectively. Higher LI (laboratory index) scores predicted increased mortality. Mortality rates increased as LI scores increased both in unadjusted and in age- and gender-adjusted models during both follow-ups. The LI did not significantly predict institutionalization either during the 10- or 18-year follow-ups.Conclusions: A practical index based on routine laboratory tests can be used to predict mortality among older people. An LI could be automatically counted from routine laboratory results and thus an easily applicable screening instrument in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p < 0.001) and 5.2 (95% CI 2.8–9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. Trial registration: NCT01374867 at www.clinicaltrials.gov, registered 16 Jun 2011—retrospectively registered [ABSTRACT FROM AUTHOR]

Objectives: To evaluate quick Sequential Organ Failure Assessment (qSOFA) score during febrile neutropenia (FN) in adult patients receiving intensive chemotherapy for acute myeloid leukemia (AML). Methods: qSOFA score, as well as the association of qSOFA score with ICU admission, infectious mortality, blood culture findings, and C‐reactive protein (CRP) measurements during FN were assessed among 125 adult AML patients with 355 FN periods receiving intensive chemotherapy in a tertiary care hospital from November 2006 to December 2018. Results: The multivariate model for qSOFA score ≥ 2 included CRP ≥ 150 mg/L on d0‐2 [OR 2.9 (95% CI 1.1‐7.3), P =.026], Gram‐negative bacteremia [OR 2.7 (95% CI 1.1‐6.9), P =.034], and treatment according to AML‐2003 vs more recent protocols [OR 2.7 (95% CI 1.0‐7.4), P =.047]. Age or gender did not gain significance in the model. qSOFA score ≥ 2 was associated with ICU treatment and infectious mortality during FN with sensitivity and specificity of 0.700 and 0.979, and 1.000 and 0.971, respectively. Conclusion: qSOFA offers a useful tool to evaluate the risk of serious complications in AML patients during FN. [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]

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total – HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin is a biomarker that can be used to diagnose bacterial infection and monitor treatment. Clinical practice guidelines are evidence-based recommendations by experts that aim to aid decision-making. In this systematic review, we searched for clinical practice guidelines and evaluated recommendations given regarding use of procalcitonin. Methods: Four biomedical databases (PubMed, Scopus, Cochrane Database and Web of Science) and various national medical sites were searched for clinical practice guidelines. Guidelines that mentioned procalcitonin were included in the review. Results: Seventeen guidelines were included. The earliest were published in 2009 and the latest in 2018. A majority (12/17) recommended use of procalcitonin or stated that it can be useful. One national guideline did not recommend procalcitonin, stating that there is no need for any biomarkers in diagnostics of community-acquired pneumonia in adults. Four guidelines stated no evidence to recommend or not recommend procalcitonin use. Thirteen of the guidelines commented on other concomitant or alternate biomarkers, mainly C-reactive protein. Five guidelines suggested decision limits for procalcitonin. None took a stand on how often procalcitonin should be analysed, and if it should be used as a single or as multiple measurements. Conclusions: One international and 11 national clinical practice guidelines endorse the use of procalcitonin in differential diagnosis of bacterial infections and/or to monitor antibiotic therapy. However, the evidence for or against the use of procalcitonin is weak. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown. Materials and methods: P-Alb was measured from serial blood samples in 178 patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality. Results: Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 [95% CI 1.5–4.1] per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 [95% CI 1.1–3.8], IABP-SHOCK II score adjusted odds ratio 2.5 [95%CI 1.2–5.0]) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 [95%CI 1.2–7.1]). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome. Conclusions: Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock. Trial registration: at ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation. [ABSTRACT FROM AUTHOR]

Aims: The role of microRNAs has not been studied in cardiogenic shock. We examined the potential role of miR‐423‐5p level to predict mortality and associations of miR‐423‐5p with prognostic markers in cardiogenic shock. Methods and results: We conducted a prospective multinational observational study enrolling consecutive cardiogenic shock patients. Blood samples were available for 179 patients at baseline to determine levels of miR‐423‐5p and other biomarkers. Patients were treated according to local practice. Main outcome was 90 day all‐cause mortality. Median miR‐423‐5p level was significantly higher in 90 day non‐survivors [median 0.008 arbitrary units (AU) (interquartile range 0.003–0.017) vs. 0.004 AU (0.002–0.009), P = 0.003]. miR‐423‐5p level above median was associated with higher lactate (median 3.7 vs. 2.4 mmol/L, P = 0.001) and alanine aminotransferase levels (median 68 vs. 35 IU/L, P < 0.001) as well as lower cardiac index (1.8 vs. 2.4, P = 0.04) and estimated glomerular filtration rate (56 vs. 70 mL/min/1.73 m2, P = 0.002). In Cox regression analysis, miR‐423‐5p level above median was associated with 90 day all‐cause mortality independently of established risk factors of cardiogenic shock [adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), P = 0.01]. Conclusions: In cardiogenic shock patients, above median level of miR‐423‐5p at baseline is associated with markers of hypoperfusion and seems to independently predict 90 day all‐cause mortality. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-associated plasma protein A (PAPP-A), especially in its noncomplexed form (fPAPP-A), is linked to vulnerable atherosclerotic plaques and risk of cardiac events. An assay for sensitive detection of fPAPP-A has been lacking. Our aim was to develop and validate a direct fPAPP-A assay to meet this need. Methods: Monoclonal antibodies binding exclusively fPAPP-A were produced by immunizing mice with recombinant PAPP-A. In the optimized immunoassay, we used an fPAPP-A--specific capture antibody together with a lanthanide-chelate--labeled monoclonal antibody recognizing all PAPP-A forms. The assay was evaluated with CLSI guidelines and compared to a 2-assay subtractive fPAPP-A approach. Clinical performance was assessed with acute coronary syndrome patients. Results: The limits of detection and quantitation were 0.4 mIU/L and 1.3 mIU/L, respectively, and the assay was linear up to 1000 mIU/L (R2 = 0.999). Both serum and heparin plasma were suitable matrices, and the complexed form of PAPP-A caused no significant interference. Correlation between the developed assay and the 2-assay approach was fair (Pearson's r = 0.819). Median concentration in healthy individuals was 1.0 mIU/L. fPAPP-A concentration was higher in patients who had myocardial infarction or died during the 1-year follow-up period than in those who did not (1.13 mIU/L vs 0.82 mIU/L, P = 0.008, model adjusted with age and sex). fPAPP-A measured with this direct assay predicted this end point as well as (follow-up 1 year) or better (30 days) than the 2-assay fPAPP-A alone or in combination with cTnI. Conclusions: The new assay enables sensitive and reliable measurement of low cardiac-related fPAPP-A concentrations from blood samples. [ABSTRACT FROM AUTHOR]

Objective: The study aim was to compare the performance of interleukin‐1 receptor antagonist (IL‐1Ra) to C‐reactive protein (CRP) and procalcitonin (PCT) in early prediction of the clinical course of febrile neutropenia. Methods: The study population consisted of 86 consecutive patients with febrile neutropenia who received intensive chemotherapy for haematological malignancy between November 2009 and November 2012 at the adult haematology ward of Kuopio University Hospital. Twenty‐three (27%) patients had acute myeloid leukaemia and 63 (73%) patients were autologous stem cell transplant recipients. IL‐1Ra, CRP and procalcitonin were measured at the onset of fever (d0), on day 1 (d1) and on day 2 (d2). Results: Eight patients developed severe sepsis, including three patients with septic shock. Eighteen patients had bacteraemia. After the onset of febrile neutropenia Youden´s indices (with their 95% confidence intervals) to identify severe sepsis were for IL‐1Ra on d0 0.57 (0.20‐0.71) and on d1 0.65 (0.28‐0.78), for CRP on d0 0.41 (0.04‐0.61) and on d1 0.47 (0.11‐0.67) and for PCT on d0 0.39 (0.05‐0.66) and on d1 0.52 (0.18‐0.76). Conclusions: In haematological patients, IL‐1Ra has a comparable capacity with CRP and PCT to predict severe sepsis at the early stages of febrile neutropenia. [ABSTRACT FROM AUTHOR]

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Objectives:The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke. Subjects and methods:First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women. Results:PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6–48.5) pg/ml,p = .001] and reduced sEng concentration [5.0 (4.6–5.6) ng/ml,p = .047] compared to PE non-smokers [30.0 (28.1–32.1) pg/ml and 6.1 (5.9–6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy. Conclusions: The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker.Key messagesSmoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies.Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker. [ABSTRACT FROM PUBLISHER]

Aims: A chronically elevated level of von Willebrand factor (vWF) is a common finding in patients with cardiovascular diseases. Obesity is a well-recognized risk factor for thrombotic cardiovascular complications including ischemic stroke, and it has been linked with increased plasma vWF. We evaluated whether elevated plasma levels of vWF associate with areas of visceral (VAT), pericardial (PAT), and subcutaneous adipose tissue (SAT) compartments in patients with acute/subacute stroke. Methods and results: A total of 69 patients with stroke of suspected cardiogenic etiology were examined. The plasma level of vWF antigen (vWF-ag) was measured both in the acute phase and in the chronic phase three months after stroke. The areas of VAT and/or PAT were assessed with computed tomography. As expected, in stroke patients, the levels of plasma vWF-ag were significantly higher than in the national reference population both in the acute and in the chronic phase. The level of vWF-ag in the chronic phase correlated with the amounts of VAT and PAT, but not with subcutaneous adipose tissue. Conclusions: These results agree with previous observations of the chronic inflammation/prothrombotic tendency in patients with cerebrovascular disease. Future studies should seek to clarify the role of visceral type adipose tissue in the pathophysiology of ischemic stroke. [ABSTRACT FROM AUTHOR]

Asymmetric dimethylarginine (ADMA) has been recognized as an independent prognostic factor for sepsis mortality in intensive care units. No data are available on kinetics or prognostic value of ADMA in hematological patients. We evaluated the ability of ADMA to act as a predictor for complicated course of febrile neutropenia, defined as bacteremia and/or septic shock in adult hematological patients receiving intensive chemotherapy. This prospective study included 87 adult hematological patients with febrile neutropenia after an intensive chemotherapy for acute myeloid leukemia (AML) or after an autologous stem cell transplantation (ASCT). Plasma ADMA and serum C-reactive protein (CRP) levels were measured from the onset of fever (d0) and for 2 days (d1–d2) thereafter. The levels of ADMA were stable or had only minimal changes during the study period. There was no difference between the levels at any time-point in patients having complicated course compared to those without it. On the other hand, CRP levels were significantly higher on d1 (p = 0.016) in patients with bacteremia and/or septic shock than in those without. ADMA was not able to differentiate hematological patients with a complicated course from those without complications. Elevated ADMA levels are probably associated with organ dysfunction, which is rare in this group of patients, of whom about 95% can be successfully managed at the hematology ward. [ABSTRACT FROM PUBLISHER]

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: The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods: CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results: Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points ( P < 0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal (≤2 mmol/L) in most patients regardless of later outcome with lower prognostic value. By contrast, bio-ADM showed increasing prognostic value from 48 h and beyond (AUC 0.71 at 48 h and 0.80 at 5-10 days). Serial measurements of either bio-ADM or lactate were independent of and provided added value to CardShock risk score ( P < 0.001 for both). Ninety-day mortality was more than double higher in patients with high levels of bio-ADM (>55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions: Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS. Study identifier of CardShock study NCT01374867 at clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Objective:The aim of the study was to evaluate the role of 8-OHdG (8-hydroxy-2′-deoxyguanosine) detecting oxidative stress response following cholecystectomy in a randomised multicentre study of patients with minilaparotomy cholecystectomy (MC) versus laparoscopic cholecystectomy (LC). Methods:Initially, 106 patients with non-complicated symptomatic gallstone disease were randomised into MC (n = 56) or LC (n = 50) groups. Plasma levels of the oxidative stress marker 8-OHdG measured at three time points; before (PRE), immediately after (POP1) and 6 h after operation (POP2). Results:The demographic variables and the surgical data were similar in the study groups. The plasma oxidative stress marker 8-OHdG concentrations following surgery in the MC versus LC patients were quite similar. There was no significant correlation between the individual values of the11-point numeric rating pain scale (NRS) versus the plasma 8-OHdG post-operatively in the MC and LC patients. However, there was a statistically significant correlation between the individual values of the plasma 8-OHdG (PRE)versusIL-10 (PRE) for the MC and LC patients (r = 0.214,p = 0.037). There was also a statistically significant correlation between the individual values of the plasma 8-OHdG (POP2) versus IL-1β (POP2) for the MC and LC patients (r = 0.25,p = 0.01). Conclusion:Our results suggest that the oxidative stress marker 8-OHdG concentrations following surgery in MC versus LC patients were quite similar. A new finding with possible clinical relevance is a correlation between the individual plasma values of the 8-OHdG versus anti-inflammatory interleukin IL-10 and 8-OHdG versus IL-1β (proinflammatory) in the MC and LC patients suggesting that inflammation and oxidative stress are related. [ABSTRACT FROM AUTHOR]

Aims To critically evaluate the clinical implications of the use of non-fasting rather than fasting lipid profiles and to provide guidance for the laboratory reporting of abnormal non-fasting or fasting lipid profiles. Methods and results Extensive observational data, in which random non-fasting lipid profiles have been compared with those determined under fasting conditions, indicate that the maximal mean changes at 1-6 h after habitual meals are not clinically significant [+0.3 mmol/L (26 mg/dL) for triglycerides; 20.2 mmol/L (8 mg/dL) for total cholesterol; 20.2 mmol/L (8 mg/dL) for LDL cholesterol; +0.2 mmol/L (8 mg/dL) for calculated remnant cholesterol; 20.2 mmol/L (8 mg/dL) for calculated non-HDL cholesterol]; concentrations of HDL cholesterol, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) are not affected by fasting/non-fasting status. In addition, non-fasting and fasting concentrations vary similarly over time and are comparable in the prediction of cardiovascular disease. To improve patient compliance with lipid testing, we therefore recommend the routine use of non-fasting lipid profiles, while fasting sampling may be considered when non-fasting triglycerides .5 mmol/L (440 mg/dL). For non-fasting samples, laboratory reports should flag abnormal concentrations as triglycerides ≥2 mmol/L (175 mg/dL), total cholesterol ≥5 mmol/L (190 mg/dL), LDL cholesterol ≥3 mmol/L (115 mg/dL), calculated remnant cholesterol ≥0.9 mmol/L (35 mg/dL), calculated non-HDL cholesterol ≥3.9 mmol/L (150 mg/dL), HDL cholesterol ≤1 mmol/L (40 mg/dL), apolipoprotein A1 ≤1.25 g/L (125 mg/dL), apolipoprotein B ≥1.0 g/L (100 mg/dL), and lipoprotein(a) ≥50 mg/dL (80th percentile); for fasting samples, abnormal concentrations correspond to triglycerides ≥1.7 mmol/L (150 mg/dL). Life-threatening concentrations require separate referral when triglycerides .10 mmol/L (880 mg/dL) for the risk of pancreatitis, LDL cholesterol .13 mmol/L (500 mg/dL) for homozygous familial hypercholesterolaemia, LDL cholesterol .5 mmol/L (190 mg/dL) for heterozygous familial hypercholesterolaemia, and lipoprotein(a) .150 mg/dL (99th percentile) for very high cardiovascular risk. Conclusion We recommend that non-fasting blood samples be routinely used for the assessment of plasma lipid profiles. Laboratory reports should flag abnormal values on the basis of desirable concentration cut-points. Non-fasting and fasting measurements should be complementary but not mutually exclusive. [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]

ObjectiveThe aim of the study was to evaluate the inflammatory response to surgical trauma in minilaparotomy cholecystectomy (MC) compared to laparoscopic cholecystectomy (LC). Assessment of inflammatory response to surgical trauma in MC has not been addressed properly. Therefore, we investigated five interleukins (IL) and C-reactive protein (CRP) in MC versus LC group in a prospective randomised trial.MethodsInitially, 106 patients with non-complicated symptomatic gallstone disease were randomised into MC (n = 56) or LC (n = 50) groups. Plasma levels of five interleukins (IL-1β, IL-1ra, IL-6, IL-8, IL-10) and hs-CRP were measured at three time points; before operation (PRE), immediately after operation (POP1) and six hours after operation (POP2). The primary end-point of the study was to compare the plasma levels of five interleukins and CRP in LC versus MC group.ResultsThe demographic variables and the surgical data were similar in the study groups. The patients in the MC group had higher elevation of the CRP mean values post-operatively (p = 0.01). However, the patients in the MC group had higher elevation of the IL-1ra mean values post-operatively, the mean pre-/post-operative IL-1ra values being 299/614 pg/ml in the MC group versus 379/439 pg/ml in the LC group (p = 0.003). There was no statistical significance in IL-6 mean values between the MC and LC groups pre- and post-operatively (POP1). However, the patients in the MC group had higher IL-6 mean values six hours post-operatively (POP2), the mean IL-6 values being 27.6 pg/ml in the MC group versus 14.8 pg/ml in the LC group (p = 0.037). In addition, the patients in the MC group had higher elevation of the IL-6 mean values post-operatively, the mean pre-/post-operative IL-6 values being 4.1/27.6 pg/ml in the MC group versus 3.8/14.8 pg/ml in the LC group (p = 0.04). There was no statistical significance in IL-8, IL-10, and IL-1β mean values between the MC and LC groups pre- and post-operatively.ConclusionOur results suggest that the inflammatory response in MC versus LC groups was similar based on the IL-8, IL-10, and IL-1β values. A new finding with possible clinical relevance in the present work is higher relative elevation of the IL-1ra and IL-6 mean values post-operatively in the MC group. [ABSTRACT FROM PUBLISHER]

Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 μg/d, or 80 μg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25–35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background: Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism. Methods: A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit. Results: Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment. Conclusion: IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology. [ABSTRACT FROM AUTHOR]

Neutropenic fever is common in patients receiving intensive chemotherapy for hematological malignancies. The clinical course may be aggravated by infectious complications like severe sepsis, septic shock or even death. We prospectively studied 100 patients with neutropenic fever and evaluated human plasma cell-free DNA (cfDNA) during the fi rst 3 days after the onset of fever as a prognostic biomarker for complicated clinical course, defined as sepsis or septic shock. Complicated course was observed in 21 patients (21%). There were no significant differences in cfDNA levels between the patients with or without complications on any study day when all the patients were analyzed as one group. In subgroups according to hematological malignancy, patients with acute myeloid leukemia (AML) had lower cfDNA levels than patients with lymphoma. Among AML patients d0 cfDNA/leukocyte ratio and among lymphoma patients d0 cfDNA was associated with subsequent development of sepsis or septic shock. cfDNA deserves further studies in hematological patients with sepsis. [ABSTRACT FROM AUTHOR]

Introduction Low first-trimester serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) predict later preeclampsia. We studied whether serum hCG-h at 14-17 weeks of pregnancy also predicts preeclampsia alone or combined with placental growth factor (PlGF) and soluble vascular endothelial growth factor 1 (sVEGFR-1). Methods We conducted a nested case-control study comprising 55 women with subsequent preeclampsia, 21 with gestational hypertension, 30 with a small-for-gestational-age infant, and 83 controls. Serum concentrations of hCG-h, proportion of hCG-h to hCG (%hCG-h), PlGF, and sVEGFR-1 were converted to multiples of the medians (MoMs) adjusted for gestational age. Results Concentrations of hCG-h or%hCG-h did not differ between women with subsequent preeclampsia and controls. In women with subsequent preeclampsia, PlGF was lower (0.62MoM) than in controls (P<0.001). In receiver-operating characteristics curve analysis for the prediction of preeclampsia, the area under the curve for hCG-h or %hCG-h was not significantly different from 0.5, whereas that for PlGF was 0.746 (95% confidence interval, 0.656-0.836; P<0.001). Combining hCG-h or %hCG-h with PlGF did not improve the prognostic value. Conclusions Serum hCG-h did not improve prediction of preeclampsia in the second trimester. [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.

Vitamin D deficiency has been associated with an increased risk of developing a number of diseases. Here we investigated samples from 71 pre-diabetic individuals of the VitDmet study, a 5-month high dose vitamin D3 intervention trial during Finnish winter, for their changes in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations and the expression of primary vitamin D target genes in peripheral blood mononuclear cells and adipose tissue. A negative correlation between serum concentrations of parathyroid hormone and 25(OH)D3 suggested an overall normal physiological vitamin D response among the participants. The genes CD14 and thrombomodulin (THBD) are up-regulated primary vitamin D targets and showed to be suitable gene expression markers for vitamin D signaling in both primary tissues. However, in a ranking of the samples concerning their expected response to vitamin D only the top half showed a positive correlation between the changes of CD14 or THBD mRNA and serum 25(OH)D3 concentrations. Interestingly, this categorization allows unmasking a negative correlation between changes in serum concentrations of 25(OH)D3 and the inflammation marker interleukin 6. We propose the genes CD14 and THBD as transcriptomic biomarkers, from which the effects of a vitamin D3 supplementation can be evaluated. These biomarkers allow the classification of subjects into those, who might benefit from a vitamin D3 supplementation, and others who do not. [ABSTRACT FROM AUTHOR]

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]

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8-9 a.m. on days 1-4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at assessing the cut-off levels for pentraxin 3 (PTX3) in predicting complications of neutropenic fever (bacteraemia, septic shock) in haematological patients. Methods: A prospective study during 2006-2009 was performed at haematology ward in Kuopio University Hospital. A patient was eligible for the study if having neutropenic fever after intensive therapy for acute myeloid leukaemia (AML) ( n = 32) or non-Hodgkin lymphoma (NHL) ( n = 35). Blood cultures were taken, and maximal PTX3 and C-reactive protein (CRP) were evaluated during d0 to d3 from the beginning of fever onset. Results: The level of PTX3 was associated with both the underlying malignancy and the presence of complications, with highest level in NHL patients with complicated course of febrile neutropenia and lowest in AML patients with non-complicated course. The cut-off level of PTX3 to predict complications was ten-fold in patients with NHL (115 μg/L) in comparison with patients with AML (11.5 μg/L). In combined analysis based on separate cut-offs, PTX3 predicted complications of febrile neutropenia with sensitivity of 0.86, specificity of 0.83, positive predictive value of 0.57 and negative predictive value of 0.96. Conclusions: PTX3 was superior to CRP in predicting complicated course of febrile neutropenia, but only when the effect of the underlying malignancy had been taken into account. [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]